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View all the figures for this chapter.

Upper Endoscopy

Editor: Joseph Sung


9. Enteroscopy and capsule endoscopy

John Morris

Top of page Introduction  Next section

The length and tortuous nature of the small intestine has constituted a considerable challenge for endoscopic practice. However, certain techniques are now well established. Three methods have dominated the field since the first enteroscopes were developed more than 30 years ago.

  • Sonde enteroscopy (a thin floppy scope with a balloon tip)
  • Push enteroscopy (a long standard endoscope)
  • Intraoperative enteroscopy (endoscopy during surgery)

Recently, the field has been revolutionized by the development of wireless capsule endoscopy.

We here review technical developments, diagnostic results, and the outcomes of therapeutic interventions, particularly in patients with obscure gastrointestinal bleeding. Important new information on the clinical application and early results for capsule endoscopy are now available, and are certain to stimulate further research in this dynamic field.

Top of page Techniques  Previous section Next section

Sonde enteroscopy  Previous section Next section

The Sonde endoscopy method is now mainly of historical interest, but it is worth reviewing, not least because there are important lessons for gastroenterologists now working with the capsule.

The sonde enteroscope is long (2.7 m), and thin (0.5 cm in diameter), with an inflatable balloon at the tip [1–4]. It is usually passed through the nose, and advances by the passive propulsive effects of small bowel peristalsis (Fig. 1). The jejunum and ileum are examined on withdrawal, but the method has significant problems. It takes several hours, and is often poorly tolerated. Visualization is limited due to lack of tip deflection, and the uncontrolled nature of withdrawal results in incomplete visualization. For these reasons, Sonde enteroscopy never established a place in routine clinical practice, other than in a few units with a particular interest in patients with obscure bleeding. Nevertheless, the technique did show that endoscopic examination of the small bowel was possible, and indeed clinically desirable. Reports of diagnostic yields superior to conventional radiological techniques emphasized the importance of diseases of the jejunum and ileum, and the need to develop more reliable methods for diagnosis and therapy [5,6].

Push enteroscopy  Previous section Next section

Push enteroscopy is well established in clinical practice. Enteroscopes are essentially long floppy forward-viewing scopes, 2.2–2.5 m in length. Initial experience was reported using colonoscopes passed orally [7–13]. Preparation and sedation are the same as for standard upper endoscopy. Once the tip of the scope is in the descending duodenum, a stiffening overtube can be deployed to reduce gastric looping, which is a major factor limiting the duct through insertion. Even so, the tip of the endoscope rarely reaches beyond the first 50–70 cm beyond the pylorus. Usually, antispasmodic agents are avoided until the withdrawal/inspection phase of the examination.

Depth of insertion  Previous section Next section

Using a longer enteroscope does not seem to increase the insertion depth predictably. A stiffening overtube can help, but the overall value of this technique is still in dispute, not least because its use has resulted in significant complications [14–19].

Newer methods to improve the intubation depth include utilizing a double balloon method to create a concertina effect. Total small bowel intubation can be achieved and the ability to biopsy or deliver therapy are likely to be of particular interest as an alternative to operation in patients with small bowel lesions found at capsule endoscopy [20,21]

Accurate measurement of the insertion depth is challenging. We simply pull the enteroscope back until the tip starts to withdraw. This gives a reasonably reliable measurement, which is used to guide subsequent therapy.

Routine biopsy?  Previous section Next section

Routine biopsy is recommended when examining patients with suspected small bowel disease because there is a significant yield even with negative macroscopic views [22,23].

Intraoperative enteroscopy  Previous section Next section

The small bowel can be examined during laparotomy, using either a sterilized colonoscope passed through an enterotomy, or a push enteroscope passed through the mouth [24–28]. The surgeon 'milks' the intestine over the endoscope. Encouraging diagnostic yields have been observed, but the procedure is not without risk. Complications have been reported in up to a quarter of these procedures, including serosal tears, prolonged ileus, even an enterovaginal fistula [29,30,31]. Intraoperative enteroscopy has usually been employed as an intervention of last resort in patients with significant ongoing GI bleeding after full investigations, including push enteroscopy. The recurrent nature of bleeding from arteriovenous malformations in particular was a major disincentive to intraoperative interventions, especially segmental resections.

Laparoscopic-assisted enteroscopy [32]  Previous section Next section

This technique uses the peroral passage of a long push enteroscope or colonoscope, or even a Sonde enteroscope. The surgeon performs a standard diagnostic laparoscopy, and then uses laparoscopic instruments to help the endoscopist advance the enteroscope. Intubation of the terminal ileum has been described by this technique, but previous surgery and adhesions may interfere, and postoperative ileus has occurred [32].

Combined techniques  Previous section Next section

Lack of predictable deep insertion has led to the combining of push enteroscopy with colonoscopy and ileoscopy and combining enteroscopy with enteroclysis [33,34].

Capsule enteroscopy  Previous section Next section

This new technique involves the patient swallowing a wireless capsule camera which is 11 × 30 mm in length and consists of complimentary metal oxide silicon sensors (CMOS), an application specific integrated circuit (ASIC) device and white light emitting diode (LED) illumination(Fig. 2) No specific bowel preparation other than the overnight fast is needed. Some reports even suggest that capsule progression through the small intestine may be delayed by large bowel preparation (Fig. 3). The capsule images are transmitted at the rate of 2 per s to aerials positioned across the abdomen and stored in a recorder for subsequent analysis. The entire examination may obtain up to 50 000 images and battery life permits transmission for up to 6–8 h, during which patients are ambulant and independent [35]. Images are analyzed on a computer workstation. Problems with this technique include: the small risk of capsule impaction (in patients with unsuspected strictures); incomplete examination of the small bowel due to limited battery life in patients with prolonged small bowel transit (in up to 15% of patients); and the length of time it takes to review and analyze the recorded data (at least an hour in experienced hands).

Top of page Clinical applications of enteroscopy and capsule endoscopy  Previous section Next section

Enteroscopy and capsule techniques have been used for the investigation of patients with obscure gastrointestinal bleeding, suspected inflammatory bowel disease, malabsorption syndromes, and some rarities such as small bowel transplantation.

Obscure gastrointestinal bleeding  Previous section Next section

Definitions and prevalence  Previous section Next section

Gastrointestinal bleeding is defined as 'obscure' when patients continue to bleed despite normal upper and lower endoscopy examinations. This is not uncommon. Studies have shown that endoscopy and colonoscopy together reveal lesions in only just over one half of patients with documented iron deficiency anaemia [36,37]. The result was no higher in patients who also had positive fecal occult blood tests [38].

Multiple guidelines are available suggesting algorithms for the evaluation of this problem and defining the potential role of enteroscopy [39,40]. Patients with obscure gastrointestinal bleeding may be subdivided into those with overt (blood loss noticed by patient) and occult (unnoticed by patients) bleeding. Although such subdivision may seem arbitrary with inevitable overlaps, the appreciation that the rate of blood loss may influence diagnostic yield of enteroscopy will influence the enthusiasm for enteroscopy in such patients.

Historical estimates of the prevalence of small bowel lesions to account for blood loss have varied from 3% to 5% but these are undoubtedly underestimates resulting from lack of appropriate methods to evaluate the small bowel mucosa.

Alternative diagnostic procedures in obscure bleeding  Previous section Next section

Small bowel radiology, isotope-labeled red cell studies, and angiography have all been used in this context, but the diagnostic yield is low [41–44]. Newer imaging modalities such as helical CT angiography might improve the yield, but availability is currently limited [45].

When to use enteroscopy in obscure bleeding  Previous section Next section

Some clinicians question the need for further evaluation when endoscopy and colonoscopy are negative, since a number of series attest to the benign outcome of anaemia in this context [46–48]. This attitude fails to recognize the negative healthcare impact on the patient, and the significant resource implications of subsequent management [49]. It is our view that patients with more than a single unexplained episode of iron deficiency anaemia should undergo evaluation by enteroscopy or capsule endoscopy [50,51].

Pathology of obscure bleeding  Previous section Next section

Angiodysplasia and small bowel tumors are the commonest identified causes of obscure gastrointestinal bleeding (Fig. 4). Predominant tumor types are gastrointestinal stromal tumors (GIST), adenocarcinomas, and lymphomas (Figs 5 and 6). Secondary spread to the bowel from melanoma and lung cancer in particular can present as obscure gastrointestinal bleeding [52]. Whilst it is asserted that tumors frequently present in younger patients, our experience, particularly with a large population of patients with celiac disease, is that tumors are found equally in all age groups [53](Fig. 7). The superficial nature of angiodysplasia explains the disappointingly low diagnostic yield from non-endoscopic diagnostic methods. In approaching the management of a patient thought to be bleeding from angiodysplasia it is important to understand the likely geographic distributions, limited non-endoscopic treatment options and recurrent nature of these lesions, even if successfully treated initially by endoscopic methods or segmental resections. Angiodysplasias are most frequently found in the proximal jejunum and right colon and increase in frequency with age. The factors predisposing to this distribution are unknown, but suggestions include bowel wall surface tension. Recent data suggests that bleeding from angiodysplasia in some cases may be related to a deficiency of Von Willebrand factor, as these multimers promote hemostasis at very high shear conditions experienced in the gut wall related to vascular abnormalities [54]. Even if these lesions are treated, the persisting pathophysiological abnormalities mean that recurrence is almost inevitable. Clinicians should develop an expectation that further therapy may become necessary in the future. In attempting to allow objective assessment and comparison of treatment outcomes the European Club of Enteroscopy has proposed a classification of angiodysplasia which may be helpful in future studies [55].

Medical therapy for angiodysplasia  Previous section Next section

Non-endoscopic therapy of a diffuse and recurring disease would seem to have some theoretical advantages. Early reports of successful hormone therapy (estrogen/progesterone) in inherited vascular disorders [56] seemed to encourage more widespread use and some non-randomised cohort studies supported the use of hormone therapy in acquired angiodysplasia [57–59]. However, a significant number of patients on hormone therapy have to discontinue the medication due to unacceptable side-effects. Other reports of the use of vasoactive drugs such as Octreotide seemed equally encouraging [60,61] but in clinical practice non-endoscopic therapy has remained disappointing. In a recent important study from Spain no benefit of the use of hormone therapy to prevent bleeding from angiodysplasia was observed in a controlled study. At present hormone therapy cannot be recommended for acquired vascular malformations of the gut [62].

Diagnostic yield and outcomes of enteroscopic techniques in bleeding  Previous section Next section

In patients with obscure gastrointestinal bleeding/unexplained anaemia, three studies show remarkably similar diagnostic yield for sonde enteroscopy—26–30% [6,63,64]. New diseases have been identified, for example NSAID enteropathy, occurring in 47% of patients with unexplained anaemia receiving these drugs [65]. The rate of blood loss is a factor determining the diagnostic yield, which increases from 27% in patients with anaemia to 37% in those with acute bleeding [6]. Although the push examination is limited to the proximal jejunum, several series confirm the superior diagnostic yield of this procedure, compared with sonde enteroscopy, with diagnostic rates ranging from 30% to 64% depending on case selection [66–70]. This is probably a reflection of improved mucosal inspection as a result of a more controlled examination technique. Only one study has evaluated the combined diagnostic potential of push and sonde enteroscopy in the same patients giving a combined yield of 58% overall, with sonde enteroscopy adding an additional 26% of patients with a diagnosis achieved. This data confirms that depth of intubation is a key factor determining diagnostic yield of enteroscopy [71–73].

Comparing capsule and push enteroscopy  Previous section Next section

Comparisons of the capsule technique with standard push enteroscopy have (not surprisingly) shown increased yields from the capsule, not least because push enteroscopy rarely examines more than half of the small intestine. One study involved sewing colored beads into the small intestine of dogs. Sensitivities for push enteroscopy and capsule endoscopy were 37% and 64%, respectively. There is now a plethora of clinical studies indicating significant diagnostic yields in patients with obscure bleeding. However, the effect on clinical outcomes awaits further evaluation [74,75].

Diagnostic yields of 55% and 68% for the capsule examination are impressive [76–79]. However, the low diagnostic yield of push enteroscopy in comparative studies to date might reflect selection bias, as some patients already had a negative push enteroscopy [76].

Repeat standard endoscopies before enteroscopy?  Previous section Next section

Most studies of enteroscopy indicate that lesions are often found within the reach of standard upper endoscopy, bringing into question the quality of the initial endoscopic procedures [80]. This has led to the suggested strategy of using push enteroscopy as the first (upper) examination in patients with unexplained anaemia [81]. Unfortunately, lack of access and experience with push enteroscopy will make application of this strategy unlikely for most patients.

Unusual causes of obscure bleeding  Previous section Next section

The growing use of push enteroscopy in patients with bleeding has yielded many unusual diagnoses, including worm infestation, jejunal varices, ulceration related to Henoch Schonlein purpura, and bleeding from aortic graft fistula [82–85].

Enteroscopic therapy for bleeding  Previous section Next section

The push enteroscope allows delivery of endoscopic therapy, primarily through cauterization of arteriovenous malformations. Whilst retrospective studies show encouraging results, only one prospective study has addressed the impact of heater probe ablation in this clinical setting [86–88]. We found complete resolution of bleeding in 83% of patients with a significant improvement in hemoglobin levels [88]. Due to the thin small bowel wall we recommend a maximum of three 10 J applications of the heater probe to each arteriovenous malformation. Following initial ablation bleeding is often seen (Figs 8–10). Whilst the reduction of blood loss was confirmed in subsequent studies, an interesting effect on improved quality of life has also been demonstrated, probably as a result of reduced transfusion and hospitalization [89]. Interest in the long-term outcome of patients having investigation and treatment by push enteroscopy has revealed important insights into the perceived benefit of the procedure. Although enteroscopy was perceived by clinicians to have positively influenced patient management in three studies, in one of these studies only one third of the patients felt it was beneficial [90–92]. This discrepancy probably reflects the lack of impact to an individual patient of not achieving a diagnosis after enteroscopy although once again these studies demonstrated reduced hospitalization in patients in whom a diagnosis was achieved. Rebleeding occurs in approximately one third of all patients with obscure bleeding. The risk is less on long-term follow-up patients who have undergone negative push enteroscopy [93]. Patients should be counselled about the risk of rebleeding, and the potential need for further investigation and treatment.

Intraoperative enteroscopy for obscure bleeding  Previous section Next section

This procedure is normally reserved for those patients in whom bleeding persists despite negative push enteroscopy. In this highly selected group, studies using a colonoscope passed orally or via enterotomies reveal a diagnostic yield approaching 70–80% of patients [94–99]. The ability to examine the whole small bowel has led to the perception that intraoperative enteroscopy should be regarded as the gold standard for small bowel evaluation. The only study which has compared enteroscopy with intraoperative enteroscopy found that both procedures missed lesions, but that intraoperative enteroscopy had a higher sensitivity [100]. Most experts now use a push enteroscope through the mouth for intraoperative enteroscopy, not least because it obviates the need for opening the bowel.

Push enteroscopy or capsule endoscopy for bleeding?  Previous section Next section

The problem for the clinician nowadays is to decide whether to use capsule endoscopy as the next step following negative upper endoscopy and colonoscopy, or whether to use push enteroscopy first. The latter would be advantageous only if lesions were found and treated at enteroscopy. Although data from diagnostic yield would seem to favor the capsule no studies are yet available to definitely answer this question. As stated in a recent ASGE technical review, patient factors and local availability will be major determinants in this process [101].

Small intestinal mucosal diseases  Previous section Next section

Celiac disease  Previous section Next section

Celiac disease is usually diagnosed (and excluded) by standard endoscopic biopsy from the distal duodenum. Enteroscopy is rarely required for diagnosis, although two studies did suggest an increased yield over standard duodenal biopsy [102,103]. Push enteroscopy should be restricted for diagnostic purposes when there is strong suspicion, or when the disease is refractory to treatment. Under these circumstances enteroscopy allows detection of macroscopic abnormalities such as ulceration and lymphoma, and the ability to obtain biopsies for immunopathological analysis [104,105]. Identifying patients at particular risk for developing lymphoma is an exciting prospect. Several studies have reported on an abnormal immunophenotype in which intraepithelial lymphocytes in patients with refractory celiac disease express on intracytoplasmic CD3 positive CD8 negative staining pattern. The majority also had clonal intestinal TCR gamma gene rearrangements [106–108]. These findings were found to be highly suggestive of subsequent development of enteropathy-associated lymphoma in the latter study whereas those without these patterns had good responses to steroid and gluten withdrawal.

Crohn's disease  Previous section Next section

Enteroscopy is of value in selected patients with negative investigations when there is a high index of suspicion of Crohn's disease. Abnormalities and supporting histology have been reported in up to 50% of such patients [109]. Remarkably similar results are also observed in patients examined by capsule enteroscopy [110]. Therapeutic enteroscopy (e.g. balloon dilatation of strictures) has also been used successfully in patients with proximal Crohn's disease [111]. Enteroscopy has also been used during surgery for complications of Crohn's disease, and has often shown a high frequency of metachronous lesions [112–114]. However, these findings have not affected the outcome, but the situation might change with newer immunomodulating therapies.

Small bowel tumors  Previous section Next section

Tumors of the small intestine are relatively uncommon. They account for less than 2% of tumors of the gastrointestinal tract and can be very difficult to identify [115]. Many present with obscure bleeding, and patients undergo repeated investigations prior to definitive diagnosis. Malignant tumors, particularly adenocarcinoma, present early with weight loss, pain, perforation, or obstruction [116]. Sonde enteroscopy revealed tumors in about 5% of 258 patients investigated for obscure bleeding [5]. This frequency reflects the over-representation of tumor patients in a series of patients with no diagnosis by other diagnostic modalities. However it emphasizes the fact that serious diseases occur in this patient group and that enteroscopy should be considered an important addition to non-endoscopic methods of evaluation [117, 118]. A further role of enteroscopy has recently been defined in patients with small bowel polyps in Peutz–Jeghers syndrome. Using push enteroscopy and intraoperative enteroscopy successful surveillance and polypectomy have been performed, avoiding the need for emergency surgery for intestinal obstruction. Although relatively small numbers of patients have been reported, these early results provide encouragement for future development of a screening and monitoring role for enteroscopy [119–122].

Novel indications  Previous section Next section

Capsule endoscopy has not proven useful in evaluating unexplained abdominal pain [123]. Images from the transient passage through the esophagus were found in a recent study to be insufficient to evaluate for esophagitis or Barrett's esophagus [124]. It is clear that future enthusiasm for capsule endoscopy will lead to its evaluation in many novel diseases or anatomical areas.

Top of page Conclusion  Previous section Next section

Small bowel endoscopy has been developed and evaluated extensively over the past two decades. The techniques, diagnostic yield, and clinical outcomes have been defined. Initial scepticism over the need for endoscopic examination of the small intestine has been replaced by a recognition of the potential role that this technique fulfills in the management of patients with obscure bleeding, small intestinal mucosal diseases, and tumors. Newer techniques have improved diagnostic yield and patient tolerance and now it is important to acknowledge that complete endoscopic examination of the gastrointestinal tract is a clinical reality. As our methods become more reliable, enteroscopy research will move from defining the process of the techniques to evaluating their role in disease management. Capsule endoscopy has added substantial impetus to this process.

Top of page Outstanding issues and future trends  Previous section Next section

Capsule endoscopy heralds a new era for structural evaluation of the gastrointestinal tract.

Important questions that will need to be clarified are: refining techniques to maximize mucosal views; studies to define inter- and intraobserver variability; who should most appropriately read capsule studies; and outcomes for individual patient groups.

Although currently limited to examination of the small bowel, we should expect that modifications of capsule technology will lend themselves to total gastrointestinal visualization, perhaps by a steerable capsule.

Simple changes to capsule function including blood indicators which are in evolution will probably be supplemented by other abilities such as measuring physiological conditions including pH and motility.

These devices will revolutionize our approach to patients with mucosal disease and be used to monitor disease progress, outcomes of therapy (and possibly delivery of it) and be an ideal screening tool. It is likely that contrast radiology will become obsolete and diagnostic endoscopic procedures may be gradually replaced. Increased demand for therapy or biopsy of lesions detected by capsule will, for the present, maintain significant need for push enteroscopy.

Top of page References  Previous section

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103 Cuillerier, E, Landi, B & Cellier, C. Is push enteroscopy useful in patients with malabsorption of unclear origin. Am J Gastroenterol, 2001; 96 (7): 2103–6. PubMed

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109 Perez Cuadrado Macenile, R & Iglesias, J et al. Usefulness of oral video push enteroscopy in Crohn's disease. Endoscopy, 1997; 29: 745–7. PubMed

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Synopsis
Introduction
Diagnostic upper endoscopy
  Normal esophagus
   Hiatus and Z-line
   Glycogenic acanthosis
   Erythema
   GEJ variants
  Abnormal esophagus
   Erythematous areas and erosions
   Ulcers
   Strictures
   Hiatal hernia
Endoscopy in esophagitis
  Endoscopic staging of esophagitis
   Savary–Miller classification
   Hetzel–Dent classification
   MUSE classification
   Los Angeles classification
  Other lesions associated with GERD
   Schatzki's ring
   Mallory–Weiss tear
   Scleroderma
  Postoperative changes after fundoplication
  Endoscopic biopsy
  Chromoendoscopy in GERD
Endoscopic management of esophageal strictures
  Esophageal dilation
   Principles of esophageal dilation
   Mechanical dilation
   Pneumatic (balloon) dilation
   Techniques of dilation
   Dilation of distal esophageal (Schatzki's) rings
  Concomitant medical therapy for strictures
  Refractory strictures
   Intralesional injection of corticosteroids
   Other endoscopic methods for strictures
  Complications of esophageal stricture dilation
Endoscopic therapies for GERD
  Radiofrequency energy delivery (Stretta®)
   Stretta® technique
   Mechanisms of action
   Complications
  Endoscopic implantation of bulking agents
   Inert polymer microspheres
   Enteryx™
   Expandable hydrogel prosthesis (Gatekeeper™)
  Endoscopic plication systems
   Endoluminal gastric plication (ELGP)
   NDO
   Boston Scientific device
Outstanding issues and future trends
  Disclosure
References
Synopsis
  Barrett's esophagus
  Esophageal cancer
Barrett's esophagus
  Introduction
  Definition of Barrett's esophagus
   Long-segment Barrett's esophagus (LSBE)
   Short-segment BE (SSBE)
   Ultra-short BE (SSBE)
  Risk factors for Barrett's esophagus
   Gastroesophageal reflux disease (GERD)
   H.pylori and GERD
   Age, sex, and race
   Other risk factors
  Epidemiology of Barrett's esophagus
  Natural history of Barrett's esophagus
  Pathogenesis of Barrett's esophagus
   Acid
   Bile
   Helicobacter pylori
  Novel diagnostic techniques for Barrett's esophagus
   Introduction
   Chromoendoscopy
   Magnification/high-resolution endoscopy
   Other investigational techniques
   Endoscopic ultrasonography (EUS)
   Light induced fluorescence (LIF)
   Optical coherence tomography (OCT)
   Reflectance and elastic light scattering spectroscopy
   Confocal microscopy
   Raman spectroscopy (RS)
  Screening for Barrett's esophagus
   Rationale
   Esophagogastroduodenoscopy (EGD)
  Diagnosis of Barrett's esophagus
  Management of Barrett's esophagus
   Surveillance
   Rationale
   Procedure/techniques
   Utility of surveillance
   Chemoprevention of Barrett's esopahgus
   Medical reduction of acid load
   Endoscopic therapy for Barrett's esophagus
   Thermal ablation: Monopolar/bipolar/heater probe electrocoagulation
   Photodynamic therapy (PDT)
   Endoscopic mucosal resection (EMR)
   Surgery for Barrett's esophagus
  Barrett's esophagus conclusion
Esophageal cancer
  Introduction
  Risk factors for esophageal cancer
  Epidemiology of esophageal cancer
  Natural history of esophageal cancer
  Diagnosis of esophageal cancer
   Clinical features
   Laboratory data
   Radiology
   Endoscopy
   Staging
  Management of esophageal cancer
   Endoscopy
   Ablative techniques
   Endoscopic mucosal resection (EMR)
   Endoscopic dilation
   Injection therapy (EIT)
   Esophageal endoprosthesis (EE)
   Surgery for esophageal cancer
   Radiation therapy for esphageal cancer
   Chemotherapy for esophageal cancer
  Esophageal cancer conclusion
  Outstanding issue and future trends
References
Synopsis
  Diagnostic methods
   Endoscopy
   Endoscopy, when and where?
   Lavage before endoscopy?
   Ulcer stigmata
   Removing clots?
Endoscopic hemostasis
  Available techniques
  Injection hemostasis
  Thermal methods
  Combination methods
Care after bleeding
  Diet
  Acid suppression
  H.Pylori
  Aspirin and NSAIDs
  Discharge
Rebleeding
  Early rebleeding
  Predictors of rebleeding
   Ulcer stigmata
  Prevention of rebleeding
  Treatment of rebleeding
  Late rebleeding
   H.pylori
   NSAIDs and aspirin
   Acid suppression
Non-ulcer bleeding
Issues and future trends
  New suturing devices, clips, and bands
  Visualization (scope size)
  Airway protection/anesthesia
  Training
References
Synopsis
Background
National history of variceal bleeding
  Mechanism of bleeding
   Variceal stigmata
  Risk of bleeding
  Prognostic indices
  Rebleeding
Endoscopy: general
Endoscopic treatments
  Endoscopic injection sclerotherapy (EST)
  EST technique
   Sclerosants
   Accessory devices
   Post-EST care
   EST—proof of value?
  Endoscopic variceal ligation (EVL)
   Multi-fire devices
   Recurrence
  Comparing EST and EVL
   Cyanoacrylate (Histoacryl®) injection
  Complications of EST and EVL
  Detachable mini-snare
   Technique
   Results
Treatment of ACUTE variceal hemorrhage
  Pharmacological treatments
  Combined endoscopic and pharmacological therapy
  Surgery
  Tipss
   Comparing TIPSS with endoscopic treatments
  Consensus approach to acute bleeding
  Combined endoscopic therapies vs. single therapy
   Synchronous combinations
   Metachronous combinations
Prophylactic treatment of esophageal varices
  Detection and surveillance
  Endoscopic prophylaxis
Gastric varices
Endoscopic ultrasonography in variceal hemorrhage
  EUS and gastric varices
Outstanding issues and future trends
References
Synopsis
Introduction
Gastritis
  H.pylori-associated gastritis
  Gastritis: clinical manifestations and symptoms
Ulcer disease
  H.pylori and ulcers
  H.pylori: the pathogenetic pathway
   Pattern and phenotype of gastritis in association with H. pylori
   Alterations in the homeostasis of gastric hormones and acid secretion related to H. pylori
   Gastric metaplasia in the duodenum is a prerequisite for H. pylori colonization
   Interaction of H. pylori with the mucosal barrier
   Ulcerogenic strains of H. pylori
   Genetic factors and H. pylori
   The therapeutic proof of causality: H. pylori and ulcers
  Ulcers: clinical features and diagnosis
   Test and treat
   Endoscopic diagnosis
Treatment of peptic ulcers
  Acid suppression
  H.pylori eradication
NSAIDs and gastrointestinal pathology
  Introduction
  Clinical and histological characteristics of NSAID-related injury
  Epidemiology of NSAIDs and gastric injury
  Risk modifiers of injury with NSAIDs
   Dosage and type of NSAID
   Age
   Prior ulcer
   Anticoagulants
   Corticosteroids
   H.pylori infection and NSAIDs combined
  Management of NSAID-associated gastrointestinal toxicity
   Selective COX-2 inhibitors
   Prophylaxis against NSAID injury
Conclusion
  H.pylori
  NSAIDs
  Prophylaxis
Outstanding issues and future trends
References
Synopsis
Definitions
  Gastric carcinoma
  Premalignant gastric lesions
  Gastric polyps as premalignant lesions
   Adenomatous polyps
   Cystic fundic polyps
   Hyperplastic or hyperplasiogenic polyps
   Fibro-inflammatory polyps
   Hamartomas and juvenile polyps
   Other polyps
  Premalignant conditions in the gastric mucosa
   Carditis
   Chronic atrophic gastritis
Histopathological classification of gastric neoplasia
  TNM classification
  Vienna classification
Epidemiology
  Geographical variations of risk
  Proximal and distal gastric cancer
  Causal factors
   Cancer at the EG junction
   Cancer in the distal or non-cardia stomach
  Time trends in incidence and mortality from gastric cancer
   A generalized decline of the disease
   Time trends in Japan
Gastric carcinogenesis
  From inflammation to cancer
  The APC mutation in gastric carcinogenesis
  Mutagenesis in the Lauren classification
  Hereditary gastric cancer
Symptoms of gastric cancer
Endoscopy in the diagnosis of gastric cancer
  Methods
   At the EG junction
   In the non-cardia stomach
  Technological advances in equipment
   Magnification
   Digitization of the image
   Spectroscopic techniques
  Macroscopic appearance of digestive neoplastic lesions
  Endoscopic classification of superficial neoplastic gastric lesions
   At the EG junction
   In the non-cardia stomach
Non-endoscopic procedures in the diagnosis of gastric cancer
  Radiological imaging and ultrasound
  Molecular biology
   Proliferative indices
   P53 protein and TP53 mutations
   Cytokeratins
   Mucins
  Staging of gastric cancer
Clinical relevance of early diagnosis of gastric cancer
Treatment decisions for gastric cancer
  The role of tumor staging
  Treatment with curative intent
  Other therapeutic options
Endoscopic treatment with curative intent
  Technique of endoscopic mucosal resection (EMR)
   EMR with a cap [97]: EMR-C (aspiration method)
   EMR with a ligating cap [102]: EMR-L (aspiration method)
   EMR with tissue incision [103,105,107,108]
   EMR grasp-method [100,103]
  Indications for EMR
  Results and complications of EMR
Surgery for gastric cancer
  Lymphadenectomy
  Extent of the resection
  Palliative gastrectomy
Chemoradiation in advanced gastric cancer
  Chemoradiation protocols (palliation)
  Adjuvant chemoradiation protocols
Endoscopic palliation with Nd:YAG laser
Endoscopic palliation with stents
  Types of stents
  Placement of the stent and indications
  Results and complications of stenting
   Results at the EG junction
   Results at the gastric outlet
   Complications
Guidelines in surveillance
Prevention of gastric cancer
  Prevention and H. pylori infection
  Prevention through dietary intervention
  Unplanned prevention
Secondary prevention of gastric cancer
  Gastroscopy and opportunistic screening
  Mass screening
   In Japan
   In other countries
   Strategy of detection worldwide
References
Synopsis
Introduction
  Benefits of nutrition support
  Enteral access
Gastric or enteric feeding?
Nasogastric (NG) feeding
  NG tube placement
  NG tube management
  NG tube complications
Nasojejunal (NJ) feeding
  Technique
   Different tubes
   Prokinetics
   Fluoroscopy or endoscopic assistance
   The drag technique
   Through the scope passage
  NJ tube management
  NJ tube feeding complications
   Bronchial misplacement
Percutaneous endoscopic gastrostomy (PEG)
  Indications
   Cancer patients
   Stroke
   Dementia
  Contraindications
  PEG technique
  PEG tube management
   Feeding
   Diarrhea
  Complications of PEG
   Tube dislodgement
Percutaneous endoscopy gastrostomy/jejunostomy (PEG/J)
  Indications/contraindications
  J tube placement through a PEG (PEG/J)
  PEG/J tube management
  Complications of PEG/J tubes
Direct percutaneous endoscopic jejunostomy (DPEJ)
  Indications/contraindications
  DPEJ technique
  DPEJ tube management
  DPEJ tube complications
Enteral formulations
  Blenderized formulations
  Lactose-containing formulations
  Lactose-free formulations
  Elemental formulations
  Specialty formulations
  Modular feedings
  Supplemental regimes
  Immune enhancing diets (IED)
Conclusions
Outstanding issues and future trends
References
Introduction
Techniques
  Sonde enteroscopy
  Push enteroscopy
   Depth of insertion
   Routine biopsy?
  Intraoperative enteroscopy
   Laparoscopic-assisted enteroscopy [32]
   Combined techniques
  Capsule enteroscopy
Clinical applications of enteroscopy and capsule endoscopy
  Obscure gastrointestinal bleeding
   Definitions and prevalence
   Alternative diagnostic procedures in obscure bleeding
   When to use enteroscopy in obscure bleeding
   Pathology of obscure bleeding
   Medical therapy for angiodysplasia
   Diagnostic yield and outcomes of enteroscopic techniques in bleeding
   Comparing capsule and push enteroscopy
   Repeat standard endoscopies before enteroscopy?
   Unusual causes of obscure bleeding
   Enteroscopic therapy for bleeding
   Intraoperative enteroscopy for obscure bleeding
   Push enteroscopy or capsule endoscopy for bleeding?
  Small intestinal mucosal diseases
   Celiac disease
   Crohn's disease
  Small bowel tumors
  Novel indications
Conclusion
Outstanding issues and future trends
References

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