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Biomedical subjects

J Haringsma

Publications and source records attributed to J Haringsma.

At least 19 recordsLinked to original sources

Oesophagitis is common in patients with achalasia after pneumatic dilatation.

BACKGROUND: Achalasia, an oesophageal motor disease, is associated with functional oesophageal obstruction. Food stasis can predispose for oesophagitis. Treatment aims at lowering of the lower oesophageal sphincter pressure, enhancing the risk of gastro-oesophageal reflux. Nevertheless, the incidence of oesophagitis after achalasia treatment is unknown. AIM: To investigate the incidence and severity of oesophagitis in achalasia patients treated with pneumatic dilatation. METHODS: A cohort of 331 patients with achalasia were treated with pneumatic dilatation and followed. Oesophagitis and stasis were assessed by endoscopy and inflammation was graded by histology. RESULTS: 251 patients were followed for a mean values of 8.4 years (range: 1-26). The average number of endoscopies with biopsy sample sets per patient was 4 (range: 1-17). Three patients had no histological signs of oesophagitis throughout follow-up, 139 had oesophagitis grade 1, 49 oesophagitis grade 2 and 60 grade 3. Specialized intestinal metaplasia was found in 37 patients. The association between endoscopic food stasis and histological inflammation was significant. The association between endoscopic signs of oesophagitis and histological inflammation was poor. CONCLUSIONS: Forty percent of the achalasia patients develop chronic active or ulcerating oesophagitis after treatment. Inflammation was associated with food stasis. Because the sensitivity of endoscopy to detect inflammation is low, surveillance endoscopy with biopsy sampling and assessment of stasis is warranted to detect early neoplastic changes.

Adolescent↗

Acute pancreatitis after double-balloon enteroscopy: an old pathogenetic theory revisited as a result of using a new endoscopic tool.

Double-balloon enteroscopy is a novel technique for visualizing the entire small bowel. Complications have been reported relatively rarely in the small series published up until now. In this report we describe two patients who developed acute pancreatitis immediately after double-balloon enteroscopy, diagnosed on clinical, biochemical, and radiological grounds. In both patients the pancreatitis resolved with supportive care. Based on early studies on the pathogenesis of acute pancreatitis, we discuss the possible pathogenetic mechanism for pancreatitis arising as a complication of this novel endoscopic technique.

Acute Disease↗

Diagnostic and therapeutic endoscopy.

Within the gastrointestinal tract, there is no shorter segment with a higher cancer incidence than the gastro-esophageal junction. Flexible endoscopy is the mainstay for diagnosis of early and advanced esophageal adenocarcinoma, for the treatment of early lesions, and also for the palliation of advanced cancer. New developments in endoscopy aim to improve the diagnosis and treatment of esophageal cancer. These include high resolution and magnification endoscopy in combination with chromendoscopy, and techniques based on modulation of the features of light bundles, such as narrow band imaging, fluorescence endoscopy, and elastic scattering spectroscopy. The value of these techniques for the surveillance of distal esophageal neoplasia needs further study. Furthermore, new methods of tissue sampling and evaluation are being studied to augment identification and staging of patients at risk for cancer. Finally, newer instruments may decrease patient burden during endoscopy, making screening and surveillance more acceptable from a patient's perspective. This review discusses the new developments in flexible endoscopy for diagnosis and therapy of early and advanced and advanced esophageal adenocarcinoma.

Adenocarcinoma↗

Causes and treatment of recurrent dysphagia after self-expanding metal stent placement for palliation of esophageal carcinoma.

BACKGROUND AND STUDY AIMS: Recurrent dysphagia frequently complicates the palliative treatment of esophageal cancer with self-expanding metal stents. Strategies for repeat interventions and subsequent outcomes have not been adequately reported to date. PATIENTS AND METHODS: A total of 216 patients underwent placement of a self-expanding metal stent (Ultraflex, n = 75; Flamingo Wallstent, n = 71; Z-stent, n = 70) for malignant dysphagia, and were followed up prospectively. The causes of stent-related recurrent dysphagia, the intervals after first stent placement, and the procedures used for repeat intervention and their outcomes were evaluated. RESULTS: Seventy-four episodes of stent-related recurrent dysphagia occurred in 63 patients (29 %), mainly due to tumor overgrowth (n = 30; median 129 days), stent migration (n = 26; median 92 days) and food bolus obstruction (n = 16; median 80 days). Stent migration occurred more frequently ( P = 0.05), whereas tumor overgrowth occurred less frequently ( P = 0.05) with Ultraflex stents in comparison with Flamingo Wallstents and Z-stents. Tumor overgrowth was treated in 25 patients mainly by a second stent (n = 19) and was effective in 23 of the 25 patients (92 %). Five patients received no further treatment. Stent migration was treated by placing a second stent (n = 14), repositioning the migrated stent (n = 7), other treatments (n = 3), or no further treatment (n = 2), and treatment was effective in 20 of 24 (83 %) patients. Food bolus obstruction was treated by endoscopic stent clearance in all patients. Repeat intervention for stent-related recurrent dysphagia improved the dysphagia score from a median of 3 to 1 ( P < 0.001). The median survival period after repeat treatment was 68 days. CONCLUSIONS: Recurrent dysphagia occurs in almost one-third of patients after stent placement. Repeat interventions for stent-related recurrent dysphagia are effective in over 90 % of patients. New innovations in stent design are needed to reduce the risk of stent-related recurrent dysphagia.

Adenocarcinoma↗

5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett's oesophagus: a randomised trial.

BACKGROUND: Photochemical and thermal methods are used for ablating Barrett's oesophagus (BO). The aim of this study was to compare 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) with argon plasma coagulation (APC) with respect to complete reversal of BO. METHODS: Patients with BO (32 no dysplasia and eight low grade dysplasia) were randomised to one of three treatments: (a) ALA-PDT as a single dose of 100 J/cm(2) at four hours (PDT100; n = 13); (b) ALA-PDT as a fractionated dose of 20 and 100 J/cm(2) at one and four hours, respectively (PDT20+100; n = 13); or (c) APC at a power setting of 65 W in two sessions (APC; n = 14). If complete elimination of BO was not achieved by the designated treatment, the remaining BO was treated by a maximum of two sessions of APC. RESULTS: Mean endoscopic reduction of BO at six weeks was 51% (range 20-100%) in the PDT100 group, 86% (range 0-100%) in the PDT20+100 group, and 93% (range 40-100%) in the APC group (PDT100 v PDT20+100, p<0.005; PDT100 v APC, p<0.005; and PDT20+100 v APC, NS) with histologically complete ablation in 1/13 (8%) patients in the PDT100 group, 4/12 (33%) in the PDT20+100 group, and 5/14 (36%) in the APC group (NS). Remaining BO was additionally treated with APC in 23/40 (58%) patients. Histological examination at 12 months revealed complete ablation in 9/11 (82%) patients in the PDT100 group, in 9/10 (90%) patients in the PDT20+100 group, and in 8/12 (67%) patients in the APC group (NS). At 12 months, no dysplasia was detected. Side effects (that is, pain (p<0.01), and nausea and vomiting (p<0.05)) and elevated liver transaminases (p<0.01) were more common after PDT than APC therapy. One patient died three days after treatment with PDT, presumably from cardiac arrhythmia. CONCLUSION: APC alone or ALA-PDT in combination with APC can lead to complete reversal of Barrett's epithelium in at least two thirds of patients when administered in multiple treatment sessions. As the goal of treatment should be complete reversal of Barrett's epithelium, we do not recommend these techniques for the prophylactic ablation of BO.

Aged↗

The homeodomain protein CDX2 is an early marker of Barrett's oesophagus.

BACKGROUND: In Barrett's oesophagus (BO), squamous epithelium is replaced by specialised intestinal epithelium (SIE). Transcription factors associated with intestinal differentiation, such as CDX2, may be involved in BO development. AIM: To investigate CDX2 expression in BO, squamous epithelium, and oesophageal adenocarcinoma (ADC). METHODS: CDX2 expression was assessed in 245 samples-167 biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39 patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20 patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2 protein was investigated immunohistochemically in 138 biopsies from 16 patients with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO patients, and when present from ADC. RESULTS: SIE was present in 53/79 biopsies from the columnar lined segment; CDX2 protein was seen in all epithelial cells, but not in biopsies containing only gastric metaplastic epithelium (26/79), or in squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all biopsies with goblet cell specific Muc2 transcription-indicative of SIE. Low Cdx2 mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the squamocolumnar junction of BO patients. CONCLUSION: CDX2 protein/mRNA is strongly associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing squamous epithelium of one third of BO patients, and may precede morphological changes seen in BO. Therefore, pathways that induce Cdx2 transcription in squamous epithelial cells may be important in BO development.

Adenocarcinoma↗

MUC4 is increased in high grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio.

BACKGROUND: Patients with Barrett's oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. AIMS: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. METHODS: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett's epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1-4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. RESULTS: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. CONCLUSIONS: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.

Adenocarcinoma↗

Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions.

INTRODUCTION: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed dilatation of intercellular spaces with regard to: (1) interobserver variability, and (2) whether the incidence of this varies between 'red streaks' and the adjacent normal looking squamous epithelium. METHODS: Esophageal biopsies from 44 patients with chronic gastro-esophageal reflux (GERD) were evaluated. At endoscopy, these patients had one or more red streaks on the tops of the mucosal folds in the distal esophagus. Biopsies were taken from the red streaks and from the normal-appearing mucosa 1 cm lateral to the red streaks. Biopsies were assessed in a blinded fashion by two independent pathologists (MV & RF). Criteria for assessing intercellular space dilatation were evaluated and agreed on prior to the study. RESULTS: Good interobserver agreement was recorded (kappa = 0.82 at the streaks and 0.77 for the control tissues) for absence/presence of intercellular space dilatation. Red streak and control biopsies differed significantly (p = 0.0001), with respect to presence of dilated intercellular spaces, with 90.5 % of the former demonstrating this as present compared to 56.1% in the controls. CONCLUSION: This study supports the concept that esophageal mucosal minimal changes due to reflux is localised and that dilatation of intercellular spaces is an early sign of reflux-induced epithelial damage. The low interobserver variability in the assessment of intercellular space dilatation suggests that this may be a useful variable for assessment of early signs of acid-reflux induced damage to the squamous epithelium of the esophagus by use of light microscopy.

Biopsy↗

Endoscopic treatment of gastro-oesophageal reflux disease: the new kid on the block.

BACKGROUND: Gastro-oesophageal reflux disease is a common disease entity with approximately 7% of European adults experiencing significant daily symptoms. The impact of reflux disease on the quality of life is considerable. Complications of reflux disease include oesophagitis, stricture, Barrett's and pulmonary symptoms. Most patients can be adequately managed by treatment with a proton-pump inhibitor. However, symptom relapse is common after cessation of therapy, thus many patients are committed to life-long therapy. Until recently, anti-reflux surgery was the single therapeutic alternative. Now, novel endoscopic techniques have become available to treat patients suffering from reflux disease. Application of these techniques is challenging. METHODS: Update on new endoscopic techniques for treatment of reflux discase. RESULTS: Currently available endoscopic techniques include endoscopic suturing, radiofrequency ablation and biopolymer injection. Interventions typically take 30-40 min and can be performed under conscious sedation. First reports describe successful reduction of symptoms. Six months after therapy. reportedly 58%-85% of patients are off proton-pump inhibition. Yet, there are conflicting results on 24-h pH measurement and insufficient data on the mechanism of altered oesophageal motility. Long-term data are not yet available. In our series of over 50 procedures, no serious complications have occurred. CONCLUSIONS: Endoscopic treatment of reflux disease is feasible and safe. Techniques reduce both symptoms and medication use associated with the disease, albeit with an uncertain long-term outcome. As pursuit of this technology is appealing, techniques are being introduced before thorough comparison and evaluation of therapeutic benefit have been completed. Comparative studies between conventional anti-reflux treatment and various luminal anti-reflux therapies are needed and long-term efficacy remains to be established.

Adult↗

Barrett's oesophagus: new diagnostic and therapeutic techniques.

BACKGROUND: Barrett's oesophagus is associated with an increased risk of developing adenocarcinoma. Cancer development is preceded by dysplastic changes. Yet, detection of these microscopic changes has remained beyond the reach of routine endoscopy. Endoscopic screening in Barrett's therefore relies mainly on extensive random biopsy sampling. METHODS: Update on new endoscopic diagnostics techniques for Barrett's oesophagus. RESULTS: Application of new optical techniques has the potential to enhance our ability to detect dysplasia during endoscopic procedures and take targeted biopsies. Spectral information can be obtained either by point measurements using an optical fibre ('spectral biopsy') or by imaging a broad tissue field. Light-induced fluorescence techniques are based on the observation that tissue when excited by light of shorter wavelength will emit fluorescent light of a longer wavelength. This concept can be used to image tissue in vivo, based on minimal biochemical and structural changes of the (sub)mucosa. Elastic scattering spectroscopy is a spectral biopsy technique that can be exploited even to detect low-grade dysplasia, based on structural information of the mucosa, in which the size and crowding of nuclei in the epithelial layer play a key role. Optical coherence tomography uses reflection of light at optically scattering structures for cross-sectional tissue imaging. Compared to B-scan ultrasonography, optical coherence tomography offers a much higher resolution (10-20 micron), without the need for tissue contact or acoustic coupling. These spectral techniques, although still in their infancy, have already shown the ability to detect early cancer, high-grade dysplasia and in some cases even low-grade dysplasia with a promising degree of sensitivity. As the instruments and the techniques will be further refined, they are likely to become an important part of endoscopic screening. Advances in endoscopic treatment techniques make early malignancies, for which surgical resection is the only accepted therapy, amenable for minimally invasive endoscopic treatment. Endoscopic mucosal resection is a minimally invasive endoscopic technique that can be used in patients with circumscribed mucosal carcinomas. The technique is also useful as a diagnostic procedure by obtaining a full-thickness mucosal specimen for histologic examination. Photodynamic therapy using the prodrug 5-aminolevulinic acid is an ablative therapy that destroys the oesophageal mucosa, leaving the deeper layers of the oesophageal wall intact. Cell damage is achieved by the action of light on the photosensitizing agent protoporphyrin IX in the mucosa, with skin photosensitivity of less than 48 h. Such mucosal ablation, however, can also be accomplished with more common thermal techniques like argon plasma coagulation. In all these ablative procedures, squamous regeneration is obtained by rigorous antacid therapy. In selected patients, these endoscopic ablation methods, although still experimental, might already offer an alternative to oesophagectomy. The need for further improvement, in conjunction with the lack of long-term follow-up data, however, limits the use of these techniques to expert centres. CONCLUSION: New endoscopic techniques are likely to change the diagnostic and therapeutic procedures for Barrett's oesophagus in the near future.

Barrett Esophagus↗

Comprehensive Cancer Centre Amsterdam Barrett Advisory Committee: first results.

BACKGROUND: Treatment and follow-up policy for Barrett's oesophagus are dependent on the grade of dysplasia. However, sampling error of random biopsy protocols and subjectivity of pathological grading may hamper endoscopic surveillance. METHODS: The Amsterdam Comprehensive Cancer Center Barrett Advisory Committee (BAC) is a regional multidisciplinary consultative working-group, offering revision of pathology, revision of pathology plus additional endoscopic diagnostics, or referral for treatment. RESULTS: Between July 1998 and July 1999 30 patients were referred to the B.A.C for advice; eighteen patients were referred because of suspicion of high grade dysplasia. Reassessment of biopsies, including additional quantitative pathology, with or without additional endoscopic diagnostics, led to adjustment of the grading of dysplasia in 15 patients (50%). A suspicion of low grade dysplasia was rejected in nine out of ten cases. Adjustment of the original diagnosis often influenced further therapy or follow-up. CONCLUSIONS: reassessment of conventional pathology, quantitative pathology, and additional diagnostic procedures might improve the accuracy of diagnosis and staging of malignant degeneration of Barrett's oesophagus, although experience is still limited. The complexity of the management of these patients demands a specialised multidisciplinary approach. A Barrett Advisory Committee can offer valuable contributions to the treatment of patients with Barrett's oesophagus.

Academic Medical Centers↗

Autofluorescence endoscopy: feasibility of detection of GI neoplasms unapparent to white light endoscopy with an evolving technology.

BACKGROUND: Case studies are presented of fluorescence endoscopy in the upper and lower GI tract to illustrate the ability to detect early-stage lesions that were not observable with white light endoscopy or those in which the assessment of the stage or extension of the lesion were equivocal. METHODS: A new fluorescence imaging system was used in which blue light excites the naturally-occurring fluorescence of tissues (autofluorescence). The system produces real-time, false-color images that combine green and red fluorescence intensities. In general, abnormal lesions are seen to have an increase in the red-to-green fluorescence intensity compared with surrounding tissue. This system was evaluated in patients at 4 participating institutions, concurrently with standard white light endoscopy, with or without dye staining. RESULTS: Selected cases are presented in which fluorescence imaging identified specific lesions including focal high-grade dysplasia in Barrett's mucosa, signet ring carcinoma of the stomach, and flat adenoma in the colon. CONCLUSIONS: The capability of autofluorescence endoscopy to detect the presence and extent of occult malignant and premalignant GI lesions has been demonstrated. The future development and evaluation of this technology are discussed.

Adenocarcinoma↗

Red streaks in the oesophagus in patients with reflux disease: is there a histomorphological correlate?

BACKGROUND: The Los Angeles classification of reflux oesophagitis includes sharply demarcated areas of erythema without any associated slough within the definition of reflux-induced mucosal breaks, though there is uncertainty as to whether these "red streaks" actually represent such a mucosal lesion. This study evaluates the histopathology of these red streaks. METHODS: Forty patients with one or more red streaks on the tops of the mucosal folds in the distal oesophagus were included in a multinational, multicentre prospective study. All patients were referred for upper gastrointestinal endoscopy to investigate chronic heartburn and acid regurgitation. Biopsies were taken from the red streaks and from control biopsies from more normal appearing mucosa 1 cm lateral to the red streaks. A two-sided probability test using normal approximation assessed differences in the histological findings at the two biopsy locations. RESULTS: Compared to control biopsies, biopsies of red streaks had a significantly thicker basal cell layer (mean +/- s 41% +/- 32% versus 18% +/- 23% of mucosal thickness, P=0.001) and longer papillae (mean +/- s 71% +/- 19% versus 49% +/- 24% of mucosal thickness, P= 0.001). Of the red streak biopsies, 25% had either newly re-epithelized lesions or granulation tissue beneath squamous epithelium. Only 10% of the control biopsies had moderate or more marked regenerative changes (based on elongation of papillae and basal cell hyperplasia), compared to 65.1% of red streak biopsies. Of the biopsies from the red streak itself, 7% showed no abnormality and 27.9% only slight changes. In comparison, 25% of the biopsies from control biopsies showed no regenerative changes and 62.5% only slight change due to gastro-oesophageal reflux disease. CONCLUSION: The histomorphological counterpart to the endoscopically visible red streaks of the distal oesophagus is marked regenerative changes of the squamous epithelium and/or capillary rich granulation tissue beneath the squamous epithelium. Red streaks are validated as being indicative of acid/peptic mucosal injury, but they do not satisfy a strict definition of a mucosal break.

Biopsy↗

Palliation of patients with esophagogastric neoplasms by insertion of a covered expandable modified Gianturco-Z endoprosthesis: experiences in 153 patients.

BACKGROUND: We aimed to evaluate the short- and long-term outcomes of treatment by insertion of a covered expandable modified Gianturco-Z endoprosthesis (Song stent) in patients with esophagogastric malignancies. METHODS: Consecutive patients with esophagogastric malignancies in whom a Song stent was inserted were included. Data were retrieved retrospectively. Dysphagia before and after stent placement was scored on a 5-point scale. Early (less than 30 days) and late complications (more than 30 days) were scored. RESULTS: Analysis included 164 stents in 153 patients. Indications for stent placement were dysphagia and/or fistulas/perforations. The dysphagia score improved from a mean of 3.7 to 2.2 after stent placement (p < 0.0001). Fistulas/perforations sealed in 87% of cases. Early complications after stent placement occurred in 29.9% of cases. These included stent migration (4.3%), stent obstruction (6. 1%), aspiration pneumonia (4.9%), bleeding (4.3%), perforation (1. 8%), and pain (15.9%). Late complications occurred in 27.8% of cases. These included stent migration (2.6%), stent obstruction (9.6%), aspiration pneumonia (2.6%), bleeding (7.0%), perforation (0.9%), and pain (12.2%). The 30-day mortality was 26%. Death related to stent placement occurred in 3.3%. CONCLUSION: Insertion of a Song expandable endoprosthesis in patients with esophagogastric malignancies significantly improves dysphagia, is successful in sealing fistulas/perforations, and is associated with acceptable morbidity and mortality rates.

Aged↗