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Biomedical subjects

Peter D Siersema

Publications and source records attributed to Peter D Siersema.

At least 37 records · Page 2Linked to original sources

Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction.

Adenocarcinoma of the esophagus, or GEJ, has a poor prognosis. Early lesions [i.e. high grade dysplasia (HGD) or T1-carcinoma] are potentially curable. Local endoscopic therapies are promising treatment options for superficial lesions; however, for deeper lesions, surgical resection is considered to be the treatment of choice. To contribute to therapeutic decision-making, we retrospectively analysed the outcome of transhiatal esophagectomy in 120 patients with pathologically proven HGD (n=13) or T1-adenocarcinoma (n=107) of the distal esophagus or gastro-esophageal junction (GEJ). Tumors were subdivided into six different depths of invasion ('T1-mucosal' m1-m3, 'T1-submucosal' sm1-sm3), and the frequency of lymphatic dissemination and time to locoregional and/or distant recurrence were analysed. Only one of the 79 T1m1-3/sm1 tumors (1%) showed lymph node metastases as compared with 18 out of 41 T1sm2-3 tumors (44%). There was a significant difference in recurrence-free period between T1m1-m3/sm1 versus T1sm2-sm3 tumor patients (P log rank <0.0001), with 5-year recurrence-free percentages of 97% and 57%, respectively. In multivariate analysis including age, gender, tumor differentiation grade, N-stage and depth of invasion, only N-stage was an independent prognostic factor for recurrence-free period (hazard rate=5.9, 95% CI 1.7-20.7). However, if N-stage was excluded from analysis, only depth of invasion (T1sm2-3 versus T1m1-m3/sm1) was an independent prognostic factor for recurrence-free period (hazard rate=7.5, 95% CI 2.0-27.7). These data indicate that T1m1-m3/sm1 adenocarcinomas of esophagus or GEJ show a very low risk of lymphatic dissemination and are therefore eligible for local endoscopic therapy. After transhiatal surgical resection, almost half of the patients with T1sm2-sm3 lesions develop recurrent disease within 5 years, and therefore need additional therapy to improve survival.

Adenocarcinoma↗

Molecular evaluation of ablative therapy of Barrett's oesophagus.

Barrett's oesophagus is a major risk factor for developing oesophageal adenocarcinoma. Ablation by argon plasma coagulation (APC) and photodynamic therapy (PDT) is currently under investigation for the removal of metaplastic and dysplastic Barrett's oesophagus. This study examined the effect of ablative therapy on Barrett's oesophagus at cell-cycle and genetic levels. The premalignant potential of residual or recurring Barrett's oesophagus was assessed by p53 immunohistochemistry, Ki67-related proliferative capacity, and DNA ploidy status (ie an abnormal chromosome 1 number) as measured by interphase in situ hybridization. Twenty-nine patients with Barrett's oesophagus (23 male and 6 female, mean age 58 years, mean length of Barrett's oesophagus 4 cm) were treated with APC or PDT. Intestinal metaplasia without dysplasia was present in 16 patients, low-grade dysplasia in five, and high-grade dysplasia in eight patients. Biopsy samples were obtained at regular intervals (mean follow-up 20 months, range 6-36 months). One month after the first ablation, Barrett's oesophagus was no longer identified, either endoscopically or histologically, in nine patients (32%). At this time point, significant down-grading was achieved for abnormal chromosome 1 numbers (p = 0.020) and Ki67-defined proliferation (p = 0.002). Patients with residual Barrett's oesophagus were additionally treated with APC, resulting in the elimination of Barrett's oesophagus in 76% of all patients. However, at the last follow-up endoscopy, metaplasia without dysplasia was still present in five patients, and low- and high-grade dysplasia were each present in one patient. An abnormal chromosome 1 number and p53 protein overexpression were detected only in the high-grade dysplastic lesion, but increased proliferation was still present in the majority of these persisting cases. Although endoscopic removal of Barrett's oesophagus by ablative therapies is possible in the majority of patients, histologically complete elimination cannot be achieved in all cases. Persistent Barrett's oesophagus may still harbour molecular aberrations and must therefore be considered still to be at risk of progression to adenocarcinoma.

Adult↗

Barrett's oesophagus is characterized by a predominantly humoral inflammatory response.

Barrett's oesophagus (BO) is thought to be an intermediate step in the progression from reflux oesophagitis (RO) to oesophageal adenocarcinoma. Premalignant conditions that develop in the presence of chronic inflammation are often associated with the development of a more pronounced humoral immune response during progression of the disease. The aim of this study was to determine whether BO is also associated with a more pronounced humoral immune response when compared to RO. Immunohistochemical studies were performed to quantify the mean numbers of Th2 effector cells (plasma cells and mast cells) and Th1 effector cells (macrophages and CD8(+) T cells) to detect the antibody classes produced by plasma cells (IgA, IgG, IgM or IgE) and to determine the presence of isolated lymph follicles [segregated B and T cell areas, follicular dendritic cells (CD23) and expression of CXCL13] in 124 oesophageal biopsies from 20 patients with BO and 20 patients with RO. The proportion of Th2 effector cells was higher in BO than in RO, mainly due to higher numbers of plasma cells and mast cells in BO (p < 0.001). Most plasma cells in BO and RO expressed IgG, but several IgE(+) plasma cells were detected in BO: these were rare in RO. In line with this, isolated lymph follicles were observed in 4/20 (20%) patients with BO, but not in RO. We therefore conclude that the inflammatory response is skewed towards a more pronounced humoral immune response when RO progresses to BO. It may be that this shift, which is similar to that found in other chronic inflammatory conditions, contributes to an increased cancer risk in BO.

Aged↗

Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer: a prognostic model to guide treatment selection.

BACKGROUND: Brachytherapy was found to be preferable to metal stent placement for the palliation of dysphagia because of inoperable esophageal cancer in the randomized SIREC trial. The benefit of brachytherapy, however, only occurred after a relatively long survival. The objective is to develop a model that distinguishes patients with a poor prognosis from those with a relatively good prognosis. METHODS: Survival was analyzed with Cox regression analysis. Dysphagia-adjusted survival (alive with no or mild dysphagia) was studied with Kaplan-Meier analysis. Patient data is from the multicenter, randomized, controlled trial (SIREC, n = 209) and a consecutive series (n = 396). Patients received a stent or single-dose brachytherapy. RESULTS: Significant prognostic factors for survival included tumor length, World Health Organization performance score, and the presence of metastases (multivariable p < 0.001). A simple score, which also included age and gender, could satisfactorily separate patients with a poor, intermediate, and relatively good prognosis within the SIREC trial. For the poor prognosis group, the difference in dysphagia-adjusted survival was 23 days in favor of stent placement compared with brachytherapy (77 vs. 54 days, p = 0.16). For the other prognostic groups, brachytherapy resulted in a better dysphagia-adjusted survival. CONCLUSIONS: A simple prognostic score may help to identify patients with a poor prognosis in whom stent placement is at least equivalent to brachytherapy. If further validated, this score can provide an evidence-based tool for the selection of palliative treatment in esophageal cancer patients.

Aged↗

Reduced medication dependency and improved symptoms and quality of life 12 months after enteryx implantation for gastroesophageal reflux.

BACKGROUND: The need is well recognized for additional data on endoluminal therapies for gastroesophageal reflux disease (GERD). This prospective multicenter clinical trial was designed to assess safety and effectiveness of Enteryx, a nonresorbable copolymer implanted into the lower esophagus, in reducing usage of proton pump inhibitors (PPIs) and improving reflux symptoms and quality of life. METHODS: Enteryx implantation was performed under fluoroscopic visualization without general anesthesia in 93 patients with symptomatic GERD responsive to and relapsing upon cessation of PPI therapy. Subjective and objective data were collected up to 12 months postprocedure. The criterion for treatment success was reduction in PPI dosage of > or =50%. RESULTS: At 12 months, treatment success was attained in 86% (confidence interval, 77%-93%) of 74 evaluable patients and elimination of PPI therapy in 65% (confidence interval, 53%-76%). The treatment success rate by intent-to-treat analysis was 69% (confidence interval, 58%-78%). Reflux-related heartburn (P < 0.0001), regurgitation symptoms (P = 0.0005), and physical (P < 0.0001) and mental quality of life (P = 0.0012) scores improved. The most frequent complications were chest pain (77%), dysphagia/odynophagia (27%), and sensation of fever (26%). CONCLUSIONS: Enteryx implantation provides an effective and safe alternative for management of gastroesophageal reflux, reducing medication dependency and symptoms and enhancing quality of life.

Female↗

Endoscopic therapeutic esophageal interventions: what is new? What needs further study? What can we forget?

PURPOSE OF THIS REVIEW: Endoscopic esophageal interventions form an important part of gastrointestinal endoscopy. This article reviews the most notable results of esophageal endoscopy and interventions published in 2004. RECENT FINDINGS: Both argon plasma coagulation and photodynamic therapy were shown to have high success rates in removing Barrett's epithelium. After ablative treatment, residual Barrett's esophagus still poses an increased esophageal cancer risk and is a concern. Endoscopic resection is now an accepted alternative to surgical resection of early-stage squamous cell and adenocarcinoma of the esophagus. Four studies convincingly demonstrated that covered plastic stents could be used in the initial therapy of patients with refractory benign esophageal strictures, and anastomotic leaks after esophageal surgery. Evidence was presented that intraluminal radiotherapy (brachytherapy) is a valuable alternative to stent placement in patients with malignant dysphagia. It has become clear that injections with botulinum toxin at the gastroesophageal junction in patients with achalasia are often only temporarily effective. It was shown that endoluminal gastroplication produced good symptomatic results; however, data on the reduction of esophageal acid exposure were less impressive. Finally, the first results of endoscopic implantation of expandable antireflux prostheses (Gatekeeper Reflux Repair System, Medtronic Europe, Tolochenaz, Switzerland) in the distal esophageal submucosa were reported. SUMMARY: In 2004, new data on available esophageal therapeutic techniques became available. In addition, new information on an old established technique (brachytherapy for malignant dysphagia) and a new device (Gatekeeper system for the prevention of reflux) were presented.

Dilatation↗

Quality of life after palliative treatment for oesophageal carcinoma -- a prospective comparison between stent placement and single dose brachytherapy.

Metal stent placement and single dose brachytherapy are commonly used treatment modalities for the palliation of inoperable oesophageal carcinoma. We investigated generic and disease-specific health-related quality of life (HRQoL) after these palliative treatments. Patients with dysphagia from inoperable oesophageal carcinoma were randomised to placement of a covered Ultraflex stent (n = 108) or single dose (12 Gy) brachytherapy (n = 101). We obtained longitudinal data on disease-specific (dysphagia score, European Organisation for Research and Treatment of Cancer (EORTC) OES-23, visual analogue pain scale) and generic (EORTC Quality of Life-Core 30 Questionnaire (QLQ-C30), Euroqol (EQ)-5D) HRQoL at monthly home visits by a specially-trained research nurse. We compared HRQoL between the two treatments and analysed changes in HRQoL during follow-up. Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. For generic HRQoL, there was an overall significant difference in favour of brachytherapy on four out of five functional scales of the EORTC QLQ-C30 (role, emotional, cognitive and social) (P < 0.05). Generic HRQoL deteriorated over time on all functional scales of the EORTC QLQ C-30 and EQ-5D, in particular physical and role functioning (on average -23 and -24 on a 100 points scale during 0.5 years of follow-up). This decline was more pronounced in the stent group. Major improvements were seen on the dysphagia and eating scales of the EORTC OES-23, in contrast to other scales of this disease-specific measure, which remained almost stable during follow-up. Reported levels of chest or abdominal pain remained stable during follow-up in both treatment groups, general pain levels increased to a minor extent. The effects of single dose brachytherapy on HRQoL compared favourably to those of stent placement for the palliation of oesophageal cancer. Future studies on palliative care for oesophageal cancer should at least include generic HRQoL scales, since these were more responsive in measuring patients' functioning and well-being during follow-up than disease-specific HRQoL scales.

Aged↗

Ingestion of acid and alkaline agents: outcome and prognostic value of early upper endoscopy.

BACKGROUND: Ingestion of caustic substances often leads to severe morbidity and, frequently, death. This study compared complications and survival for patients who ingested an acidic substance, mainly glacial acetic acid, or an alkaline agent. METHODS: Records for 179 patients hospitalized for ingestion of a caustic agent (85 acid [75 glacial acetic acid], 94 alkali) were reviewed. Mucosal injury, systemic and GI complications, and survival were scored. RESULTS: Outcome was less favorable for patients who ingested acid compared with those who ingested alkali with respect to mucosal injury (median: grade 2 vs. grade 1; p=0.013), hospital stay (mean: 9.9 vs. 7.2 days; p=0.01), admittance to the intensive care unit (44% vs. 22%; p=0.002), systemic complications (24% vs. 3%; p < 0.001), perforation (6% vs. 0%; p=0.017), and mortality (14% vs. 2%; p=0.003). There was no difference in the development of strictures (acid, 15% vs. alkali, 17%). The grade of mucosal injury at endoscopy was the strongest predictive factor for the occurrence of systemic and GI complications and mortality (relative risk 9: 95% CI[3, 30]). Ten of 29 (34%) patients with strictures were treated by endoscopic dilation alone, whereas the others primarily (n=7) or secondarily (n=11) underwent surgery. One patient with an esophageal stricture died from systemic complications. CONCLUSIONS: Acid ingestion, particularly glacial acetic acid, is associated with a higher frequency of complications and mortality rate than alkali ingestion. Early endoscopy probably is safe and provides important prognostic information. Endoscopic treatment of caustic-induced strictures is only moderately successful.

Accidents↗

Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial.

BACKGROUND: Self-expandable metal stents deployed across the gastroesophageal junction predispose to gastroesophageal reflux. The efficacy of a stent with an antireflux mechanism in preventing gastroesophageal reflux was assessed. METHODS: Thirty patients with carcinoma of the distal esophagus or of the gastric cardia were randomized to receive either a stent with a windsock-type antireflux valve (FerX-Ella) (n = 15) or a standard open stent (n = 15) of the same design minus the valve. Gastroesophageal reflux was assessed by using standardized questionnaires and by 24-hour pH monitoring 14 days after treatment. RESULTS: Technical problems occurred during stent placement in 3 patients: migration (n = 2) and a problem with the introducing system (n = 1). Dysphagia improved from a median score of 3 (liquids only) to 1 (eat some solid food) in the antireflux group and from 3 to 0 (solid foods) in the open stent group ( p > 0.20). Reflux symptoms were reported by 3/12 patients (25%) with an antireflux stent and by 2/14 (14%) with an open stent. In 11 patients, 24-hour pH monitoring was obtained, and increased esophageal acid exposure (normal: <4%) was present with both types of stent: median 24-hour reflux time (9 patients) with the antireflux stent was 23% vs. 10% in (2 patients) with the open stent ( p = NS). Major complications occurred in 3 patients (20%) in each group and included bleeding (n = 3), severe pain (n = 2), and aspiration pneumonia (n = 1). The main cause of recurrent dysphagia was stent migration, which occurred in 7 of the 30 patients (23%). CONCLUSIONS: The FerX-Ella antireflux stent provided relief of dysphagia caused by malignancy of the distal esophagus and gastric cardia. However, the antireflux valve failed to prevent gastroesophageal reflux.

Aged↗

Endoscopic therapeutic esophageal interventions: something old, something new, something to be established.

PURPOSE OF REVIEW: Endoscopic esophageal interventions are an exciting topic because indications for the use of both the available devices and the new devices continue to evolve. This article reviews the most notable developments and the results of endoscopic esophageal therapeutic interventions published in 2003. RECENT FINDINGS: In 2003, three follow-up series on photodynamic therapy were published. Photodynamic therapy was shown to improve dysphagia from esophageal cancer, but comparative studies with other techniques are needed. Photodynamic therapy was also effective in removing Barrett epithelium. Of concern is that patients with residual Barrett esophagus after ablative treatment are still at an increased risk for esophageal cancer. Endoscopic mucosal resection has become an accepted alternative for surgical resection of early-stage esophageal cancer, with increasing evidence that lesions larger than 20 mm can be safely removed by this technique. Completely covered plastic self-expanding stents have been demonstrated to reduce recurrent dysphagia by the ingrowth or overgrowth of nonmalignant tissue. A new indication for self-expanding metal stents is the treatment of traumatic nonmalignant perforations of the esophagus. Stents are also increasingly used for strictures refractory to repeated dilations and as an alternative to pneumatic dilation in achalasia. Bleeding esophageal varices can safely be treated with vasoactive drugs, which is good news for endoscopists who value a good night's rest. Various follow-up studies of endoscopic antireflux procedures were published that suggested good symptomatic results. However, with respect to the reduction of acid exposure to the esophagus, these data were less impressive. SUMMARY: In 2003, much additional data about current techniques became available. In addition, new indications for existing devices were developed. Finally, for some techniques more information will be needed before their exact role can be established.

Journal Article↗

Prior radiation and/or chemotherapy has no effect on the outcome of metal stent placement for oesophagogastric carcinoma.

OBJECTIVE: It is still unclear whether prior radiation and/or chemotherapy (RTCT) increases the risk of complications after the placement of self-expanding metal stents in patients with inoperable oesophagogastric carcinoma. We evaluated the influence of prior RTCT on the outcome of stent placement in a large group of patients. METHODS: From October 1994 to December 2000, 200 patients underwent placement of self-expanding metal stents for malignant dysphagia, and were followed prospectively. Forty-nine of these patients had received prior RTCT (chemotherapy n = 35, radiation therapy n = 8, or both n = 6). RESULTS: At 4 weeks after stenting, the dysphagia score had improved similarly in patients with or without prior RTCT, from a median of 3 to 0 (P < 0.001). The occurrence of major complications (bleeding, perforation, fistula formation, fever and severe pain) was not different between patients with or without prior RTCT (29% vs 21%; relative risk (RR) = 1.15 (95% CI 0.54-2.46; P = 0.72)), as was the occurrence of recurrent dysphagia due to tumour overgrowth, stent migration, or impaction of a food bolus (35% vs 27%; RR = 1.49 (95% CI 0.71-3.13; P = 0.29)). Median survival of both patient groups after stent placement was similar (110 vs 93 days; RR = 0.90 (95% CI 0.60-1.34; P = 0.60) for prior RTCT versus no prior treatment). Only minor complications (mainly mild retrosternal pain) occurred more frequently in patients with prior RTCT (41% vs 15%; RR = 2.12 (95% CI 1.06-4.25; P = 0.035)). CONCLUSIONS: Both the incidence of life-threatening complications and survival after placement of self-expanding metal stents for oesophagogastric carcinoma are not affected by prior RTCT, but retrosternal pain occurs more frequently in patients who had previously undergone RTCT.

Aged↗

CT and MR colonography: scanning techniques, postprocessing, and emphasis on polyp detection.

In the last decade, computed tomographic (CT) and magnetic resonance (MR) colonography, two new cross-sectional techniques for imaging of the colon, emerged. Both techniques show promising initial results in the detection of polyps equal to or greater than 1 cm in diameter in symptomatic patients. Imaging protocols are still mostly under development and prone to change. Both CT and MR colonography generate a large number of source images, which have to be read carefully for filling defects and, if intravenous contrast material is used, enhancing lesions. An important postprocessing technique is multiplanar reformatting, which allows the viewer to see potential lesions in an orientation other than that of the source images. Virtual endoscopy, a volume rendering technique that generates images from within the colon lumen, is used for problem solving. CT and MR colonography have potential advantages over colonoscopy and double-contrast barium enema examination: multiplanar capabilities, detection of enhancing lesions that make the distinction between fecal residue and true lesion possible, and ante- and retrograde virtual colonoscopy. Currently, a number of studies suggest that patients have a preference for CT colonography over colonoscopy. Patients consider bowel cleansing the most uncomfortable part of any colon examination; hence, from the acceptance point of view, fecal tagging techniques are promising. Before CT and MR colonography can be implemented in daily practice, they must show approximately the same accuracy as colonoscopy for polyp detection in both symptomatic and screening patients.

Adenoma↗

High dose rate brachytherapy for the palliation of malignant dysphagia.

BACKGROUND AND PURPOSE: High dose rate (HDR) brachytherapy is a commonly used palliative treatment for esophageal carcinoma. We evaluated the outcome of HDR brachytherapy in patients with malignant dysphagia. MATERIAL AND METHODS: A retrospective analysis over a 10-year period was performed of 149 patients treated with HDR brachytherapy, administered in one or two sessions, at a median dose of 15Gy. Patients were evaluated for functional outcome, complications, recurrent dysphagia, and survival. RESULTS: At 6 weeks after HDR brachytherapy, dysphagia scores had improved from a median of 3 to 2 (n=104; P<0.001), however, dysphagia had not improved in 51 (49%) patients. Procedure-related complications occurred in seven (5%) patients. Late complications, including fistula formation or bleeding, occurred in 11 (7%) patients. Twelve (8%) patients experienced minor retrosternal pain. Median survival of the patients was 160 days with a 1-year survival rate of 15%. Procedure-related mortality was 2%. At follow-up, 55 (37%) patients experienced recurrent dysphagia. In 34 (23%) patients a metal stent was placed to relieve persistent or recurrent dysphagia. CONCLUSION: HDR brachytherapy is a moderately effective treatment for the palliation of malignant dysphagia. The incidence of early major complications is low, however, persistent and recurrent dysphagia occur frequently, and require often additional treatment.

Adenocarcinoma↗

Use of large-diameter metallic stents to seal traumatic nonmalignant perforations of the esophagus.

BACKGROUND: Surgery for traumatic, non-malignant perforation of the esophagus in patients presenting more than 24 hours after its occurrence carries a high morbidity and mortality. Covered metallic stents have been used to effectively seal perforations in individual patients with Boerhaave's syndrome. METHODS: Eleven consecutive patients presented with esophageal perforation that was caused by Boerhaave's syndrome (n = 5), resection of an epiphrenic diverticulum (n = 2), rigid esophagoscopy (n = 2), extended gastric resection (n = 1), or pneumatic dilation for achalasia (n = 1). A large diameter Flamingo Wallstent (proximal/distal diameters, 30/20 mm) (7 patients) or a large diameter Ultraflex stent (proximal/distal diameters, 28/23 mm) (4 patients) was placed. Pleural cavities were drained with thoracostomy drains, and antibiotics were administered. RESULTS: The median time from perforation to stent insertion was 60 hours (range, 24 hours to 28 days). The perforation was totally sealed in 10 of 11 patients. Two patients underwent esophageal resection because of incomplete sealing of the perforation or incomplete drainage of the pleural cavity and mediastinum. The other 9 patients recovered uneventfully and resumed a normal diet within 7 to 18 days. In 7 patients, the stents were retrieved endoscopically after a median of 7 weeks (range, 6 to 14 weeks), whereas two patients refused to have the stent retrieved (in one, the stent migrated into the stomach; the other patient died 6 months after stent placement from an unrelated cause). CONCLUSIONS: Traumatic perforation of the esophagus can be treated successfully with large diameter metallic stents, together with adequate drainage of the thoracic cavity.

Adult↗