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Biomedical subjects

P D Siersema

Publications and source records attributed to P D Siersema.

At least 19 recordsLinked to original sources

Chemotherapy for metastatic carcinoma of the esophagus and gastro-esophageal junction.

BACKGROUND: More than 50% of patients with esophageal cancer have metastatic disease at presentation. The use of chemotherapy for this patient group is increasing with the intention of local and distant tumor control, improving quality of life and prolongation of survival. OBJECTIVES: To assess the effectiveness of a) chemotherapy versus best supportive care or b) different chemotherapy regimes against each other, in metastatic esophageal carcinoma. SEARCH STRATEGY: Searches were conducted on the Cochrane Central register of Controlled Trials--CENTRAL (which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register) on The Cochrane Library (Issue 1 2004) MEDLINE (1966 to February 2004), EMBASE (1980 to February 2004) and Cancerlit. Reference lists from trials selected by electronic searching were handsearched to identify further relevant trials. Published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were handsearched. The search was updated in February 2005 and February 2006. Members of the Cochrane UGPD Group, and experts in the field were contacted and asked to provide details of outstanding clinical trials and any relevant unpublished materials SELECTION CRITERIA: Randomized controlled trials comparing chemotherapy versus best supportive care, or different chemotherapy regimes against each other in patients with metastatic carcinoma of the esophagus or gastro-esophageal junction. DATA COLLECTION AND ANALYSIS: Two authors (MYVH/EJK) extracted data and assessed trial quality. Study authors were contacted to obtain subgroup results of patients with metastatic esophageal carcinoma. MAIN RESULTS: Only two RCTs with a total of 42 participants compared chemotherapy with best supportive care for metastatic esophageal cancer. No survival benefit was shown for chemotherapy treatment in these RCTs. Five RCTs with a total of 1242 participants compared different chemotherapy regimes. Due to variation in patient population and chemotherapy regimes, it was not possible to perform a formal pooled analysis. There was no consistent benefit of any specific chemotherapy regimen. AUTHORS' CONCLUSIONS: There is a need for well designed, adequately powered, phase III trials comparing chemotherapy versus best supportive care for patients with metastatic esophageal cancer. Chemotherapy agents with promising response rates and tolerable toxicity are cisplatin, 5-fluorouracil (5-FU), paclitaxel and antracyclins. Future trials comparing palliative treatment modalities should assess quality of life with validated quality of life measures.

Antineoplastic Combined Chemotherapy Protocols↗

[Gastrojejunostomy versus endoscopic stent placement as palliative treatment for a malignant constriction of the duodenum: the SUSTENT-study].

Gastric-outlet obstruction often results from inoperable distal stomach, periampullary (pancreatic or cholangio-), or duodenal carcinoma. Gastrojejunostomy and stent placement are standard palliative treatments. An advantage of gastrojejunostomy is the long-term efficacy; a disadvantage is the prolonged postoperative recovery time. The advantage of stent placement is the rapid ability to consume a soft diet; a disadvantage is that around 20% of the patients require re-intervention because of recurrent symptoms. A randomised multicentre study was started in January 2006 in the Netherlands in which gastrojejunostomy is compared with stent placement in the palliative treatment of malignant gastroduodenal obstruction: 'Surgery versus stent for malignant gastroduodenal obstruction', the SUSTENT-study. The primary-outcome measurement is survival adjusted for the time patients are not able to consume (soft) food. Other outcome measurements are medical effects (complications, re-interventions), quality of life, cost and cost-effectiveness. This study aims to provide individualised recommendations for effective palliative treatment of patients with malignant gastroduodenal obstruction.

Digestive System Neoplasms↗

The role of socio-economic status in the decision making on diagnosis and treatment of oesophageal cancer in The Netherlands.

In the United States (USA), a correlation has been demonstrated between socio-economic status (SES) of patients on the one hand, and tumour histology, stage of the disease and treatment modality of various cancer types on the other hand. It is unknown whether such correlations are also involved in patients with oesophageal cancer in The Netherlands. Between 1994 and 2003, 888 oesophageal cancer patients were included in a prospective database with findings on the diagnostic work-up and treatment of oesophageal cancer. Socio-economic status of patients was defined as the average net yearly income. Linear-by-linear association testing revealed that oesophageal adenocarcinoma was more frequently observed in patients with higher SES and squamous cell carcinoma in patients with lower SES (P=0.02). Multivariable logistic regression analysis showed no correlation between SES and staging procedures and preoperative TNM stage. The adjusted odds ratio (OR) for stent placement was 0.82 (95% CI 0.71-0.95), indicating that with an increase in SES by 1200 [euro], the likelihood that a stent was placed declined by 18%. Patients with a higher SES more frequently underwent resection or were treated with chemotherapy (OR: 1.15; 95% CI 1.01-1.32 and OR: 1.16; 95% CI 1.02-1.32, respectively). Socio-economic factors are involved in oesophageal cancer in The Netherlands, as patients with a higher SES are more likely to have an adenocarcinoma and patients with a lower SES a squamous cell carcinoma. Moreover, the correlations between SES and different treatment modalities suggest that both patient and doctor determinants contribute to the decision on the most optimal treatment modality in patients with oesophageal cancer.

Adenocarcinoma↗

[Guideline 'Diagnosis and treatment of oesophageal carcinoma'].

An evidence-based guideline for the diagnosis and treatment of oesophageal carcinoma was developed on the initiative of the Netherlands Society of Gastroenterohepatology in cooperation with the Dutch Institute for Healthcare Improvement (CBO) and the Dutch Association of Comprehensive Cancer Centres. If a patient with oesophageal carcinoma is eligible for treatment with curative intent, they should undergo thoracic and abdominal CT, ultrasound investigation of the supraclavicular region and endoscopic ultrasonography for staging purposes. Endoscopic therapy is the preferred treatment for high-grade dysplasia or early cancer in Barrett's oesophagus confined to the mucosa. Surgical resection is indicated if the tumour invades the submucosa. If resection of the oesophageal carcinoma is performed with curative intent, one should aim for radical resection. The type and extent of the resection depends on the location of the tumour. There is evidence that the mortality rate following surgery can be reduced by performing it in centres with ample experience with oesophageal cancer surgery. Preoperative chemotherapy and radiotherapy may improve survival in patients with oesophageal carcinoma. Palliative treatment for oesophageal carcinoma should be considered in cases of local invasion of surrounding organs, metastases, poor physical condition of the patient or recurrent disease after previous curative treatment. Psychosocial support is an important element in the follow-up of patients with oesophageal carcinoma.

Antineoplastic Agents↗

Persistence and adherence to proton pump inhibitors in daily clinical practice.

BACKGROUND: Proton pump inhibitors are widely used, but little is known about the usage pattern in different indications. AIM: To analyse proton pump inhibitor usage patterns in the general population. METHODS: A cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis. RESULTS: One-year persistence was 31% in patients using proton pump inhibitors for gastro-oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non-reflux dyspepsia or Helicobacter pylori-associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent. CONCLUSIONS: A substantial proportion of patients with indications not requiring long-term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on-demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus.

Adult↗

Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study.

This study was performed to assess the efficacy and safety of preoperative chemoradiation consisting of carboplatin and paclitaxel and concurrent radiotherapy for patients with resectable (T2-3N0-1M0) oesophageal cancer. Treatment consisted of paclitaxel 50 mg m(-2) and carboplatin AUC=2 on days 1, 8, 15, 22 and 29 and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by oesophagectomy. All 54 entered patients completed the chemoradiation without delay or dose-reduction. Grade 3-4 toxicities were: neutropaenia 15%, thrombocytopaenia 2%, and oesophagitis 7.5%. After completion of the chemoradiotherapy 63% had a major endoscopical response. Fifty-two patients (96%) underwent a resection. The postoperative mortality rate was 7.7%. All patients had an R0-resection. The pathological complete response rate was 25%, and an additional 36.5% had less than 10% vital residual tumour cells. At a median follow-up of 23.2 months, the median survival time has not yet been reached. The probability of disease-free survival after 30 months was 60%. In conclusion, weekly neoadjuvant paclitaxel and carboplatin with concurrent radiotherapy is a very tolerable regimen and can be given on an outpatient basis. It achieves considerable down staging and a subsequent 100% radical resection rate in this series. A phase III trial with this regimen is now ongoing.

Adenocarcinoma↗

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↗

Follow-up after surgical treatment for cancer of the gastrointestinal tract.

BACKGROUND: Presently, no evidence-based guidelines for the follow-up of patients after surgery for gastrointestinal cancer are available. As a consequence, follow-up strategies may differ between hospitals depending on preference of physicians. We investigated which follow-up procedures are currently employed after surgery for gastrointestinal cancer in the Netherlands. METHOD: A questionnaire was sent to all surgical departments in the Netherlands. The questionnaire focused on frequency of follow-up visits and diagnostic procedures after surgical treatment for oesophageal, gastric, pancreatic and colorectal cancer and psychosocial issues during follow-up. RESULTS: The response rate was 90% (83/92). In the majority of hospitals, surgeons treated patients with colorectal (100%) and gastric (96%) cancer in their own centre, whereas patients with pancreatic (64%) and oesophageal (61%) cancer were more often referred to a tertiary centre. For all patients treated for gastrointestinal cancer, three to four follow-up visits were made in the first year, followed by at least two annual visits thereafter. After colorectal surgery, blood tests (78%), colonoscopy (75%) and abdominal ultrasound (57%) were frequently performed. In other gastrointestinal malignancies, procedures were in most cases only performed if symptoms occurred. In almost three-quarters of patients, psychosocial problems were observed, which were dealt with by surgeons in two-thirds of patients. The majority of patients treated for gastrointestinal cancer were pre- and postoperatively discussed in a multidisciplinary setting. Oncologists, gastroenterologists and dieticians were the most frequently consulted specialists after surgery for gastrointestinal cancer. CONCLUSION: Patients frequently visit the outpatient clinic after surgery for gastrointestinal cancer in the Netherlands. Whereas follow-up after colorectal cancer surgery focuses on finding recurrent disease and metachronous lesions in the colorectum, this is less clear after oesophageal, gastric and pancreatic cancer surgery. Further studies are needed to establish what is the most effective follow-up protocol after different types of gastrointestinal cancer surgery.

Blood Cell Count↗

The burden of upper gastrointestinal endoscopy in patients with Barrett's esophagus.

BACKGROUND AND STUDY AIMS: Patients with Barrett's esophagus are recommended to undergo regular surveillance with upper gastrointestinal endoscopy, an invasive procedure that may cause anxiety, pain, and discomfort. We assessed to what extent patients perceived this procedure as burdensome. PATIENTS AND METHODS: A total of 192 patients with Barrett's esophagus were asked to fill out questionnaires at 1 week and immediately before endoscopy, and at 1 week and 1 month afterwards. Four variables were assessed: (i) pain and discomfort experienced during endoscopy; (ii) symptoms; (iii) psychological burden, i. e., anxiety, depression and distress levels (Hospital Anxiety and Depression scale, Impact of Event Scale); and (iv) perceived risk of developing adenocarcinoma. RESULTS: At least one questionnaire was returned by 180 patients (94 %), 151 completed all four (79 %). Of all patients, only 14 % experienced the endoscopy as painful. However, 59 % reported it to be burdensome. Apart from an increase in throat ache (47 % after endoscopy versus 12 % before), the procedure did not cause physical symptoms. Patients' anxiety, depression, and distress levels were significantly increased in the week before endoscopy compared with the week after. Patients perceiving their risk of developing adenocarcinoma as high reported higher levels of psychological distress and that the procedure was a greater burden. CONCLUSIONS: Upper gastrointestinal endoscopy is burdensome for many patients with Barrett's esophagus and causes moderate distress. Perception of a high risk of adenocarcinoma may increase distress and the burden experienced from the procedure. The benefits of endoscopic surveillance for patients with Barrett's esophagus should be weighed against its drawbacks, including the short-term burden for patients.

Adenocarcinoma↗

Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar epithelium without goblet cells?

BACKGROUND: Intestinal metaplasia (Barrett's oesophagus), but not cardiac-type mucosa in columnar-lined oesophagus, is regarded as premalignant. As intestinal metaplasia and cardiac-type mucosa are endoscopically indiscernible, it is difficult to take targeted samples from columnar-lined oesophagus with consequently a risk of having undetected intestinal metaplasia. AIM: To investigate whether the intestinal markers CDX2, MUC2 and villin can predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus. Methods Presence of intestinal metaplasia or cardiac-type mucosa was identified in 122 biopsy sets of columnar-lined oesophagus from 61 patients, collected at two subsequent follow-up upper endoscopies. CDX2, MUC2 and villin expression were determined by immunohistochemistry. RESULTS: All intestinal metaplasia samples (55) were positive for CDX2 and MUC2 and 32 of 55 for villin. CDX2 expression was detected in 23 of 67 (34%) samples with only cardiac-type mucosa. Detection of CDX2 in cardiac-type mucosa increased the likelihood of finding intestinal metaplasia in another biopsy set of columnar-lined oesophagus (odds ratio 3.5, 95% CI = 1.2-10, P = 0.02). MUC2 was positive in 13 of 23 (57%) of CDX2-positive cardiac-type mucosa samples, whereas villin was detected in seven of 23 (30%). CONCLUSIONS: CDX2 expression in cardiac-type mucosa might be able to predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus, and thus may be a putative marker for the presence of intestinal metaplasia in the absence of goblet cells.

Adult↗

Experiences and expectations of patients after oesophageal cancer surgery: an explorative study.

We investigated which problems patients experience after resection for oesophageal cancer and what care they expect, in order to devise a better-tailored follow-up policy. Thirty patients, all within 1 year after surgery, filled in a one-time questionnaire on experienced physical, psychological and social problems and on expected care for these problems. Additionally, a semi-structured interview was performed. Frequencies of experienced problems and expected care over time were analysed. The majority of patients experienced physical problems such as 'early satiety' (97%) and 'fatigue' (84%) after oesophagectomy. In addition, patients often felt depressed (64%), were afraid of metastases (80%) and death (47%). Over time, the frequency of problems such as 'fatigue' (P = 0.035) and 'being dependent' (P = 0.012) decreased. Patients particularly expected professional care for physical issues related to their disease, whereas they often managed psychosocial problems in their own social network. Patients indicated that nurses' involvement during follow-up might improve their possibility to satisfactorily deal with problems. Patients frequently experience physical problems after oesophagectomy, and professional care is expected for these issues. Psychosocial problems are also present, but care is less commonly expected. Nurses' involvement during follow-up could be a way to optimize patients' management after oesophageal cancer surgery.

Antineoplastic Combined Chemotherapy Protocols↗

[Palliative treatment in patients with oesophagus carcinoma].

More than 50% of patients with oesophageal carcinoma will undergo palliative treatment because of distant metastases or local tumour ingrowth into surrounding organs. The majority of these patients have symptoms ofdysphagia. If metastases from oesophageal carcinoma are present, the most commonly used treatment modalities for dysphagia in The Netherlands are placement of a self-expanding stent or intraluminal radiotherapy (brachytherapy). If the life expectancy of patients is longer than 3 months, brachytherapy is sometimes combined with external radiotherapy. If patients with metastases are in a good condition, chemotherapy may be considered. If there is local tumour ingrowth but no metastases, chemotherapy in combination with radiation therapy (chemoradiation) is an option. These treatments should preferably make up part of well-designed studies. Quality of life is an important endpoint to consider in the palliative treatment of patients with oesophageal cancer. Well-established standardized and validated questionnaires are available for this purpose.

Brachytherapy↗

[Palliative treatment of esophageal cancer with dysphagia: more favourable outcome from single-dose internal brachytherapy than from the placement of a self-expanding stent; a multicenter randomised study].

OBJECTIVE: To compare the results of single-dose internal irradiation (brachytherapy) and self-expanding metal stent placement in the palliation of oesophageal obstruction due to cancer of the oesophagus. DESIGN: Randomised trial. METHOD: In the period from December 1999-Jun 2002, 209 patients with dysphagia due to inoperable carcinoma of the oesophagus were randomised to placement of an Ultraflex stent (n = 108) or single-dose (12 Gy) brachytherapy (n = 101). Primary outcome was relief of dysphagia; secondary outcomes were complications, persistent or recurrent dysphagia, health-related quality of life, and costs. Patients were followed up by monthly home visits from a specialised nurse. RESULTS: Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement resulted in more complications than did brachytherapy (36/108 (33%) versus 21/101 (21%); p = 0.02), due mainly to an increased incidence of late haemorrhage in the stent group (14 versus 5; p = 0.05). The groups did not differ with regard to the incidence of persistent or recurrent dysphagia or median survival (p > 0.20). In the long term, quality-of-life scores were higher in the brachytherapy group. Total medical costs were also similar for both treatments: Euro 8,215 for stent placement and Euro 8,135 for brachytherapy. CONCLUSION: Brachytherapy provided better long-term relief of dysphagia than did stent placement and also produced fewer complications. Brachytherapy is therefore recommended as the preferred treatment for the palliation of dysphagia due to oesophageal cancer.

Aged↗

Increasing incidence of Barrett's oesophagus in the general population.

BACKGROUND: Barrett's oesophagus (BO) predisposes to oesophageal adenocarcinoma. Epidemiological data suggest that the incidence of BO is rising but it is unclear whether this reflects a true rise in incidence of BO or an increase in detection secondary to more upper gastrointestinal endoscopies performed. This study aimed to examine the changes in BO incidence relative to the number of upper gastrointestinal endoscopies performed in the general population. METHODS: We conducted a cohort study using the Integrated Primary Care Information database. This general practice research database contains the complete and longitudinal electronic medical records of more than 500,000 persons. RESULTS: In total, 260 incident cases of BO were identified during the study period. The incidence of BO increased from 14.3/100,000 person years in 1997 (95% confidence interval (CI) 8.6-22.4) to 23.1/100,000 person years (95% CI 17.2-30.6) in 2002 (r2 = 0.87). The number of upper gastrointestinal endoscopies decreased from 7.2/1000 person years (95% CI 6.7-7.7) to 5.7/1000 person years (95% CI 5.4-6.1) over the same time period. This resulted in an overall increase in detected BO per 1000 endoscopies from 19.8 (95% CI 12.0-31.0) in 1997 to 40.5 (95% CI 30.0-53.5) in 2002 (r2 = 0.93). The incidence of adenocarcinoma increased from 1.7/100,000 person years (95% CI 0.3-5.4) in 1997 to 6.0/100,000 person years (95% CI 3.3-10.2) in 2002 (r2 = 0.87). CONCLUSION: The incidence of diagnosed BO is increasing, independent of the number of upper gastrointestinal endoscopies that are being performed. This increase in BO incidence will likely result in a further increase in the incidence of oesophageal adenocarcinomas in the near future.

Adenocarcinoma↗

Cost study of metal stent placement vs single-dose brachytherapy in the palliative treatment of oesophageal cancer.

Self-expanding metal stent placement and single-dose brachytherapy are commonly used for the palliation of oesophageal obstruction due to inoperable oesophagogastric cancer. We randomised 209 patients to the placement of an Ultraflex stent (n=108) or single-dose brachytherapy (12 Gy, n=101). Cost comparisons included comprehensive data of hospital costs, diagnostic interventions and extramural care. We acquired detailed information on health care consumption from a case record form and from monthly home visits by a specialised nurse. The initial costs of stent placement were higher than the costs of brachytherapy (1500 euro vs 570 euro; P<0.001). Total medical costs were, however, similar (stent 11 195 euro vs brachytherapy 10 078 euro, P>0.20). Total hospital stay during follow-up was 11.5 days after stent placement vs 12.4 days after brachytherapy, which was responsible for the high intramural costs in both treatment groups (stent 6512 euro vs brachytherapy 7982 euro, P>0.20). Costs for medical procedures during follow-up were higher after stent placement (stent 249 euro vs brachytherapy 168 euro, P=0.002), while the costs of extramural care were similar (1278 euro vs 1046 euro, P>0.20). In conclusion, there are only small differences between the total medical costs of both palliative treatment modalities, despite the fact that the initial costs of stent placement are much higher than those of brachytherapy. Therefore, cost considerations should not play an important role in decision making on the appropriate palliative treatment strategy for patients with malignant dysphagia.

Aged↗