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H W Tilanus

Publications and source records attributed to H W Tilanus.

At least 19 recordsLinked to original sources

Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis.

The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E-cadherin and alpha- and beta-catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico-pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E-cadherin, alpha-catenin, and beta-catenin was found in 74, 60, and 72 per cent, respectively. Expression of E-cadherin and alpha-catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta-catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E-cadherin and beta-catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E-cadherin, alpha-catenin and beta-catenin are related events. Furthermore, expression of at least E-cadherin and beta-catenin is significantly correlated with poor prognosis.

Adenocarcinoma

Choledochocele presenting with anaemia.

A 31-year-old man presented with abdominal pain and iron deficiency anaemia due to gastrointestinal blood loss. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a choledochocele, located between the ampullary sphincter and the sphincters of the common bile duct and pancreatic duct. The choledochocele was removed surgically and appeared to be covered with duodenal mucosa. Gastrointestinal blood loss is explained by the extensive erosions found in the duodenal mucosa of the choledochocele. Choledochoceles should be treated by radical resection.

Abdominal Pain

Benign anastomotic strictures after transhiatal esophagectomy and cervical esophagogastrostomy: risk factors and management.

UNLABELLED: Benign stricture formation at the cervical anastomosis after transhiatal esophagectomy with gastric tube interposition is an important source of morbidity. In a large group of patients (n = 269) who had undergone transhiatal esophagectomy with gastric tube interposition, we examined surgical and nonsurgical risk factors for the development of benign strictures at the cervical anastomosis. In addition, we evaluated the results of endoscopic bougie dilation in patients in whom an anastomotic stricture developed. RESULTS: During follow-up, 114 patients (42%) had a benign anastomotic stricture. Only a history of cardiac disease (P = 0.03), postoperative leakage at the anastomosis (p = 0.002), and a stapled rather than a hand-sewn anastomosis (p = 0.04) were found to be independent risk factors for the development of a stricture. In 27 of 60 patients with anastomotic leakage, contrast swallow examination demonstrated only a leak at the anastomosis. Endoscopic bougie dilation of anastomotic strictures was successful in 78% of patients after a median of three dilation sessions (range 1 to 28). In 3% of patients dilations were still being performed, and 19% of patients had died before normal swallowing had been achieved. In two of 519 (0.4%) dilation sessions a major complication occurred. CONCLUSIONS: (1) Patients with preoperative cardiac disease are at an increased risk for anastomotic stricture. (2) Even in patients having no symptoms, a contrast swallow can detect anastomotic leakage that results in an increased risk for the development of anastomotic strictures. (3) The benefit of the stapler device for anastomosis remains to be determined. (4) Endoscopic bougie dilation with the patient mildly sedated is a safe and effective method for the treatment of anastomotic strictures.

Adult

Cytogenetic analysis of Barrett's mucosa and adenocarcinoma of the distal esophagus and cardia.

We performed flow cytometry and cytogenetic analysis of 37 adenocarcinomas of the distal esophagus and cardia, of which 22 arose in Barrett's mucosa. Two of eight analyzed specimens of Barrett's mucosa had clonal chromosomal abnormalities. In 19 cases clonal chromosomal abnormalities were found in tumor tissue. The complex pattern of cytogenetic changes did not differ among the adenocarcinomas arisen in Barrett's esophagus, and those in the distal esophagus without Barrett's mucosa or cardia. Abnormal karyotypes with multiple and complex rearrangements were seen in 11 cases and with single or a few numeric changes in eight. Losses of chromosomes 4, 18, 21, and Y were the most frequent numeric changes. Loss of the Y chromosome was observed in eight of 26 tumors of males (31%). Gains of chromosomes 14 and 20 were also frequent numeric changes. Structural abnormalities were observed in 13 of the abnormal karyotypes (68%). The chromosome arms most frequently rearranged were 1p, 3q, 11p and 22p. The chromosome arm most frequently contributing to losses was 1p, with the shortest region of overlap being 1p22-33. The chromosome arms most often involved in gains were 11p and 22p, and i(3q) was the isochromosome that was most frequently identified.

Adenocarcinoma

Neoadjuvant treatment in oesophageal cancer: the needs for future trials. The Rotterdam Esophageal Tumor Study Group.

In view of the poor survival after surgery alone for oesophageal cancer, combination with chemotherapy seems rational. A concept of upfront chemotherapy is discussed and seems especially useful for these tumours. The published randomized trials, studying the effect of neoadjuvant chemotherapy do, however, not (yet) show an improved overall survival, apart from one study with a significant median survival benefit at an interim evaluation. The responding patients have in all trials a far better survival than the non-responders. The numbers of patients are small and results of other ongoing and future trials should be awaited. New trials testing high-dose chemotherapy with bone marrow support should be initiated.

Antineoplastic Combined Chemotherapy Protocols

Cisplatin and etoposide in oesophageal cancer: a phase II study. Rotterdam Oesophageal Tumour Study Group.

In the search for effective chemotherapy regimens which can be used in multimodality treatment programmes for patients with cancer of the oesophagus, we conducted a phase II trial to determine the activity and toxicity of the combination of cisplatin and etoposide in patients with advanced squamous cell carcinoma of the oesophagus. Seventy-three consecutive patients with unresectable or metastatic squamous cell carcinoma of the thoracic oesophagus were treated with cisplatin 80 mg m-2 by 4 h infusion on day 1, etoposide 100 mg (fixed dose) by 2 h infusion on day 1 and 2, and etoposide 200 mg m-2 orally on day 3 and 5. Courses were repeated every 4 weeks, for a maximum of six courses. The oral dosages of etoposide were modified individually until a significant degree of myelosuppression was reached. Of 65 evaluable patients, five complete responses (CRs) and 26 partial responses (PRs) were seen, for an overall response rate of 48% (95% confidence interval 35-60%). Median time to progression was 7 months (range 3-72 + months). There were two toxic deaths (neutropenic sepsis). The response rate equals that of other cisplatin-based regimens. Its toxicity profile allows addition of a third active drug such as 5-fluorouracil.

Adult

Intragraft IL-4 mRNA expression is associated with down-regulation of liver graft rejection.

The mechanism underlying spontaneously resolving allograft rejection following clinical liver transplantation is unidentified. In this process, immunoregulatory T helper (Th)-2 cytokines like IL-4, often identified with down-regulation of the Th1-dependent (IL-2) cell-mediated response, might play a significant but unknown role. For this reason, we analyzed mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in 57 biopsies derived from 19 recipients. Specimens included biopsies without evidence of rejection (n = 36), biopsies with histological evidence of rejection (n = 10) not followed by clinical signs of graft rejection, and biopsies with histological rejection that were accompanied with clinical rejection (n = 11), defined by rising serum bilirubin and aspartate amino transaminase (ASAT) levels. Intragraft IL-4 mRNA expression significantly correlated with spontaneously resolving rejections. In 70% (7/10) of these biopsies, IL-4 mRNA was detectable, while only 19% (7/36) of the biopsies without signs of rejection (p < 0.01; Fisher's exact test) and 18% (2/11) of the rejection biopsies concurrent with graft dysfunction expressed the IL-4 gene (p = 0.03). In contrast, IL-2 mRNA expression was not detectable in biopsies derived from the spontaneously resolving rejections. None (0/10) of these samples expressed the IL-2 gene, which was not significantly different from the proportion of biopsies transcribing the IL-2 gene in the absence of rejection (11%, 4/36). IL-2 mRNA expression was found more often in biopsies associated with graft dysfunction (36%, 4/11). These results show that IL-4, in contrast to IL-2 mRNA expression, is associated with spontaneously resolving liver rejection. This suggests that Th2 cells down-regulate the Th1-dependent cell-mediated immune response after clinical liver transplantation.

Aspartate Aminotransferases

Accumulation of genetic abnormalities during neoplastic progression in Barrett's esophagus.

Sex chromosome status, ploidy, and proliferation rate were evaluated in archival material of 73 Barrett's esophagus patients (48 males and 25 females). Diagnosis in esophageal mucosa samples ranged from intestinal metaplasia with no dysplasia to invasive esophageal adenocarcinoma; also, four lymph node metastases were studied. Chromosomal and ploidy aberrations were determined by in situ hybridization with repetitive DNA probes specific for chromosomes Y, X, and 1. Proliferation index (Ki-67 protein expression) was assessed by immunohistochemistry. Proliferation rate was elevated in all stages of dysplasia and in the adenocarcinomas. Aneuploidy (hyperdiploidy) and loss of the Y chromosome correlated with the advancing stages toward neoplasia (P < 0.001) and reached high prevalences (70-100%) in high-grade dysplasia and adenocarcinoma. Abnormalities of the X chromosome were not seen. These data suggest that in Barrett's esophagus, genetic perturbations may be generated in relation to a high proliferation rate.

Adenocarcinoma

Budd-Chiari syndrome.

Budd-Chiari syndrome is the generic term for different forms of hepatic venous outflow obstruction resulting in a clinical picture of portal hypertension and hepatomegaly. Three levels of venous outflow obstruction may be recognized, affecting respectively the small intrahepatic (IVC). Each level of obstruction is related to a different aetiology. Clinical manifestations range from mild symptoms to acute or chronic end-stage liver disease. Treatment is surgical in the great majority of patients. Occlusion of the IVC may be treated by removal of the caval obstruction in selected patients. Hepatic outflow obstruction may be circumvented by different forms of shunting from the portal or upper mesenteric vein to the IVC or right atrium, depending on the level of obstruction and the difference in venous pressure. For the rare patient presenting with acute or chronic end-stage liver failure, hepatic transplantation may be a life-saving procedure.

Arteriovenous Shunt, Surgical

Accumulation of p53 protein in normal, dysplastic, and neoplastic Barrett's oesophagus.

Accumulation of p53 protein was determined by immunohistochemistry in archival material of biopsy specimens from 102 patients with Barrett's oesophagus with different grades of dysplasia, in 24 oesophageal adenocarcinomas associated with Barrett's oesophagus, and in 23 cases of metaplastic epithelium adjacent to these carcinomas. Immunostaining for the p53 protein was found in 23/102 (23 per cent) cases of the Barrett's oesophagus biopsies and in 12/23 (52 per cent) cases of Barrett's oesophagus adjacent to adenocarcinoma. Significant correlations were found between the grade of dysplasia and p53 immunoreactivity in both Barrett's biopsies without adenocarcinoma (P < 0.001) and Barrett's oesophagus adjacent to adenocarcinoma (P < 0.05). In the adenocarcinomas, intense nuclear immunohistochemical staining for p53 was diffusely or focally present in 20/24 (83 per cent) of the specimens. In Barrett's oesophagus, p53 is a progression marker with high expression in high-grade dysplasia (89 per cent) and adenocarcinoma (83 per cent).

Adenocarcinoma

Early detection and treatment of oesophageal and gastric cancer. The Rotterdam Oesophageal Tumour Study Group.

Early oesophageal and gastric cancer are unique forms of oesophageal and gastric carcinoma with an excellent prognosis. Remarkable changes have taken place in the epidemiology of upper gastrointestinal malignancies. In particular, the incidence of adenocarcinoma of the distal oesophagus and the gastric cardia has risen over the past two decades. In the United States and Europe, early detection is dependent on a low threshold for upper gastrointestinal endoscopy with biopsy, because specific symptoms and physical findings are rarely present in patients with early oesophageal and gastric cancer. In addition to histology, the detection of possible markers of malignancy, such as aneuploidy (detected by flow cytometry) and the presence of oncogenes and tumour-suppressor genes, in biopsy material may be of value in the diagnosis of early cancers. For patients with early oesophageal or gastric cancer, surgery offers the best hope of cure. If patients are at high risk for surgery, an endoscopic resection may be an alternative option. This review discusses the definitions, the changes in epidemiology, the current options for diagnosis and treatment, and the value of screening programs for patients with early oesophageal or gastric cancer.

Barrett Esophagus

The influence of age on resection rates and postoperative mortality in 2773 patients with gastric cancer.

Resection rates and postoperative mortality rates were studied in patients with gastric cancer, diagnosed from 1982 until 1992 in the southwestern area of the Netherlands. Overall, 51% of the patients underwent resection. For patients aged 0-59, 60-69, 70-79 and 80 years and over, resection rates were 64, 55, 54 and 35%, respectively. Tumours located in the cardia were less often resected than tumours of the antrum, 39 versus 71%. The postoperative mortality after resectional operations was 8.3%; 9.2% for men and 6.7% for women. The operative risk increased markedly after the age of 70 years; for patients under 70 years of age, the rate was 3.4% compared with 12.4% for those aged 70 years and older. These results indicate that elderly patients can be operated on at an acceptable risk, and that palliative resections may be considered, especially in patients younger than 70 years.

Adolescent

Heterotopic ossification induced by hypoxia in a retrosternal gastric tube following transhiatal oesophagectomy.

A 71 year old man underwent retrosternal gastric tube reconstruction following transhiatal oesophagectomy for squamous cell carcinoma. On the second post-operative day, the patient developed a cardiac arythmia with secondary hypotension followed by hypoxaemia necessitating artificial ventilation. Two weeks after surgery, endoscopy revealed massive necrosis of the proximal segment of the gastric tube extending from the anastomosis in the neck to the watershed area. Three weeks later, the patient died and a necropsy was performed. Macroscopic evaluation of the gastric tube revealed a sharply demarcated and fully ossificated proximal segment. Heterotopic ossification was present on histological examination. This condition has only been described in conjunction with primary or metastatic gastric adenocarcinoma. The location of the ossification and the presence of temporary systemic hypoxia suggest that the latter was the main factor responsible for the ossificative response.

Aged

Changing patterns in the treatment of carcinoma of the esophagus.

BACKGROUND: Decision-making in esophageal carcinoma. Treatment of carcinoma of the esophagus knows a great variety of modalities, ranging from simple palliative endoscopic pertubation to extensive curative operations. METHODS: Retrospective review. RESULTS: The three main groups of tumors are squamous cell carcinoma related to alcohol and tobacco abuse; adenocarcinoma in Barrett's esophagus related to long-standing gastroesophageal reflux; and adenocarcinoma of the cardia the origin of which is still unknown. Dysphagia and retrosternal pain are not only the most important symptoms but also the most important factors regarding survival. Diagnosis is made by endoscopy and biopsy. In the pretreatment staging a careful selection of the great variety of available diagnostic tools should be made. The ever-increasing diversity of local palliative procedures: tubing, photoablation, brachytherapy all have their place, but should not be allowed to distract us from the fact that surgery is the only hope for cure in these patients. Surgery should only be performed with curative intent and even then the long-term results are modest, with a 5-year survival of about 40% in node-negative and 18% in node-positive patients. CONCLUSION: In patients with carcinoma of the esophagus a polydisciplinary treatment approach is mandatory.

Combined Modality Therapy

Prognostic value of p53 in Barrett's oesophagus.

During the last 30 years, the incidence of oesophageal adenocarcinoma has increased rapidly. Patients with Barrett's oesophagus have an increased risk of developing oesophageal adenocarcinoma and should be kept under surveillance. However, only a subset of Barrett's oesophagus patients will eventually develop malignancy and surveillance programs using endoscopy and histopathology cannot efficiently identify this subgroup. The study of additional prognostic factors is therefore of major importance and the p53 tumour suppressor gene has attracted much attention in this respect. Several investigators have found that p53 alteration is a frequent event in oesophageal adenocarcinomas and is associated with malignant transformation of Barrett's oesophagus. p53 appears to be a promising prognostic marker in Barrett's oesophagus and, as research progresses, possible clinical applications are emerging.

Adenocarcinoma

[Criteria for and results of liver transplantation in patients with acute liver insufficiency].

OBJECTIVE: Evaluation of the results of emergency liver transplantation in patients with acute liver failure. DESIGN: Analysis of 25 patients with acute liver failure. SETTING: University Hospital Rotterdam Dijkzigt. METHOD: Twenty-five patients with acute liver failure were admitted to the Intensive Care Unit in January 1989-May 1993. Patients were selected for emergency liver transplantation according to the Clichy criteria (presence of confusion or coma and factor V activity less than 20-30%). RESULTS: Liver transplantation was indicated in 17 patients and performed in 13. The 1-year survival rate in patients with a liver transplant was 85%. Four patients with an indication for liver transplantation, but who could not be transplanted died. All 8 patients without an indication for emergency liver transplantation survived. CONCLUSION: Survival after liver transplantation for acute hepatic failure is now about 80%; the Clichy criteria appear to be helpful in selecting patients with acute hepatic failure for liver transplantation.

Adolescent