Search PubMed⌕ Search

Biomedical subjects

H W Tilanus

Publications and source records attributed to H W Tilanus.

At least 37 records · Page 2Linked to original sources
PubMed2003

Prognostic factors for survival in patients with advanced oesophageal cancer treated with cisplatin-based combination chemotherapy.

The objective of this study was to identify prognostic factors for survival in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy. We analysed the baseline characteristics of 350 patients who were treated in six consecutive prospective trials with one of the following regimens: cisplatin/etoposide, cisplatin/etoposide/5-fluorouracil, cisplatin/paclitaxel (weekly) and cisplatin/paclitaxel (biweekly). Predictive factors in univariate analyses were further evaluated using multivariate analysis (Cox regression). The median survival of all patients was 9 months. The 1, 2 and 5-year survival rates were 33, 12 and 4%, respectively. The main prognostic factors were found to be WHO performance status (0 or 1 vs 2), lactate dehydrogenase (normal vs elevated), extent of disease (limited disease defined as locoregional irresectable disease or lymph node metastases confined to either the supraclavicular or celiac region vs extensively disseminated disease) in addition to the type of treatment (weekly or biweekly cisplatin/paclitaxel regimen vs 4-weekly cisplatin/etoposide with or without 5-fluorouracil). Although weight loss, liver metastases and alkaline phosphatase were significant prognostic factors in univariate analyses, these factors lost their significance in multivariate analyses. The median survival for patients without any risk factors was 12 months, compared to only 4 months in patients with WHO 2 plus elevated LDH and extensive disease. The performance status, extent of disease, LDH and the addition of paclitaxel to cisplatin are independent prognostic factors in patients with advanced oesophageal cancer, who are treated with cisplatin-based combination chemotherapy.

Adenocarcinoma↗
PubMed2003

Good outcomes after resection of large hepatocellular carcinoma in the non-cirrhotic liver.

BACKGROUND: The results of partial liver resection of hepatocellular carcinoma (HCC) in non-cirrhotic livers are not well known. Therefore a retrospective study was conducted. METHODS: The medical records of 180 patients with HCC were reviewed. In 40 patients (22%), HCC occurred in a non-cirrhotic liver. A detailed analysis of these patients was performed. The diagnosis HCC was based on imaging and/or percutaneous ultrasound-guided biopsy. A biopsy of the remaining liver and peroperative findings documented the absence of cirrhosis. RESULTS: Twenty-two patients underwent partial liver resection. There was no surgical mortality. The median tumour diameter in the operated patients was 10 cm. Survival rates for operated patients at 1 and 5 years were 96 and 68%, respectively. Significant factors reducing survival were portal vein thrombosis, positive lymph nodes, microscopic vascular invasion and tumour recurrence. Tumour size at the initial moment of diagnosis was not of predictive value. After surgery with curative intent disease-free interval at 1 and 5 years were 86 and 56%, respectively. CONCLUSION: In selected patients without cirrhosis, HCC can be treated successfully by surgical resection, independent of the tumour diameter, with a 5-year survival rate of 68%.

Adult↗
PubMed2003

[Transhiatal or transthoracic resection of esophageal carcinoma based on tumor location, positive high-thoracic lymph nodes and preoperative physical condition].

The limited transhiatal resection for the surgical treatment of oesophageal cancer is aimed at limiting early postoperative complications by not performing lateral thoracotomy and formal lymphadenectomy. The extended transthoracic approach with two-field lymphnode dissection is intended to improve long-term survival. The recurrence pattern after transhiatal resection suggests that a subgroup of patients might benefit from the more extended approach. In a large randomized trial in two high-volume Dutch academic hospitals, extended resection resulted in more postoperative (pulmonary) complications and a prolonged postoperative recovery time, but when compared to transhiatal resection, had only a limited impact on quality of life. The estimated 5-year survival advantage after extended resection was 10% (95% confidence interval: -3% to +23%). Subgroup analysis indicated a 17% 5-year survival advantage for patients with oesophageal cancer, but only a 1% advantage for patients with cancer of the cardia or gastro-oesophageal junction. The individualized operative approach for patients with potentially curable oesophageal cancer is based on tumour location, positive high-thoracic lymph nodes and preoperative physical condition.

Carcinoma↗
PubMed2003

[Diagnosis and treatment of esophageal cancer in the Netherlands: wide variation in the second line].

OBJECTIVE: To survey the diagnostic procedures and treatment strategies currently employed in hospitals for patients with oesophageal cancer. DESIGN: Questionnaire. METHOD: A questionnaire was sent to all clinicians working in the field of gastroenterology in the Netherlands. This questionnaire focused on clinical preferences regarding diagnostic procedures and treatment strategies for oesophageal cancer. Also, six hypothetical patient vignettes were presented in order to investigate which factors affected choice of treatment, in particular surgical treatment. RESULTS: The response rate was 64% (426/667); 336 questionnaires were relevant to the investigation. Almost 90% of the clinicians treated fewer than 20 patients annually, usually in their own hospital. CT was the most frequently used staging procedure; endoscopic ultrasound was less frequently used (42% used it in less than half the patients). The treatment choice for the patient vignettes varied widely among clinicians. Factors influencing the choice to operate or not were: metastases, loco-regional tumour ingrowth, poor general health, and advanced age with 8, 22, 20, and 53%, respectively, of the clinicians still considering surgery in the presence of one of these factors as opposed to 99% if none of these factors were present. Surgeons opted for operation more often than internists and gastroenterologists. Stent placement was the most frequently chosen method to palliate malignant dysphagia. CONCLUSION: There is a wide variation in the use of diagnostic procedures and treatment strategies for patients with oesophageal cancer in the Netherlands. This stresses the need for scientifically based practice guidelines, taking into account specific patient and tumour characteristics.

Aged↗
PubMed2003

Expression of CD80 on Kupffer cells is enhanced in cadaveric liver transplants.

In experimental animals inhibition of T cell co-stimulation immediately after organ transplantation effectively prevents rejection. We investigated whether the expression of co-stimulatory molecules is enhanced in cadaveric liver transplants, whether their expression is influenced by the transplantation procedure, and whether variation in expression between liver transplants is related to the occurrence of acute rejection. Expression of CD80, CD86 and the macrophage marker CD68 were determined by immunohistochemistry in biopsies from 40 clinical liver transplants obtained at different time-points during the transplantation procedure, and in normal liver tissue obtained from 10 human livers. Expression of CD80 and CD86 on Kupffer cells was graded by comparison with CD68-staining. In a subgroup CD80 and CD86 mRNA was quantified by real-time detection polymerase chain reaction. CD86 was expressed in all liver transplants and normal livers on the majority of Kupffer cells. CD80 was absent or sporadically expressed in normal liver tissue, but in 18 of 40 liver transplants at least one-quarter of Kupffer cells expressed CD80. CD80- and CD86-mRNA and protein expression in liver transplants did not change during the warm ischaemic and reperfusion phases of the transplantation procedure. CD80-expression on Kupffer cells varied strongly between individual donor livers; this variation was, however, not significantly related to the occurrence of acute rejection after transplantation. In conclusion, in nearly half of cold-preserved cadaveric liver transplants an increased proportion of Kupffer cells express CD80 at the time of transplantation in comparison with normal liver tissue. The expression was not further induced by warm ischaemia and reperfusion. However, the observed variation in CD80-expression between liver transplants is not a accurate predictive measure for acute rejection.

Adult↗
PubMed2003

Phase II study of neo-adjuvant chemotherapy with paclitaxel and cisplatin given every 2 weeks for patients with a resectable squamous cell carcinoma of the esophagus.

BACKGROUND: We have previously reported a favourable response rate in patients with advanced esophageal cancer after treatment with a biweekly regimen of paclitaxel and cisplatin. In this study we investigate the feasibility and efficacy of this regimen in a neo-adjuvant setting. PATIENTS AND METHODS: Patients with resectable squamous cell carcinoma of the esophagus received paclit-axel 180 mg/m(2) and cisplatin 60 mg/m(2) every 2 weeks. Patients received three courses and responding patients received three additional courses; thereafter, patients were referred for surgery. Patient characteristics of 50 eligible patients were as follows: male, 60%; median age, 62 years (range 45-78); median World Health Organization performance status of 1 (range 0-2). RESULTS: Ninety-four per cent of patients received at least three courses of chemotherapy. Haematological toxicity consisted of National Cancer Institute-Common Toxicity Criteria grade 3 or 4 neutropenia in 71% of patients, with neutropenic fever occurring in only two patients (4%). The overall response rate was 59%. Pathological examination showed tumour-free margins in 38 patients. In seven patients no residual tumour was found. The median overall survival was 20 months and the 1- and 3-year survival rates were 68% and 30%, respectively. CONCLUSIONS: This dose-dense schedule of paclitaxel and cisplatin administered biweekly is well tolerated and the observed overall and complete response rates are promising.

Aged↗
PubMed2003

Monitoring in situ dosimetry and protoporphyrin IX fluorescence photobleaching in the normal rat esophagus during 5-aminolevulinic acid photodynamic therapy.

Experimental therapies for Barrett's esophagus, such as 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), aim to ablate the premalignant Barrett's epithelium. However, the reproducibility of the effects should be improved to optimize treatment. Accurate irradiation with light of a proper wavelength (633 nm), fluence and fluence rate has shown to be critical for successful ALA-PDT. Here, we have used in situ light dosimetry to adjust the fluence rate measured within the esophagus for individual animals and monitored protoporphyrin IX (PpIX) fluorescence photobleaching simultaneously. Rats were administered 200 mg kg-1 ALA (n = 14) or served as control (n = 7). Animals were irradiated with an in situ measured fluence rate of 75 mW cm-2 and a fluence of 54 J cm-2. However, this more accurate method of light dosimetry did not decrease the variation in tissue response. Large differences were also observed in the dynamics of PpIX fluorescence photobleaching in animals that received the same measured illumination parameters. We found that higher PpIX fluorescence photobleaching rates corresponded with more epithelial damage, whereas lower rates corresponded with no response. A two-phased decay in PpIX fluorescence could be identified in the response group, with a rapid initial phase followed by a slower rate of photobleaching. Non-responders did not show the rapid initial decay and had a significantly lower rate of photobleaching during the second phase of the decay (P = 0.012).

Aminolevulinic Acid↗
PubMed2002

Liver transplantation and hepatitis C.

End-stage liver disease caused by chronic hepatitis C viral infection is one of the major indications for liver transplantation. However, evidence for ongoing viral replication can already be found days after surgery and may lead sequentially to lobular hepatitis, chronic active hepatitis, fibrosis and liver cirrhosis. In some patients, this evolution is remarkably fast, most probably enhanced by the immunosuppressive therapy. A minority of patients develop a clinical picture of progressive cholestatic liver disease with histological signs of chronic rejection, which may necessitate retransplantation. While the 1- and 5-year survival rates for all patients transplanted because of hepatitis C virus (HCV)-induced liver cirrhosis are satisfactory, severe complications of disease recurrence are nonetheless expected during the first and second decade after liver transplantation. Larger and preferably randomized studies are needed to investigate whether combination therapy with interferon and ribavirin, preferably initiated as soon as possible after liver transplantation, prevents the fast evolution to cirrhosis without the appearance of chronic rejection and the expected complications of recurrent end-stage HCV-induced liver disease. The final goal should be the inhibition of viral replication even before liver transplantation, but other antiviral strategies should probably be used to attain this goal in patients with decompensated cirrhosis. Although the recurrence of a hepatitis C infection and concomitant disease in the liver graft may cause substantial morbidity, end-stage liver disease and liver failure caused by a chronic hepatitis C infection remain good indications for liver transplantation.

Antiviral Agents↗
PubMed2002

Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer.

In a phase I study we demonstrated the feasibility of a bi-weekly combination of paclitaxel 180 mg x m(-2) with cisplatin 60 mg x m(-2). In this study we further assessed toxicity and efficacy of this schedule in the treatment of advanced cancer of the oesophagus or the gastro-oesophageal junction. Patients received paclitaxel 180 mg x m(-2) administered over 3 h followed by a 3-h infusion of cisplatin 60 mg x m(-2). Patients were retreated every 2 weeks unless granulocytes were <0.75x10(9) or platelets <75x10(9). Patients were evaluated after three and six cycles and responding patients received a maximum of eight cycles. Fifty-one patients were enrolled into the study. The median age was 56 years (range 32-78). WHO performance status were: 0 (19 patients); 1 (29 patients); 2 (three patients). All patients received at least three cycles of chemotherapy and all were evaluable for toxicity and response. Haematological toxicity consisted of uncomplicated neutropenia grade 3 in 39% and grade 4 in 31% of patients. Five patients (10%) were hospitalised, three patients because of treatment related complications and two patients because of infections without neutropenia. Sensory neurotoxicity was the predominant non-haematological toxicity; grade 1 and 2 neurotoxicity was observed in 43 and 20% of patients, respectively. Response evaluation in 51 patients with measurable disease: complete response 4%, partial response 39%, stable disease 43% and progressive disease in 14% of the patients. The median duration of response was 8 months. The median survival for all patients was 9 (range 2-29+) months and the one-year survival rate was 43%. Four patients who received additional local treatment (two patients surgery and two patients radiotherapy) are still disease free after a follow-up of 20-29 months. This bi-weekly treatment of paclitaxel and cisplatin is well tolerated by patients with advanced oesophageal cancer. The toxicity profile of this regimen compares favourable to that of previously used cisplatin- and paclitaxel-based regimens. Trials are underway evaluating this bi-weekly regimen in a neo-adjuvant setting.

Adenocarcinoma↗
PubMed2002

[The treatment of colorectal liver metastases: good 5 year survival chance after partial liver resection at the Rotterdam University Hospital, 1984/1999].

OBJECTIVE: To evaluate the results of partial liver resection in patients with liver metastases. DESIGN: Retrospective. METHOD: All of the patients who underwent a partial liver resection at the Rotterdam University Hospital during the period June 1984-August 1999 due to one or more metastases of a colorectal carcinoma were traced in the computerised hospital archive. Data concerning the primary tumour, the diagnostics carried out, the liver resection carried out and the clinical outcome after the operation were analysed using the statistical software SPSS. The actuarial survival was determined according to the Kaplan-Meier method. RESULTS: In total 163 patients underwent an operation: 108 men and 55 women, with a mean age of 58 years (range: 32-77). Postoperative morbidity occurred in 34 patients (21%), mostly infections and gall leakage. During the hospital admission 10 patients died (6%). In the follow-up period, mean 30.2 months (median: 23.8) there was a recurrence of colorectal carcinoma in 82 of the patients (50%). The actuarial 5-year survival chance was 37%. The only statistically significant unfavourable prognosis factor for survival, was a larger tumour volume in the liver at the time of the hepatectomy.

Adult↗
PubMed2002

Phase I study of a weekly schedule of a fixed dose of cisplatin and escalating doses of paclitaxel in patients with advanced oesophageal cancer.

The objective of this study was to determine the toxicities and maximum tolerated dose (MTD) of a dose-dense schedule with a fixed dose of cisplatin and escalating doses of paclitaxel in patients with metastatic or irresectable squamous cell-, adeno-, or undifferentiated carcinoma of the oesophagus. Patients received paclitaxel over 3 h followed by a 3-h infusion of a fixed dose of cisplatin of 70 mg/m(2) on days 1, 8, 15, 29, 36 and 43. The starting dose of paclitaxel was 80 mg/m(2). Patients were re-treated if white blood cell count (WBC) was >/=1 x 10(9) cells/l, except for day 29 when the WBC had to be >/=3 x 10(9) cells/l. Six patients were treated at each dose level. The dose of paclitaxel was increased by 10 mg/m(2) per level. Of the 24 patients enrolled, 13 had adenocarcinoma, 10 had squamous cell carcinoma and one had an undifferentiated carcinoma. All patients were evaluable for toxicity and 22 of 24 patients were evaluable for response. The paclitaxel dose could be escalated to 110 mg/m(2). At this dose, 3 out of 6 patients developed dose-limiting toxicity (DLT) including neutropenic enterocolitis with sepsis, vomiting and diarrhoea. Diarrhoea grades 3 and 4 was seen in 4 (17%) patients. Two of these patients died of neutropenic enterocolitis. Neutropenia grades 3 or 4 was seen in 20 (83%) patients, but apart from the two patients with neutropenic enterocolitis no other infectious complications were seen. Mild to moderate sensory neurotoxicity was seen in 11 (46%) patients (grade 1 in 8 patients and grade 2 in 3 patients). Other toxicities were mild and easily manageable. Of the 22 evaluable patients, 11 (50%) patients achieved a partial or complete response with a median duration of 13 months. Ten patients with either locally advanced disease or supraclavicular or celiac lymph nodes received additional local treatment after response to chemotherapy, seven patients are still without evidence of disease after a median follow-up of 32 months. Paclitaxel at a dose 100 mg/m(2) infused over 3 h followed by a 3-h infusion of 70 mg/m(2) cisplatin can be recommended for further studies in patients with metastatic or unresectable oesophageal cancer. Occurring diarrhoea should be handled with caution because it may be a sign of neutropenic enterocolitis. The response rate of this dose-dense schedule seems encouraging.

Adenocarcinoma↗
PubMed2002

Size of lesion is not a criterion for resection during management of giant liver haemangioma.

BACKGROUND: The unknown natural history and risk of complications of large haemangiomas may pose therapeutic dilemmas. The authors describe their experience with the management of giant haemangiomas. METHODS: Patients with a giant haemangioma were identified by a survey of the hospital database. Forty-nine patients with a haemangioma of at least 4 cm in diameter presented between January 1990 and December 2000. Medical records were analysed retrospectively. RESULTS: Eleven patients had surgical treatment and 38 were managed conservatively. The median diameter of the tumours was 8.0 cm in surgically treated patients and 6.0 cm in the group managed by observation. Surgery-related morbidity occurred in three patients, and abdominal complaints persisted in three of ten patients with a symptomatic lesion. During a median follow-up of 52 months, 12 non-operated patients had mild abdominal complaints, considered to be unrelated to the lesion. In these patients symptoms either diminished or became minimal during follow-up. Complications did not occur. CONCLUSION: Observation of giant haemangiomas can be performed safely. The authors advocate resection of cavernous liver haemangiomas only in patients with persistent severe symptoms.

Adult↗
PubMed2001

Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor gamma tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction.

We investigated whether 2 candidate tumor-suppressor genes, VHL at 3p25-26 and PPAR gamma at 3p24.2-25, are involved in GEJ adenocarcinogenesis. In 43 GEJ tumor samples from 40 patients, the entire coding sequence of the VHL gene and the 5' and part of the 3' UTR as well as exons 3 and 5 of the PPAR gamma gene were screened by PCR-SSCP analysis. LOH at 3p25-26 was analyzed with 2 polymorphic microsatellite markers and with the VHL exon 1 and intron 2 polymorphisms. The relationship between LOH and clinicopathologic parameters was assessed. Expression of VHL was investigated by immunohistochemistry with a VHL-specific antibody. PCR-SSCP analysis of VHL revealed 2 different aberrant patterns in 19 patients. Upon DNA sequencing, 1 pattern appeared to be a previously described exon 1 polymorphism. The other single aberrant pattern was an intron 2 polymorphism, not yet described. PCR-SSCP analysis of PPAR gamma showed no aberrant migration patterns. LOH analysis revealed 3p25-26 loss in 24/36 (67%) informative cases, but this was not significantly correlated with clinicopathologic parameters. By immunohistochemistry, all tumors showed expression of VHL protein. Despite the very frequent LOH of 3p in GEJ adenocarcinomas, mutations in VHL and PPAR gamma were not detected. Mutations outside the screened sequences, a gene dosage effect or involvement of another tumor-suppressor gene on 3p as the target of LOH should be considered.

Adenocarcinoma↗
PubMed2001

[Consequences of caustic damage of the esophagus].

Following ingestion of a highly concentrated acetic acid solution, three women aged 29, 23 and 25 years old, suffered damage to the oesophagus and the stomach, respiratory and renal insufficiency and haemolysis. After intensive treatment, gastric tube reconstruction was carried out in 2 of these patients, and the third woman required repeated dilatations of the oesophageal stricture from 6 weeks after ingestion onwards. This resulted in a normal passage of solid food in all women. A 58-year-old man who had ingested caustic soda at 4 years of age, presented with increasing problems associated with swallowing food. A squamous cell carcinoma was diagnosed and treated with chemotherapy, oesophagus-cardia resection and gastric tube reconstruction. After 2 years the tumour has not recurred. Ingestion of corrosive substances can lead to serious damage of the gastrointestinal tract. Early endoscopy is important in establishing the extent of the injury. During the acute phase, intensive care admittance is often necessary and resection of the oesophagus is also necessary in some cases. Subsequent treatment can vary from endoscopic dilations to gastric tube reconstruction following resection of the oesophagus.

Acetic Acid↗
PubMed2001

Hospital volume and hospital mortality for esophagectomy.

BACKGROUND: Hospital mortality after esophagectomy has decreased from 29% to 7.5% over the last decades because of improved surgical techniques and better perioperative care. Suggestions have been made that a further decrease in hospital mortality may be achieved by centralization of esophagectomies in high volume centers. METHODS: The effect of hospital volume on hospital mortality after esophagectomy in the Netherlands was analyzed based on data from the Dutch National Medical Registry and the Dutch Network and National Database for Pathology over the period 1993-1998. RESULTS: Annually, approximately 310 (range, 264-321) esophagectomies are performed in the Netherlands. Fifty-two percent are performed in 43-55 low volume centers (1-10 resections a year). Six percent are performed in 1-3 medium volume centers (11-20 resections a year). The remainder (42%) is performed in two high volume centers (> 50 resections a year). Hospital mortality is 12.1%, 7.5% and 4.9% respectively (P < 0.001). The high volume centers seem to see slightly more advanced tumors than the low and medium volume centers. CONCLUSIONS: There is a significant (inverse) relation between hospital mortality and hospital volume for esophageal resection in the Netherlands. Although hospital mortality is not the only measure for quality of care, these data suggest a potential beneficial effect to centralization of esophagectomy in the Netherlands.

Aged↗
PubMed2001

Genomic alterations in malignant transformation of Barrett's esophagus.

The incidence of adenocarcinoma in Barrett's esophagus has been increasing rapidly over the past decades. Neoplastic progression is characterized by three well-defined premalignant stages: metaplasia, low-grade dysplasia, and high-grade dysplasia. A genome-wide overview, based on comparative genomic hybridization, was performed, evaluating 30 Barrett's adenocarcinomas and 25 adjacent precursors, i.e., 6 metaplasias, 9 low-grade dysplasias, and 10 high-grade dysplasias. The frequency of losses and gains significantly increased in the subsequent stages of malignant transformation. Losses of 5q21-q23, 9p21, 17p12-13.1, 18q21, and Y were revealed in low-grade dysplasias. This was followed by loss of 7q33-q35 and gains of 7p12-p15, 7q21-q22, and 17q21 in high-grade dysplasias along with high-level amplification (HLA) of 7q21 and 17q21. In the invasive cancers, additional losses of 3p14-p21, 4p, 4q, 8p21, 13q14-q31, 14q24.3-q31, 16q21-q22, and 22q as well as gains of 3q25-q27, 8q23-24.1, 12p11.2-12, 15q22-q24, and 20q11.2-q13.1 were distinguished along with HLAs of 8p12-p22 and 20q11.2-q13.1. Approximately one-third of the alterations in the dysplasias were also found in the adjacent adenocarcinomas, illustrating that multiple clonal lineages can be present in Barrett's esophagus. Novel findings include loss on 7q, gain on 12p, and the observation of several HLAs in high-grade dysplasias. Furthermore, loss of 7q33-q35 was found to represent a significant distinction between low-grade and high-grade dysplasia (P = 0.01), whereas loss of 16q21-q22 and gain of 20q11.2-q13.1 were disclosed to significantly discriminate between high-grade dysplasia and adenocarcinoma (P = 0.02 and P = 0.03, respectively). This inventory of genetic aberrations increases our understanding of malignant transformation in Barrett's esophagus and might provide useful biomarkers for disease progression.

Adenocarcinoma↗