Arend Karrenbeld - Academia.edu (original) (raw)
Papers by Arend Karrenbeld
Current Angiogenesis, 2015
Vascular endothelial growth factor-A (VEGFA) and placental growth factor (PlGF) can mediate cance... more Vascular endothelial growth factor-A (VEGFA) and placental growth factor (PlGF) can mediate cancer progression and anticancer treatment failure. We therefore analyzed (sub)cellular patterns of VEGFA and PlGF expression, and mean vessel density (MVD) in primary rectal tumor samples of stage IV patients, who could benefit from improved therapies. VEGFA, PlGF and MVD were measured immunohistochemically in paraffin-embedded rectal tumor tissue before and after pelvic radiotherapy and systemic neoadjuvant treatment with bevacizumab, capecitabine, and oxaliplatin. The relation between baseline expression of VEGFA and PlGF, and MVD and pathologic response to treatment was also analyzed. At diagnosis, 91% of the 46 tumors expressed VEGFA in the cytoplasm and 50% in the nucleus of tumor cells. PlGF was expressed by 74% in the tumor cell's cytoplasm. There were no differences in VEGFA expression and MVD at baseline between the nine patients with pathologic complete response (pCR) and the 30 patients with residual tumor after treatment. All patients with pCR expressed PlGF in tumor cells at baseline, as did 19 of the 30 patients with residual tumor. After treatment, nuclear VEGFA expression in tumor cells and MVD were lower in residual tumors as compared to the initial tumor [15% vs. 56%, P = 0.024, and 10.3 (±4.2) vs.16.4 (±6.0), P < 0.0001]. PlGF expression in residual cancer did not significantly differ from the paired pre-treatment values. These data indicate the relevance of VEGFA and PlGF to rectal tumor biology, and might suggest PlGF blockade as being of interest to test in metastatic rectal cancer.
European Journal of Cancer, Sep 1, 1999
The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian ce... more The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian cells. In its coding region it presents a poly (A) 9 tract, a potential site of mutations in tumors with microsatellite instability (MSI). We analysed the presence of frameshift mutations in the CHK1 gene in MSI+ colorectal and endometrial cancer samples. Other genes reported altered in these tumours (BAX, TGF/~RII, IGFIIR) were also analysed.
European Journal of Cancer Supplements, 2007
Radiotherapy and Oncology, 2015
Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but th... more Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype. 101 EC patients treated with nCRT and surgery were included. Sufficient pre-treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group. Low CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed. Low expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT.
The Netherlands Journal of Medicine, 1995
The American journal of gastroenterology, 2000
It has been suggested that KRAS and TP53 mutated tumors might influence the phenotypic behavior o... more It has been suggested that KRAS and TP53 mutated tumors might influence the phenotypic behavior of left- and right-sided colon tumors. We investigated the incidence of these mutations in left- and right-sided colon tumors and their possible influence on survival in a homogeneous group of patients with Dukes' C colon cancers. The primary tumors of 55 patients with a sporadic Dukes' C colon cancer, all treated with adjuvant chemotherapy were analyzed for the presence of KRAS and TP53 mutations. Mutation detection of the KRAS and TP53 genes was performed on paraffin-embedded tumor material, using denaturating gradient gel electrophoresis. The 5-yr survival rates of KRAS and TP53 mutated tumors were analyzed regarding right-sided tumors (defined as tumors up to the splenic flexure) and left-sided tumors (defined as tumors from the splenic flexure to the rectosigmoid peritoneal reflection). KRAS mutations occurred more frequently in the right colon compared to the left colon (R =...
The Netherlands journal of medicine, 2009
The Netherlands journal of medicine, 2009
Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause ... more Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause of this symptom in 10% of these cases and the prevalence is rising. To exclude microscopic colitis a colonoscopy with multiple biopsies of different regions of the colon is mandatory. A sigmoidoscopy alone is insufficient. Two histopathological types of microscopic colitis can be distinguished: collagenous colitis and lymphocytic colitis. Nowadays, there is sufficient evidence to recommend budesonide as the first-choice treatment. Bismuth can also be recommended, but this drug is not easily available in the Netherlands. Evidence of efficacy of other drugs is scant.
World journal of surgery, 2005
In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver m... more In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver metastases with a carcinoid syndrome, six patients had complaints of postprandial abdominal pain and attacks of subileus based on segmental intestinal ischemia. A diagnosis of abdominal angina was supported by a positive response to nitroglycerin in two and ischemia of the ileum demonstrated by angiography in two other patients. Complaints were reduced in all patients after surgery. Histopathology of the resected small bowel specimens showed elastic vascular sclerosis in three patients and ischemic changes in three other patients, confirming the clinical diagnosis. Resection of ischemic bowel can provide relief in patients with segmental intestinal ischemia caused by carcinoid-induced vascular sclerosis.
![Research paper thumbnail of [Eosinophilic oesophagitis in young men with food swallowing complaints]](https://attachments.academia-assets.com/44058327/thumbnails/1.jpg)
](Nederlands tijdschrift voor geneeskunde, Jan 9, 2005
Bij dysfagie wordt een belemmering gevoeld van de passage van vast of vloeibaar voedsel door de k... more Bij dysfagie wordt een belemmering gevoeld van de passage van vast of vloeibaar voedsel door de keel of slokdarm. Dysfagie, in sommige gevallen samengaand met impactie van een voedselbrok in de slokdarm, komt veel voor en is vaak reden voor endoscopisch onderzoek van het bovenste deel van de tractus digestivus. 1 Bij dysfagie wordt vaak gedacht aan een maligniteit van de slokdarm. Differentiaaldiagnostisch moet er bij passageklachten ook gedacht worden aan motiliteitsstoornissen (bijvoorbeeld door achalasie of sclerodermie), refluxoesofagitis, peptische stenosen, benigne tumoren en compressie van buitenaf. Een aandoening waar vaak niet aan wordt gedacht is eosinofiele oesofagitis. Wij bespreken hier 3 patiënten die wij zagen met deze aandoening.
![Research paper thumbnail of [Small bowel transplantation as a treatment option for intestinal failure in children and adults]](https://attachments.academia-assets.com/44058328/thumbnails/1.jpg)
](Nederlands tijdschrift voor geneeskunde, Jan 19, 2005
Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an... more Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complicat...
![Research paper thumbnail of [Sodium polystyrene sulfonate (Resonium A) as possible cause of rectal blood loss]](https://attachments.academia-assets.com/44058326/thumbnails/1.jpg)
](Nederlands tijdschrift voor geneeskunde, 1997
A 67-year-old man underwent laparotomy for a ruptured aneurysm of the abdominal aorta. Postoperat... more A 67-year-old man underwent laparotomy for a ruptured aneurysm of the abdominal aorta. Postoperatively he was treated with haemodialysis because of perioperatively developed acute renal failure. Hyperkalaemia was temporarily treated with sodium polystyrene sulfonate (Resonium A) after which he lost blood per rectum. A hemicolectomy was necessary because of intractable blood loss due to ulceration of the colon. This complication is related to uraemia and the use of sodium polystyrene sulfonate with or without sorbitol.
The American journal of gastroenterology, 1996
To assess the accuracy of six commonly used diagnostic tests for Helicobacter pylori in a prospec... more To assess the accuracy of six commonly used diagnostic tests for Helicobacter pylori in a prospective study without using any specific test as the gold standard (the patient was regarded as H. pylori-infected if two or more tests, whatever their nature, were positive). In 105 outpatients undergoing upper GI endoscopy, 62 without significant abnormalities, 28 with gastroesophageal reflux disease, 19 with peptic ulcer, one with erosive gastritis, and one with atrophic gastritis (some patients had more than one diagnosis), antral biopsy specimens were taken for culture, polymerase chain reaction, histological examination (hematoxylineosin and Giemsa stains), and rapid urease test. Corpus biopsy specimens were taken for histological examination. Serology (ELISA) and a 13C-urea breath test were also performed. Consistency of diagnosis between two pathologists was assessed by kappa statistics. Sensitivity and specificity, respectively, were as follows: culture, 98.4 and 100%; polymerase c...
Anticancer research
The authors review the result of the selection of patients with a low rectal cancer for pre-opera... more The authors review the result of the selection of patients with a low rectal cancer for pre-operative radiotherapy. The selection was based on the findings of digital examination eventually combined with surgical staging consisting of bimanual palpation during a staging laparotomy or "trial" operation. This selection was used to divide the patients into three groups: one where local radicality could be expected from primary surgery (group 1), one with deeply infiltrating, but mobile tumours requiring 10 x 3 Gy pre-operative radiotherapy (group 2) and one with fixed or borderline resectable tumours requiring protracted pre-operative radiotherapy with 55-59 Gy (group 3). One hundred and one patients were eligible for this study. A resection aiming for pelvic radicality was carried out in 94 patients: primary resection in 38 (group 1), surgery subsequent to 10 x 3 Gy pre-operative radiotherapy in 20 (group 2) and 55-59 Gy in 36 (group 3). The calculated risk of local recurren...
Anticancer research
The aim of this study was to determine the relationship between survival and value of molecular m... more The aim of this study was to determine the relationship between survival and value of molecular markers in the primary tumour in a group of patients with irresectable rectal cancer, treated with preoperative chemo-radiotherapy. Immunohistochemistry for p53, p21, bcl-2 and Ki-67 was performed on pre-treatment biopsy specimens of 34 patients with irresectable rectal cancer. Preoperative treatment consisted of pelvic irradiation of 45-56 Gy, combined with 5FU and leucovorin (350/20 mg/m2 x 5 d; in weeks 1 and 5 during radiotherapy). The median follow-up was 38 months. Endpoints were pathological T-stage and survival after surgery. Expression of p21 correlated significantly with survival (p=0.005). Survival and p21 expression also correlated significantly, when adjusted for tumour response (p=0.005, RR=4.8 (1.6-14.7)). Expression of p21 predicts a worse survival in irresectable rectal cancer treated with preoperative chemo-radiotherapy. No relationship was found between tumour response ...
World journal of gastroenterology : WJG, Jan 7, 2006
Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associate... more Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associated with colorectal and endometrial cancer and a range of other tumor types. Germline mutations in the DNA mismatch repair (MMR) genes, particularly MLH1, MSH2, and MSH6, underlie this disorder. The vast majority of these HNPCC-associated mutations have been proven, or assumed, given the family history of cancer, to be transmitted through several generations. To the best of our knowledge, only a single case of a de novo germline MMR gene mutation (in MSH2) has been reported till now. Here, we report a patient with a de novo mutation in MLH1. We identified a MLH1 Q701X truncating mutation in the blood lymphocytes of a male who had been diagnosed with rectal cancer at the age of 35. His family history of cancer was negative for the first- and second-degree relatives. The mutation could not be detected in the patient' parents and sibling and paternity was confirmed with a set of highly po...
Current pharmaceutical design, Jan 5, 2015
Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling ... more Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling network formed by chemokines and their receptors can promote metastasis and resistance to current anticancer treatments. This study assessed the expression of chemokine receptor 4 (CXCR4) and its ligand CXCL12 immuhistochemically in stage IV rectal tumors. Paraffin-embedded primary tumor collected before and after local radiotherapy and systemic treatment with bevacizumab, oxaliplatin and capecitabine was analyzed. Receptor and ligand expression was assessed in the cytoplasm and nucleus of tumor, stromal and normal rectal crypt cells. Baseline expression of CXCR4 and CXCL12 was correlated with patients' pathologic response to treatment. At diagnosis (n=46), 89% of the rectal tumors expressed cytoplasmic CXCR4 and 81% CXCL12. Nuclear CXCR4 expression in tumor cells was present in 30% and nuclear CXCL12 expression in 35% of the tumors. After radiochemotherapy and bevacizumab, nuclear C...
Hereditary Cancer in Clinical Practice, 2008
H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct t... more H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct ti ic ce e 2008; 6(1)
Human Pathology, 2000
A woman is described who developed an ovarian adenocarcinoma, 3 metachronous colorectal adenocarc... more A woman is described who developed an ovarian adenocarcinoma, 3 metachronous colorectal adenocarcinomas, and a primary adrenocortical adenocarcinoma. Genetic investigation of the mismatch repair genes MLH1 and MSH2 showed a germline mutation in MSH2. Colorectal and ovarian carcinoma belong to the tumor spectrum of hereditary nonpolyposis colorectal cancer (HNPCC). Adrenocortical adenocarcinoma, however, has never been described as 1 of the HNPCC-associated tumors. To investigate whether the adrenocortical adenocarcinoma in this patient was caused by the MSH2 germline mutation, determination of microsatellite instability (MSI) and immunohistochemical analysis were performed on 1 of the colorectal tumors and the adrenocortical adenocarcinoma. MSI and gen-eral loss of MSH2 protein expression could be seen in the colorectal tumor but not in the adrenocortical adenocarcinoma. Therefore, it is highly unlikely that the adrenocortical adenocarcinoma found in this patient was due to her genetic predisposition for HNPCC. HUM PATHOL 31:1522-1527.
Digestive and Liver Disease, 2015
Background: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metapl... more Background: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma. Aim: To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma. Methods: Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival. Results: The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P < 0.001) and high-grade dysplasia (82%, P = 0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients (P = 0.599 and P = 0.700 respectively). Conclusion: GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma.
Current Angiogenesis, 2015
Vascular endothelial growth factor-A (VEGFA) and placental growth factor (PlGF) can mediate cance... more Vascular endothelial growth factor-A (VEGFA) and placental growth factor (PlGF) can mediate cancer progression and anticancer treatment failure. We therefore analyzed (sub)cellular patterns of VEGFA and PlGF expression, and mean vessel density (MVD) in primary rectal tumor samples of stage IV patients, who could benefit from improved therapies. VEGFA, PlGF and MVD were measured immunohistochemically in paraffin-embedded rectal tumor tissue before and after pelvic radiotherapy and systemic neoadjuvant treatment with bevacizumab, capecitabine, and oxaliplatin. The relation between baseline expression of VEGFA and PlGF, and MVD and pathologic response to treatment was also analyzed. At diagnosis, 91% of the 46 tumors expressed VEGFA in the cytoplasm and 50% in the nucleus of tumor cells. PlGF was expressed by 74% in the tumor cell's cytoplasm. There were no differences in VEGFA expression and MVD at baseline between the nine patients with pathologic complete response (pCR) and the 30 patients with residual tumor after treatment. All patients with pCR expressed PlGF in tumor cells at baseline, as did 19 of the 30 patients with residual tumor. After treatment, nuclear VEGFA expression in tumor cells and MVD were lower in residual tumors as compared to the initial tumor [15% vs. 56%, P = 0.024, and 10.3 (±4.2) vs.16.4 (±6.0), P < 0.0001]. PlGF expression in residual cancer did not significantly differ from the paired pre-treatment values. These data indicate the relevance of VEGFA and PlGF to rectal tumor biology, and might suggest PlGF blockade as being of interest to test in metastatic rectal cancer.
European Journal of Cancer, Sep 1, 1999
The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian ce... more The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian cells. In its coding region it presents a poly (A) 9 tract, a potential site of mutations in tumors with microsatellite instability (MSI). We analysed the presence of frameshift mutations in the CHK1 gene in MSI+ colorectal and endometrial cancer samples. Other genes reported altered in these tumours (BAX, TGF/~RII, IGFIIR) were also analysed.
European Journal of Cancer Supplements, 2007
Radiotherapy and Oncology, 2015
Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but th... more Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype. 101 EC patients treated with nCRT and surgery were included. Sufficient pre-treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group. Low CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed. Low expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT.
The Netherlands Journal of Medicine, 1995
The American journal of gastroenterology, 2000
It has been suggested that KRAS and TP53 mutated tumors might influence the phenotypic behavior o... more It has been suggested that KRAS and TP53 mutated tumors might influence the phenotypic behavior of left- and right-sided colon tumors. We investigated the incidence of these mutations in left- and right-sided colon tumors and their possible influence on survival in a homogeneous group of patients with Dukes' C colon cancers. The primary tumors of 55 patients with a sporadic Dukes' C colon cancer, all treated with adjuvant chemotherapy were analyzed for the presence of KRAS and TP53 mutations. Mutation detection of the KRAS and TP53 genes was performed on paraffin-embedded tumor material, using denaturating gradient gel electrophoresis. The 5-yr survival rates of KRAS and TP53 mutated tumors were analyzed regarding right-sided tumors (defined as tumors up to the splenic flexure) and left-sided tumors (defined as tumors from the splenic flexure to the rectosigmoid peritoneal reflection). KRAS mutations occurred more frequently in the right colon compared to the left colon (R =...
The Netherlands journal of medicine, 2009
The Netherlands journal of medicine, 2009
Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause ... more Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause of this symptom in 10% of these cases and the prevalence is rising. To exclude microscopic colitis a colonoscopy with multiple biopsies of different regions of the colon is mandatory. A sigmoidoscopy alone is insufficient. Two histopathological types of microscopic colitis can be distinguished: collagenous colitis and lymphocytic colitis. Nowadays, there is sufficient evidence to recommend budesonide as the first-choice treatment. Bismuth can also be recommended, but this drug is not easily available in the Netherlands. Evidence of efficacy of other drugs is scant.
World journal of surgery, 2005
In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver m... more In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver metastases with a carcinoid syndrome, six patients had complaints of postprandial abdominal pain and attacks of subileus based on segmental intestinal ischemia. A diagnosis of abdominal angina was supported by a positive response to nitroglycerin in two and ischemia of the ileum demonstrated by angiography in two other patients. Complaints were reduced in all patients after surgery. Histopathology of the resected small bowel specimens showed elastic vascular sclerosis in three patients and ischemic changes in three other patients, confirming the clinical diagnosis. Resection of ischemic bowel can provide relief in patients with segmental intestinal ischemia caused by carcinoid-induced vascular sclerosis.
Nederlands tijdschrift voor geneeskunde, Jan 9, 2005
Bij dysfagie wordt een belemmering gevoeld van de passage van vast of vloeibaar voedsel door de k... more Bij dysfagie wordt een belemmering gevoeld van de passage van vast of vloeibaar voedsel door de keel of slokdarm. Dysfagie, in sommige gevallen samengaand met impactie van een voedselbrok in de slokdarm, komt veel voor en is vaak reden voor endoscopisch onderzoek van het bovenste deel van de tractus digestivus. 1 Bij dysfagie wordt vaak gedacht aan een maligniteit van de slokdarm. Differentiaaldiagnostisch moet er bij passageklachten ook gedacht worden aan motiliteitsstoornissen (bijvoorbeeld door achalasie of sclerodermie), refluxoesofagitis, peptische stenosen, benigne tumoren en compressie van buitenaf. Een aandoening waar vaak niet aan wordt gedacht is eosinofiele oesofagitis. Wij bespreken hier 3 patiënten die wij zagen met deze aandoening.
Nederlands tijdschrift voor geneeskunde, Jan 19, 2005
Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an... more Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complicat...
Nederlands tijdschrift voor geneeskunde, 1997
A 67-year-old man underwent laparotomy for a ruptured aneurysm of the abdominal aorta. Postoperat... more A 67-year-old man underwent laparotomy for a ruptured aneurysm of the abdominal aorta. Postoperatively he was treated with haemodialysis because of perioperatively developed acute renal failure. Hyperkalaemia was temporarily treated with sodium polystyrene sulfonate (Resonium A) after which he lost blood per rectum. A hemicolectomy was necessary because of intractable blood loss due to ulceration of the colon. This complication is related to uraemia and the use of sodium polystyrene sulfonate with or without sorbitol.
The American journal of gastroenterology, 1996
To assess the accuracy of six commonly used diagnostic tests for Helicobacter pylori in a prospec... more To assess the accuracy of six commonly used diagnostic tests for Helicobacter pylori in a prospective study without using any specific test as the gold standard (the patient was regarded as H. pylori-infected if two or more tests, whatever their nature, were positive). In 105 outpatients undergoing upper GI endoscopy, 62 without significant abnormalities, 28 with gastroesophageal reflux disease, 19 with peptic ulcer, one with erosive gastritis, and one with atrophic gastritis (some patients had more than one diagnosis), antral biopsy specimens were taken for culture, polymerase chain reaction, histological examination (hematoxylineosin and Giemsa stains), and rapid urease test. Corpus biopsy specimens were taken for histological examination. Serology (ELISA) and a 13C-urea breath test were also performed. Consistency of diagnosis between two pathologists was assessed by kappa statistics. Sensitivity and specificity, respectively, were as follows: culture, 98.4 and 100%; polymerase c...
Anticancer research
The authors review the result of the selection of patients with a low rectal cancer for pre-opera... more The authors review the result of the selection of patients with a low rectal cancer for pre-operative radiotherapy. The selection was based on the findings of digital examination eventually combined with surgical staging consisting of bimanual palpation during a staging laparotomy or "trial" operation. This selection was used to divide the patients into three groups: one where local radicality could be expected from primary surgery (group 1), one with deeply infiltrating, but mobile tumours requiring 10 x 3 Gy pre-operative radiotherapy (group 2) and one with fixed or borderline resectable tumours requiring protracted pre-operative radiotherapy with 55-59 Gy (group 3). One hundred and one patients were eligible for this study. A resection aiming for pelvic radicality was carried out in 94 patients: primary resection in 38 (group 1), surgery subsequent to 10 x 3 Gy pre-operative radiotherapy in 20 (group 2) and 55-59 Gy in 36 (group 3). The calculated risk of local recurren...
Anticancer research
The aim of this study was to determine the relationship between survival and value of molecular m... more The aim of this study was to determine the relationship between survival and value of molecular markers in the primary tumour in a group of patients with irresectable rectal cancer, treated with preoperative chemo-radiotherapy. Immunohistochemistry for p53, p21, bcl-2 and Ki-67 was performed on pre-treatment biopsy specimens of 34 patients with irresectable rectal cancer. Preoperative treatment consisted of pelvic irradiation of 45-56 Gy, combined with 5FU and leucovorin (350/20 mg/m2 x 5 d; in weeks 1 and 5 during radiotherapy). The median follow-up was 38 months. Endpoints were pathological T-stage and survival after surgery. Expression of p21 correlated significantly with survival (p=0.005). Survival and p21 expression also correlated significantly, when adjusted for tumour response (p=0.005, RR=4.8 (1.6-14.7)). Expression of p21 predicts a worse survival in irresectable rectal cancer treated with preoperative chemo-radiotherapy. No relationship was found between tumour response ...
World journal of gastroenterology : WJG, Jan 7, 2006
Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associate... more Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associated with colorectal and endometrial cancer and a range of other tumor types. Germline mutations in the DNA mismatch repair (MMR) genes, particularly MLH1, MSH2, and MSH6, underlie this disorder. The vast majority of these HNPCC-associated mutations have been proven, or assumed, given the family history of cancer, to be transmitted through several generations. To the best of our knowledge, only a single case of a de novo germline MMR gene mutation (in MSH2) has been reported till now. Here, we report a patient with a de novo mutation in MLH1. We identified a MLH1 Q701X truncating mutation in the blood lymphocytes of a male who had been diagnosed with rectal cancer at the age of 35. His family history of cancer was negative for the first- and second-degree relatives. The mutation could not be detected in the patient' parents and sibling and paternity was confirmed with a set of highly po...
Current pharmaceutical design, Jan 5, 2015
Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling ... more Metastatic rectal cancer patients could benefit from novel therapeutic approaches. The signaling network formed by chemokines and their receptors can promote metastasis and resistance to current anticancer treatments. This study assessed the expression of chemokine receptor 4 (CXCR4) and its ligand CXCL12 immuhistochemically in stage IV rectal tumors. Paraffin-embedded primary tumor collected before and after local radiotherapy and systemic treatment with bevacizumab, oxaliplatin and capecitabine was analyzed. Receptor and ligand expression was assessed in the cytoplasm and nucleus of tumor, stromal and normal rectal crypt cells. Baseline expression of CXCR4 and CXCL12 was correlated with patients' pathologic response to treatment. At diagnosis (n=46), 89% of the rectal tumors expressed cytoplasmic CXCR4 and 81% CXCL12. Nuclear CXCR4 expression in tumor cells was present in 30% and nuclear CXCL12 expression in 35% of the tumors. After radiochemotherapy and bevacizumab, nuclear C...
Hereditary Cancer in Clinical Practice, 2008
H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct t... more H He er re ed di it ta ar ry y C Ca an nc ce er r i in n C Cl li in ni ic ca al l P Pr ra ac ct ti ic ce e 2008; 6(1)
Human Pathology, 2000
A woman is described who developed an ovarian adenocarcinoma, 3 metachronous colorectal adenocarc... more A woman is described who developed an ovarian adenocarcinoma, 3 metachronous colorectal adenocarcinomas, and a primary adrenocortical adenocarcinoma. Genetic investigation of the mismatch repair genes MLH1 and MSH2 showed a germline mutation in MSH2. Colorectal and ovarian carcinoma belong to the tumor spectrum of hereditary nonpolyposis colorectal cancer (HNPCC). Adrenocortical adenocarcinoma, however, has never been described as 1 of the HNPCC-associated tumors. To investigate whether the adrenocortical adenocarcinoma in this patient was caused by the MSH2 germline mutation, determination of microsatellite instability (MSI) and immunohistochemical analysis were performed on 1 of the colorectal tumors and the adrenocortical adenocarcinoma. MSI and gen-eral loss of MSH2 protein expression could be seen in the colorectal tumor but not in the adrenocortical adenocarcinoma. Therefore, it is highly unlikely that the adrenocortical adenocarcinoma found in this patient was due to her genetic predisposition for HNPCC. HUM PATHOL 31:1522-1527.
Digestive and Liver Disease, 2015
Background: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metapl... more Background: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma. Aim: To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma. Methods: Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival. Results: The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P < 0.001) and high-grade dysplasia (82%, P = 0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients (P = 0.599 and P = 0.700 respectively). Conclusion: GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma.