Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 109 records · Page 6Linked to original sources

PubMed1998

Micrometastases and survival in stage II colorectal cancer.

BACKGROUND: Standard treatment of colorectal cancer includes adjuvant chemotherapy for patients with stage III disease (defined by the presence of lymph-node metastases), but not for patients with stage II tumors (who have no lymph-node metastases). However, 20 percent of patients with stage II tumors die of recurrent disease. We investigated whether the detection of micrometastases can be used to identify patients with stage II disease who are at high risk for recurrence. METHODS: We analyzed 192 lymph nodes from 26 consecutive patients with stage II colorectal cancer, using a carcinoembryonic antigen-specific nested reverse-transcriptase polymerase chain reaction. Five-year follow-up information was obtained on all patients. Observed and adjusted survival rates were assessed in the patients with and the patients without micrometastases. RESULTS: Micrometastases were detected in one or more lymph nodes from 14 of 26 patients (54 percent). The adjusted five-year survival rate (for which only cancer-related deaths were considered) was 50 percent in this group, whereas in the 12 patients without micrometastases, the survival rate was 91 percent (P=0.02 by the log-rank test). The observed five-year survival rates were 36 percent and 75 percent, respectively (P=0.03). The groups were similar with respect to age, sex, tumor side (location in relation to the flexura lienalis), degree of tumor differentiation (grade), and diameter of the primary tumor. CONCLUSIONS: Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer.

Aged↗

PubMed1998

The prognostic significance of p53 expression for survival and local control in rectal carcinoma treated with surgery and postoperative radiotherapy.

PURPOSE: To investigate whether p53 immunoreactivity is a prognostic factor for survival and pelvic control in rectal carcinoma treated with surgery and postoperative radiotherapy. METHODS AND MATERIALS: From 1981 through 1989, 146 patients with rectal carcinoma received postoperative radiotherapy and were followed for at least 5 years or until death. The specimens of 123 of these 146 patients could be retrieved and examined immunohistochemically for p53 expression. The prognostic value for survival and pelvic control of p53 expression and other patient and treatment factors was examined by univariate and multivariate analyses. RESULTS: p53 expression has no prognostic significance for overall survival in this group of 123 patients. The only prognostic factor for survival in this material is tumor stage (p < 0.01). The actuarial pelvic recurrence rates of p53- and p53+ cases are different in favor of the p53- ones. In the univariate analysis this difference is significant (p = 0.05). However, in the multivariate analysis the influence of p53 expression, additional to stage, becomes nonsignificant (p = 0.10). This indicates that p53 expression is not a strong independent prognostic factor for pelvic recurrence. In the multivariate analysis stage turns out to be the only predictor of pelvic recurrence (p = 0.03). When only recurrences inside the radiation field are considered, there is no difference between p53+ and p53-cases. CONCLUSION: Based on this material, we have found no convincing evidence that p53 expression is an important predictor of survival or local control in rectal cancer treated with surgery and postoperative radiotherapy. We have found no evidence that possible differences in radiosensitivity between p53+ and p53- tumors have clinical significance for this group of patients.

Adenocarcinoma↗

PubMed1998

The value of ultrasound with ultrasound-guided fine-needle aspiration biopsy compared to computed tomography in the detection of regional metastases in the clinically negative neck.

PURPOSE: Head and neck oncologists have not reached consensus regarding the role of contemporary imaging techniques in the evaluation of the clinically negative neck in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to compare the accuracy of ultrasound with guided fine-needle aspiration biopsy (UGFNAB) and computed tomography (CT) in detecting lymph node metastasis in the clinically negative neck. METHODS AND MATERIALS: Sixty-four neck sides of patients with HNSCC were examined preoperatively by ultrasound/UGFNAB and CT at one of five participating tertiary care medical centers. The findings were correlated with the results of histopathologic examination of the neck specimen. RESULTS: Ultrasound with guided fine-needle aspiration biopsy was characterized by a sensitivity of 48%, specificity of 100%, and overall accuracy of 79%. Three cases had nondiagnostic aspirations using UGFNAB and were excluded. CT demonstrated a sensitivity of 54%, specificity of 92%, and overall accuracy of 77%. UGFNAB detected two additional metastases not visualized on CT, whereas CT detected no metastases not seen on UGFNAB. The results of UGFNAB were similar between the participating centers. CONCLUSIONS: Approximately one half of the clinically occult nodal metastases in our patient group were identified by both CT and UGFNAB. Overall, UGFNAB and CT demonstrated comparable accuracy. The sensitivity of CT was slightly better than UGFNAB, but the latter remained characterized by a superior specificity. The results of CT and UGFNAB did not appear to be supplementary. The choice of imaging modality for staging of the clinically negative neck depends on tumor site, T-stage, and experience and preference of the head and neck oncologist. If CT is required for staging of the primary tumor, additional staging of the neck by UGFNAB does not provide significant additional value.

Biopsy, Needle↗

PubMed1998

Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival.

PURPOSE: To study risk factors for local recurrence (LR) after breast-conserving therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode of detection, location, treatment, influence of radiation therapy, and impact on survival. METHODS AND MATERIALS: 1360 patients (median age 52 years; range 24-88) with a total of 1393 pT1-2 N0-1 tumors treated with BCT between 1980-1994 were studied (median follow-up 52 months). The adequacy of radiation treatment of the patients developing LR was studied in a quality control study. The impact of LR on overall survival and distant metastasis was studied in a Cox regression model with LR as a time-dependent covariate. RESULTS: A total of 88 LR occurred with a 5- and 10-year LR risk of 8 and 12%. Age was the only significant risk factor. Compared to patients > 65 years old, patients < 45 years old and patients 45-65 years old had a relative risk (RR) of 4.09 and 2.41, respectively, of developing LR. Risk on LR was found to increase gradually with younger age. Radiation therapy was considered adequate and did not play a role in influencing the LR rate. Almost 65% of the LR were true or marginal recurrences. Of all LR, 80% appeared during the first 5 years and were detected with equal frequency by the patient herself, the physician, and annual mammography. LR was a major predictor for distant metastasis (RR: 4.90; 3.15-7.62) and death (RR: 4.29; 2.93-6.28). CONCLUSION: Young age is a major risk factor for LR and there is a significant gradual increase in LR with decreasing age. LR is associated with a higher risk of distant metastasis and death. Whether LR is the cause of or a marker for distant metastasis remains unresolved.

Adult↗

PubMed1998

[Risk factors for the development of phlebitis in peripheral infusions].

OBJECTIVE: To study the incidence and risk factors of development of phlebitis caused by peripheral infusions. DESIGN: Prospective, descriptive. SETTING: Westindies Hospital, The Hague, the Netherlands. METHODS: For all 348 patients given infusions in a 6-week period the development of phlebitis, if any, and the contributing factors were studied. RESULTS: Phlebitis developed in 136 patients (39%), after an average of 2.9 days (range: 1-14). Risk factors were female sex, earlier phlebitis, insertion on the ventral surface of the forearm and administration of antibiotics via the infusion. These factors were not interdependent. No correlation was found between development of phlebitis and the size of the needle. CONCLUSION: Development of phlebitis depends on a number of factors. Timely removal of the infusion can prevent the development of phlebitis. Infusions should preferably be administered via the hand.

Adolescent↗

PubMed1998

Beneficial effects of leukocyte depletion of transfused blood on postoperative complications in patients undergoing cardiac surgery: a randomized clinical trial.

BACKGROUND: Leukocytes in transfused blood are associated with several posttransfusion immunomodulatory effects. Although leukocytes play an important role in reperfusion injury, the contribution of leukocytes in transfused blood products has not been investigated. To estimate the role and the timing of leukocyte filtration of red cells in cardiac surgery, we performed a randomized study. METHODS AND RESULTS: Patients scheduled for cardiac surgery were randomly allocated to receive either packed cells without buffy coat (PC, n = 306), fresh-filtered units (FF, n = 305), or stored-filtered units (SF, n = 303) when transfusion was indicated. We evaluated the periods of hospitalization and stay at the intensive care unit, and the occurrences of postoperative complications up to 60 days after surgery. The average hospital stay was 10.7 days, of which 3.2 days were in the intensive care unit, without significant differences between the groups. In the PC trial arm, 23.0% of the patients had infections versus 16.9% and 17.9% of the patients in the leukocyte-depleted trial arms (P=.13). Within 60 days, 45 patients had died, 24 patients in the PC trial arm (7.8%), versus 11 (3.6%) and 10 (3.3%) patients in the FF and SF trial arms, respectively (P=.015). CONCLUSIONS: In cardiac surgery patients, especially when more than three blood transfusions are required, leukocyte depletion by filtration results in a significant reduction of the postoperative mortality that can only partially be explained by the higher incidence of postoperative infections in the PC group.

Aged↗

PubMed1998

Morbidity and mortality of reconstructive surgery of noninfected false aneurysms detected long after aortic prosthetic reconstruction.

OBJECTIVE: To determine the morbidity and mortality of surgical treatment of false (anastomotic) aneurysms, we analyzed the results of 158 consecutive surgical procedures for repair of false aneurysms that were detected as a result of a surveillance program after aortic reconstruction with a prosthesis. DESIGN: Retrospective analysis of patient data from a vascular registry that included information on the long-term follow-up of our patients. SETTING: A university hospital (tertiary referral center) in the Netherlands that has been performing vascular reconstructive surgery since 1958. PATIENTS: We performed 158 surgical procedures on 135 patients with 220 noninfected false aneurysms. Using a yearly surveillance program, the false aneurysms were detected at a mean interval of 8 years after the initial reconstruction. Most patients (60%) were asymptomatic. The operation was performed as an emergency in 25 instances (16%). RESULTS: The mortality rate of patients receiving nonsurgical treatment was very high (61%) owing to documented rupture (11 of 18 patients). The intraoperative death rate was 7.6% per procedure. This was higher for emergency (24%) than for elective procedures (4.5%). CONCLUSIONS: Conservative follow-up carries a very high mortality rate, as does emergency surgery for a false aneurysm. However, the intraoperative mortality rate of elective reconstruction of a false aneurysm can be in the same range as that of elective primary aortic reconstruction. Therefore, we advocate a surveillance program, including yearly ultrasound studies, after prosthetic aortic reconstruction for the timely detection and elective repair of all false aneurysms.

Adult↗

PubMed1998

Subtle involuntary movements are not reliable indicators of incipient Huntington's disease.

In the past, Huntington's disease was diagnosed when movement disturbances were present in concordance with a positive family history. Early motor signs, however, are often not found in a standard neurologic examination, and their expression is variable. Not until later stages of the disease could one be sure about the diagnosis. Since genetic diagnosis became available, the onset of symptoms and signs could be studied in the earliest phase. The aim of the study was to evaluate observer agreement of the assessment of early motor signs in Huntington's disease. A total of 17 gene carriers, 22 noncarriers, and eight partners were recorded on video performing several facial movements after instruction and engaging in a 5-minute conversation. Three experienced neurologists, unaware of the genetic status of the participants, judged and classified the video recordings independently. The cases with disagreement were judged a second time after the neurologists discussed these cases. The observer agreement after the first judgment is poor (kappas 0.09, 0.24, 0.45) and after the second judgment satisfactory (kappas 0.79, 0.90, 0.78). Consequences for clinical practice and research programs into early symptoms and signs are discussed.

Adult↗

PubMed1998

Does CSF outflow resistance predict the response to shunting in patients with normal pressure hydrocephalus?

The value of the measurements of CSF outflow resistance (Rcsf) relative to predicting outcome after shunting was studied. In a group of 101 patients with mainly idiopathic normal pressure hydrocephalus (NPH) Rcsf was obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified using an NPH scale (NPHS) and disability by the Modified Rankin scale (MRS). Patients were assessed before and at 1, 3, 6, 9 and 12 months after surgery. Outcome measures were differences between the preoperative and last NPHS and MRS scores. Improvement was defined as a change of > or = 15% in NPHS and > or = 1 grade in MRS. Intention-to-treat analysis of all patients at one year yielded improvement of 57% in NPHS and 59% in MRS. Efficacy analysis, excluding comorbidity unrelated to NPH, revealed positive predictive values of around 80% at Rcsf < 18, and between 90% and 100% at Rcsf > or = 18 mm Hg/ml/min. For Rcsf > or = 18, the likelihood ratios were also higher. We conclude that the best predictor of the response to shunting is an Rcsf > or = 18 mm Hg/ml/min. Since two-thirds of the patients with Rcsf < 18 showed improvement as well, these patients should not be denied shunting.

Cerebrospinal Fluid Pressure↗

PubMed1998

Long-term graft survival after liver transplantation in the UW era: late effects of cold ischemia and primary dysfunction. European Multicentre Study Group.

The use of University of Wisconsin (UW) solution in liver transplantation (LTX) has significantly prolonged preservation times and facilitated semielective transplant procedures. Despite this advantage potential risk factors related to the donor, recipient, or cold storage method will persist in the UW era and detrimental effects will be reflected by primary dysfunction (PDF) after LTX. Concern has been voiced about the maximum period of UW preservation in LTX and various cold ischemia times (CIT) are mentioned. To evaluate the effect of UW solution in LTX, a prospective European multicenter study was initiated in 1988 and short-term results have been reported previously. This report focuses on the long-term effects and survival of prolonged preservation with UW solution and primary function after LTX. Three hundred and fifteen LTXs were performed in 288 patients in participating European centers. Complete follow up of at least 6 years was available for 296 grafts in 277 patients. Effects of donor, preservation, and recipient risk factors on PDF including primary non-function (PNF) and initial poor function (IPF) were evaluated. Next, the effect of risk factors on graft survival (GS) was analyzed including the long-term impact of PNF and IPF using multivariate analyses and the Kaplan-Meyer method. PDF occurred in 15.2% (45/296) with PNF in 7.8% and IPF in 7.4%. Patients with IPF had a 34% lower GS at 3 months those with immediate function (IF; 58% vs 91%; P < 0.001). This difference persisted up to 6 years for patients with IPF with a 39% GS vs 72% after IF (P < 0.001). Median CIT was significantly longer in grafts with PNF compared to IPF or IF (P = 0.03). Long-term GS, however, was significantly influenced at a lower CIT threshold with a 6-year GS for CIT < or = 16 h of 67%, compared to a CIT > 16 h of 51% (P = 0.02). Other independent risk factors for the 6-year survival rate were re-LTX, ABO incompatibility, and recipient diagnosis of acute hepatic failure. In conclusion, liver patients with PNF, but not with IPF, have a significantly lower CIT. IPF is associated with a significantly lower 3 month GS compared to IF, but this difference of 34% does not further increase during a 6-year follow up. Although a short term follow up (3 months) shows that with UW solution CIT up to 18 h has no adverse effect on GS, the 6-year data clearyl suggest that CIT should be kept to less than < 16 h to avoid tetrimental effects on lang-term GS after LTX.

Adenosine↗

PubMed1998

MR imaging of hyaline cartilage at 0.5 T: a quantitative and qualitative in vitro evaluation of three types of sequences.

OBJECTIVE: To identify an optimal pulse sequence for in vitro imaging of hyaline cartilage at 0.5 T. MATERIALS AND METHODS: Twelve holes of varying diameter and depth were drilled in the cartilage of two pig knees. These were submerged in saline and scanned with a 0.5-T MR system. Sixteen T1-weighted gradient echo (GE), two T2-weighted GE, and 16 fast spin echo sequences were used, by varying repetition time (TR), echo time (TE), flip angle (FA), echo train length, profile order, and by use of fat saturation. Contrast-to-noise ratios (CNR) of cartilage versus saline solution and cartilage versus subchondral bone were measured. Cartilaginous lesions were evaluated separately by three independent observers. Interobserver variability and correlation between the quantitative and qualitative analyses were calculated. RESULTS: The mean CNRs of two specimens of cartilage versus saline solution ranged from 6.3 (+/- 2.1) to 27.7 (+/- 2.5), and those of cartilage versus subchondral bone from 0.3 (+/- 0.2) to 22.5 (+/- 1.4). The highest CNR was obtained with a T1-weighted spoiled 3D-GE technique (TR 65 ms, TE 11.5 ms, FA 45 degrees). The number of lesions observed per sequence varied from 35 to 69. Observer agreement was fair to good. The T1-weighted spoiled GE sequences with a TR of 65 ms, TE of 11.5 ms and FA of 30 degrees and 45 degrees were significantly superior to the other 34 sequences in the qualitative analysis. CONCLUSION: T1-weighted spoiled 3D-GE sequences with a TR of 65 ms, a TE of 11.5 ms, and a FA of 30-45 degrees were found to be optimal for in vitro imaging of cartilage at 0.5T.

Animals↗

PubMed1998

Can helical CT replace scintigraphy in the diagnostic process in suspected pulmonary embolism? A retrolective-prolective cohort study focusing on total diagnostic yield.

The aim of our study was to compare the diagnostic value of helical CT vs that of ventilation-perfusion (V/Q) scintigraphy as a first-line test in a diagnostic strategy in patients suspected of pulmonary embolism (PE). In a retrolective-prolective cohort study we tested the accuracy of helical CT vs V/Q scintigraphy in 123 patients suspected of PE. A diagnostic panel was asked to formulate the presumptive diagnosis on the presence or absence of PE, or of alternative disease by using two competing diagnostic strategies. These consisted of the patient history, laboratory tests and chest X-ray (together baseline tests) in combination with either helical CT or V/Q scintigraphy (CT strategy and V/Q strategy, respectively). The results were compared with the final diagnosis in each patient that was established from various reference tests (which included V/Q scintigraphy, pulmonary angiography and clinical follow-up). The CT and V/Q strategies were compared with regard to the accuracy for PE, for alternative diseases and with regard to the proportion of conclusive diagnoses that were made. The CT strategy was more accurate than the V/Q strategy for detecting or excluding PE. Sensitivity and specificity were 49 and 74 % for the V/Q strategy and 75 and 90 % for the CT strategy, respectively (P = 0.01). The CT strategy provided a conclusive diagnosis in a significantly larger proportion of patients than the V/Q strategy, 92 vs 72 % (P < 0.001). The CT strategy detected more alternative diagnosis than the V/Q strategy, 93 vs 51 %, respectively (P < 0.001). Helical CT seems more useful than V/Q scintigraphy as a first-line test in patients suspected of PE.

Adult↗

PubMed1998

Pressure sores and tube feeding in patients with a fracture of the hip: a randomized clinical trial.

Pressure sores are a frequent problem, especially in elderly patients. Nutritional status may influence the incidence, progression and severity of pressure sores, data, however, are contradictory (1). The purpose of this study was to determine the effect of supplemental feeding on the nutritional status and the development and severity of pressure sores. The effect of supplemental feeding overnight (tube +) on patients with a fracture of the hip and a high pressure-sore risk score, was studied in a randomized clinical trial. The control group (tube -) had no supplemental feeding. After informed consent, 140 patients were randomized, and 129 of these took part in the trial (62 tube +, and 67 tube -). Protein and energy intake, haemoglobin, serum albumin, total serum protein and pressure-sore grade were measured at admission and after 1 and 2 weeks. Of the 62 patients randomized for tube feeding (tube +), only 25 tolerated their tube for more than 1 week and 16 for 2 weeks. Nevertheless, energy and protein intake was significantly higher in the tube + group (P < 0.001). This, however, did not significantly influence total serum protein, serum albumin and development and severity of pressure sores after 1 and 2 weeks. Comparison of the actually tube fed group (n=25 at 1 week, n = 16 at 2 weeks) and the control group showed a 2-3 times higher protein and energy intake (P < 0.0001), and a significantly higher total serum protein and serum albumin after 1 and 2 weeks in the actually tube fed group (all P < 0.001). Pressure-sore development and severity were not significantly influenced in the actually tube fed group. We conclude that we were not able to show a significant decrease in development and severity of pressure sores, because the nasogastric tube for supplemental feeding was not well tolerated in this patient group. Nevertheless, tube feeding overnight does result in a significant higher protein and energy intake, and has a significant effect on nutritional status in the actually tube-fed group. Other means of supplemental feeding will have to be used in order to answer the question of whether supplemental feeding can decrease development and severity of pressure sores.

Aged↗

PubMed1998

Duodenal meal stimulation leads to coeliac artery vasoconstriction and superior mesenteric artery vasodilatation: an intra-abdominal ultrasound study.

To evaluate the influence of duodenal feeding on splanchnic blood flow, 14 patients with normal coeliac and superior mesenteric arteries underwent intra-abdominal duplex scanning of the systemic and splanchnic circulation under standardised basal and meal-stimulated conditions. Doppler samples and diameter measurements were taken of the aorta, coeliac artery, common hepatic artery, splenic artery, superior mesenteric artery, and inferior mesenteric artery. Duodenal meal stimulation has no systemic effects (p > 0.4). However, duodenal meal stimulation results in coeliac artery vasoconstriction (p < 0.06) and superior mesenteric artery vasodilatation (p < 0.05). This study supports other reported results that gastrointestinal blood flow is dependent on the site of food stimulation.

Aged↗

PubMed1998

Elderly patients with non-Hodgkin's lymphoma: population-based results in The Netherlands.

BACKGROUND: To compare characteristics, treatment and outcome of patients > or = 70 years with patients < 70 years in a population-based non-Hodgkin's lymphoma (NHL) registry. PATIENTS AND METHODS: All new patients with NHL (n = 1168) in a geographically defined region in the western part of The Netherlands were registered during a nearly 10-year period. Patient, tumour and treatment characteristics, response to therapy and survival were analysed for both age groups. An age-adjusted prognostic index was determined for elderly patients with aggressive lymphoma. RESULTS: The elderly comprised 41% of the registered patients. There were significantly more females, a preponderance of intermediate-grade histology (diffuse large B-cell lymphoma) and a lower performance status. Incomplete staging in the elderly was mostly due to the omission of a bone marrow biopsy. With respect to WF grading the complete remission rate (except for patients with low-grade/stage I NHL, patients with extranodal NHL and for patients with intermediate grade/extensive NHL) and overall survival at five years (except for patients with low-grade/stage I NHL and for patients with intermediate-grade/extensive NHL) were significantly inferior in the elderly. With respect to the R.E.A.L. Classification the exceptions were in patients with high grade MALT lymphomas (elderly good) and patients with mantle-cell and peripheral T-cell lymphomas (younger group bad too). However, once complete remission was reached, the disease-free survival did not differ significantly between the two age groups, emphasising the importance of achieving complete remission. Although 65% of the classified elderly patients presented with intermediate-grade NHL, only 26% of the elderly patients treated with chemotherapy received anthracycline-based chemotherapy. In the elderly, lymphoma (treatment-related toxicity included) contributed to death in 70% and concomitant disease (other malignancy included) in 30%, versus 78% and 22%, respectively, for the younger group (P = 0.04). The age-adjusted prognostic index, made up of the factors serum LDH, stage and Karnofsky index, showed a clear distinction between the four risk categories low, low/intermediate, intermediate/high and high, with a median survival time of 43, 20, seven and four months, respectively. For the younger group the respective numbers were 144, 45, 19 and 11 months. CONCLUSIONS: In a population-based NHL registry the elderly, predominately female patients, formed a larger proportion of the patient group than the one usually reported in the literature. In this population-based cohort inferior remission and overall survival rates were seen in the elderly. However, obtaining complete remission was beneficial for the prognosis of this disease in the elderly. By the application of the R.E.A.L. Classification important subgroups emerge.

Aged↗

PubMed1998

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance.

To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2.

Adolescent↗

PubMed1998

Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix.

Loss of heterozygosity (LOH) frequently occurs in squamous cell carcinomas of the uterine cervix and indicates the probable sites of tumour-suppressor genes that play a role in the development of this tumour. To define the localization of these tumour-suppressor genes, we studied loss of heterozygosity in 64 invasive cervical carcinomas (stage IB and IIA) using the polymerase chain reaction with 24 primers for polymorphic repeats of known chromosomal localization. Chromosomes 3, 11, 13, 16 and 17, in particular, were studied. LOH was frequently found on chromosome 11, in particular at 11q22 (46%) and 11q23.3 (43%). LOH on chromosome 11p was not frequent. On chromosome 17p13.3, a marker (D17S513) distal to p53 showed 38% LOH, whereas p53 itself showed only 20% LOH. On the short arm of chromosome 3, LOH was frequently found (41%) at 3p21.1. The beta-catenin gene is located in this chromosomal region. Therefore, expression of beta-catenin protein was studied in 39 cases using immunohistochemistry. Staining of beta-catenin at the plasma membrane of tumour cells was present in 38 cases and completely absent in only one case. The tumour-suppressor gene on chromosome 3p21.1 may be beta-catenin in this one case, but (an)other tumour-suppressor gene(s) must also be present in this region. For the other chromosomes studied, 13q (BRCA-2) and 16q (E-cadherin), only sporadic losses (< 15% of cases) were found. Expression of E-cadherin was found in all of 37 cases but in six cases the staining was very weak. No correlation was found between clinical and histological parameters and losses on chromosome 3p, 11q and 17p. In addition to LOH, microsatellite instability was found in one tumour for almost all loci and in eight tumours for one to three loci. In conclusion, we have identified three loci with frequent LOH, which may harbour new tumour-suppressor genes, and found microsatellite instability in 14% of cervical carcinomas.

Adenocarcinoma↗

PubMed1998

Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Allogeneic bone marrow transplantation (BMT) offers a potential cure for younger patients with myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia (sAML). More than 600 patients from 50 European centers have now been reported to the European Group for Blood and Marrow Transplantation (EBMT). We retrospectively analyzed 131 patients reported to the Chronic Leukemia Working Party of the EBMT who underwent BMT from HLA-identical siblings without prior remission induction chemotherapy. At the time of BMT 46 patients had refractory anemia (RA) or RA with ringed sideroblasts, 67 patients had more advanced MDS subtypes and 18 patients had progressed to sAML. The 5-year disease-free (DFS) and overall survival (OS) for the entire group of patients was 34 and 41%, respectively. Fifty patients died from transplant-related complications, most commonly graft-versus-host disease and/or infections. Relapse occurred in 28 patients between 1 and 33 months after BMT, resulting in an actuarial probability of relapse of 39% at 5 years. DFS and OS were dependent on pretransplant bone marrow blast counts. Patients with RA/RARS, RAEB, RAEB/T and sAML had a 5-year DFS of 52, 34, 19 and 26%, respectively. The 5-year OS for the respective patient groups was 57, 42, 24 and 28%. In a multivariate analysis, younger age, shorter disease duration, and absence of excess of blasts were associated with improved outcome. From these data we conclude that patients with myelodysplasia who have appropriate marrow donors, especially those aged less than 40 years and those with low medullary blast cell count should be treated with BMT as the primary treatment early in the course of their disease. Transplantation early after establishing the diagnosis of MDS may improve prognosis due to a lower treatment-related mortality and a lower relapse risk.

Adolescent↗