54 research outputs found
Variable clinical expression in patients with a germline MEN1 disease gene mutation: clues to a genotype–phenotype correlation
Multiple endocrine neoplasia type 1 is an inherited endocrine tumor syndrome, predominantly characterized by tumors of the parathyroid glands, gastroenteropancreatic tumors, pituitary adenomas, adrenal adenomas, and neuroendocrine tumors of the thymus, lungs or stomach. Multiple endocrine neoplasia type 1 is caused by germline mutations of the multiple endocrine neoplasia type 1 tumor suppressor gene. The initial germline mutation, loss of the wild-type allele, and modifying genetic and possibly epigenetic and environmental events eventually result in multiple endocrine neoplasia type 1 tumors. Our understanding of the function of the multiple endocrine neoplasia type 1 gene product, menin, has increased significantly over the years. However, to date, no clear genotype–phenotype correlation has been established
Living with a Hereditary Form of Cancer: Experiences and Needs of MEN 2 Patients and Their Families
Unlike the purely medical research done in multiple endocrine neoplasia type 2 (MEN 2) families, little work has been done on the psychosocial aspects of the disease. To assess the severely stressful influences and the consequences of that stress on the family network, a small-scale survey was carried out during a national meeting. The goal of the study was to obtain more information about the experiences and needs of MEN 2 patients and their relatives. Of the 59 respondents, 85% were satisfied with the medical information provided, 81% were satisfied with the medical knowledge of the specialist, but only 12% were satisfied with the medical knowledge of the general practitioner regarding MEN 2. Furthermore, 63% of the parents had difficulties in talking about the disease with their children. The need expressed for contact with fellow sufferers and their families is expected to lead to the establishment of an interest group for MEN 2 families
Radioiodine treatment of hyperthyroidism: fixed or calculated doses; intelligent design or science?
Evolutionary Pathways of the Calcitonin (CALC) Genes
Recombinant DNA techniques have made it possible to establish the structure of various genes encoding polypeptide hormones. Comparison of nucleotide sequences of the calcitonin (CALC) genes in man has revealed surprising similarities and variations. These findings and the homologies among the sequences in different species offered an opportunity for speculation about relationships between these genes and about their evolutionary origin. The first gene (CALC-I) directing the synthesis of calcitonin (CT) or CT gene-related peptide (CGRP) comprises six exons and gives rise to two mRNAs by an alternative RNA-processing mechanism. The homology between CGRP and CT reflects their common origin. The human genome contains a second gene (CALC-II) that is structurally related to the CALC-I gene. The CALC-II RNA transcripts do not appear to be differentially processed, as only preproCGRP-II mRNA and not preproCT-II is detected. The first and second CTI CGRP genes probably have evolved from a common ancestor gene early in evolution. Meanwhile, a third genomic locus containing nucleotide sequences highly homologous to exons 2 and 3 of both CALC genes was detected and probably generated by duplication of a part of CALC-II. This locus is not likely to encode a CT- or CGRP-related polypeptide hormone. The CALC genes and this last (pseudo) gene are located on the short arm of chromosome 11. Recently, islet or insulinoma-amyloid polypeptide (IAPP) was isolated as a major constituent of amyloid present in human insulinoma and in pancreatic islet amyloid in noninsulin-dependent diabetes mellitus. lAPP shows 46% amino acid sequence homology with human CGRP-II. In contrast to the CALC-genes, the human IAPP gene is located on chromosome 12. All these findings have provided insight into the mechanisms underlying the increasing diversity of polypeptide hormones
Short-term postoperative outcomes after liver resection in the elderly patient:a nationwide population-based study
BACKGROUND: Liver resection is high-risk surgery in particular in elderly patients. The aim of this study was to explore postoperative outcomes after liver resection in elderly patients. METHODS: In this nationwide study, all patients who underwent liver resection for primary and secondary liver tumours in the Netherlands between 2014 and 2019 were included. Age groups were composed as younger than 70 (70-), between 70 and 80 (septuagenarians), and 80 years or older (octogenarians). Proportion of liver resections per age group and 30-day major morbidity and 30-day mortality were assessed. RESULTS: In total, 6587 patients were included of whom 4023 (58.9%) were younger than 70, 2135 (32.4%) were septuagenarians and 429 (6.5%) were octogenarians. The proportion of septuagenarians increased during the study period (aOR:1.06, CI:1.02-1.09, p < 0.001). Thirty-day major morbidity was higher in septuagenarians (11%) and octogenarians (12%) compared to younger patients (9%, p = 0.049). Thirty-day mortality was higher in septuagenarians (4%) and octogenarians (4%) compared to younger patients (2%, p < 0.001). Cardiopulmonary complications occurred more frequently with higher age, liver-specific complications did not. Higher age was associated with higher 30-day morbidity and 30-day mortality in multivariable logistic regression. CONCLUSION: Thirty-day major morbidity and 30-day mortality are higher after liver resection in elderly patients, attributed mainly to non-surgical cardiopulmonary complications
Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes
Introduction: Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. Materials and methods: All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. Results: In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found. Conclusion: Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found
Case-mix adjustment to compare nationwide hospital performances after resection of colorectal liver metastases
Background: Differences in patient demographics and disease burden can influence comparison of hospital performances. This study aimed to provide a case-mix model to compare short-term postoperative outcomes for patients undergoing liver resection for colorectal liver metastases (CRLM). Methods: This retrospective, population-based study included all patients who underwent liver resection for CRLM between 2014 and 2018 in the Netherlands. Variation in case-mix variables between hospitals and influence on postoperative outcomes was assessed using multivariable logistic regression. Primary outcomes were 30-day major morbidity and 30-day mortality. Validation of results was performed on the data from 2019. Results: In total, 4639 patients were included in 28 hospitals. Major morbidity was 6.2% and mortality was 1.4%. Uncorrected major morbidity ranged from 3.3% to 13.7% and mortality ranged from 0.0% to 5.0%. between hospitals. Significant differences between hospitals were observed for age higher than 80 (0.0%-17.1%, p <0.001), ASA 3 or higher (3.3%-36.3%, p <0.001), histopathological parenchymal liver disease (0.0%-47.1%, p <0.001), history of liver resection (8.1%-36.3%, p <0.001), major liver resection (6.7%-38.0%, p <0.001) and synchronous metastases (35.5%-62.1%, p <0.001). Expected 30-day major morbidity between hospitals ranged from 6.4% to 11.9% and expected 30-day mortality ranged from 0.6% to 2.9%. After case-mix correction no significant outliers concerning major morbidity and mortality remained. Validation on patients who underwent liver resection for CRLM in 2019 affirmed these outcomes. Conclusion: Case-mix adjustment is a prerequisite to allow for institutional comparison of short-term postoperative outcomes after liver resection for CRLM. (C) 2020 University Medical Center Groningen. Published by Elsevier Ltd
A patient with bilateral pheochromocytoma as part of a Von Hippel-Lindau (VHL) syndrome type 2C
Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis
<p>Abstract</p> <p>Background</p> <p>Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes.</p> <p>Methods</p> <p>We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of <it>EFNA1 </it>in cases with 1q gain, and <it>EFNA1 </it>expression was correlated with the expression of a target gene (<it>VEGF</it>). The <it>BOP1 </it>gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. <it>SMAD2 </it>was the most down-regulated gene on 18q, and on 20q, <it>STMN3 </it>and <it>TGIF2 </it>were highly up-regulated. Immunohistochemistry for SMAD4 correlated with <it>SMAD2 </it>gene expression and 18q loss.</p> <p>Conclusion</p> <p>On basis of integrative analysis this study identified one well known CRC gene (<it>SMAD2</it>) and several other genes (<it>EFNA1, BOP1, TGIF2 </it>and <it>STMN3</it>) that possibly could be used for rectal cancer characterization.</p
Nationwide oncological networks for resection of colorectal liver metastases in the Netherlands:Differences and postoperative outcomes
INTRODUCTION: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. METHODS: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. RESULTS: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. CONCLUSION: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued
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