Abstract Background It is unclear whether the increasing incidence of thyroid cancer (TC) due to increased diagnosis of small and indolent tumours might mask a real increase of clinically significant cancers. The aim of this study was to correlate surgery, pathology and outcome data of individual patients to the mode of primary detection (palpation, by imaging or incidental) to assess if TC incidence has increased. Methods The Swedish Cancer Registry identified all patients with TC in Västra Götaland County representing approximately 1.6 million inhabitants. Clinical information was retrieved from medical records of patient cohorts from three study intervals (2001–2002, 2006–2007 and 2011–2014) comprising 60 per cent of all TC patients. Data were also obtained from the NORDCAN registry to compare of TC incidence with other Nordic countries. Results Between 2001 and 2014, the annualized standard incidence rate/100 000 population (ASR) of TC increased from 3.14 to 10.71 in women and from 1.12 to 3.77 in men. This was higher than the mean incidence for Sweden but similar to that in Norway and Finland. Differentiated TC (DTC) increased more than threefold. The majority of tumours (64 per cent) were detected by palpation. Larger tumours (10–20, 21–40 and greater than 40 mm) increased as much as microcarcinomas (less than 10 mm). Only 5 per cent of the tumours were detected by imaging. All disease-specific deaths (8.5 per cent of DTC in the first two cohorts) and most patients with recurrent or persistent disease (6.6 per cent of DTC cases) were diagnosed due to tumour-related symptoms. Conclusion DTC in Western Sweden gradually increased between 2001 and 2014. The majority of tumours were detected by palpation suggesting a real increase in the incidence of clinically significant thyroid malignancies.

Surgery is the only potential cure for patients with medullary thyroid carcinoma (MTC). Preoperative ultrasound, computed tomography and magnetic resonance imaging are not sensitive enough for detection of microscopic disease. The aim of this study was to investigate if routine preoperative 111In-labelled (DTPA-D-Phe1)-octreotide scintigraphy (SRS) could be used as a staging procedure in planning primary surgery in patients with MTC.

Patients with sporadic medullary thyroid carcinoma (MTC) have a variable clinical course. Our aim was to analyse the reduction of tumour markers after thyroidectomy with meticulous dissection and relate it to clinical outcome.

Gastrointestinal stromal tumors (GISTs) are thought to originate from the interstitial cells of Cajal, which share many properties with neurons of the gastrointestinal tract. Recently, we demonstrated expression of the hormone ghrelin in GIST. The aim of the present study was therefore to evaluate a possible neuroendocrine phenotype of GIST. Specimens from 41 GISTs were examined for the expression of 12 different synaptic vesicle proteins. Expression of synaptic-like microvesicle proteins, e.g., Synaptic vesicle protein 2 (SV2), synaptobrevin, synapsin 1, and amphiphysin was demonstrated in a majority of GISTs by immunohistochemistry, western blotting, and quantitative reversetranscriptase PCR. One-third of the tumors also expressed the large dense core vesicle protein vesicular monoamine transporter 1. Presence of microvesicles and dense core vesicles in GIST was confirmed by electron microscopy. The expression of synaptic-like microvesicle proteins in GIST was not related to risk profile or to KIT/platelet derived growth factor alpha (PDGFRA) mutational status. Thus, GISTs regularly express a subset of synaptic-like microvesicle proteins necessary for the regulated secretion of neurotransmitters and hormones. Expression of synaptic-like micro-vesicle proteins, ghrelin and peptide hormone receptors in GIST indicate a neuroendocrine phenotype and suggest novel possibilities to treat therapy-resistant GIST.

A key task for health policymakers is to optimise the outcome of health care interventions. The pricing of a new generation of cancer drugs, in combination with limited health care resources, has highlighted the need for improved methodology to estimate outcomes of different treatment options. Here we introduce new general methodology, which for the first time employs continuous hazard functions for analysis of survival data. Access to continuous hazard functions allows more precise estimations of survival outcomes for different treatment options. We illustrate the methodology by calculating outcomes for adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate, which selectively inhibits the activity of a cancer-causing enzyme and is a hallmark representative for the new generation of cancer drugs. The calculations reveal that optimal drug pricing can generate all win situations that improve drug availability to patients, make the most of public expenditure on drugs and increase pharmaceutical company gross profits. The use of continuous hazard functions for analysis of survival data may reduce uncertainty in health care resource allocation, and the methodology can be used for drug price negotiations and to investigate health care intervention thresholds. Health policy makers, pharmaceutical industry, reimbursement authorities and insurance companies, as well as clinicians and patient organisations, should find the methodology useful.

Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.

Background: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment.Methods: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival.Results: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008).Conclusion: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.

We found the article by Andersson et al1Andersson J. Bumming P. Meis-Kindblom J.M. Sihto H. Nupponen N. Joensuu H. Oden A. Gustavsson B. Kindblom L.G. Nilsson B. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis.Gastroenterology. 2006; 130: 1573-1581Abstract Full Text Full Text PDF Scopus (194) Google Scholar of great interest. They analyzed a series of 233 patients, whose diagnosis of gastrointestinal stromal tumor (GIST) was performed from 1983 through 2000, and found a significant prognostic value of KIT exon 11 deletions. However, we have 2 questions for the authors. First, Andersson et al excluded the 56 oldest cases (24%) of this series for statistical analyses, and we wonder whether they had any scientific and/or technical reasons for this. Indeed, the authors excluded these patients, because of the low frequency of KIT exon 11 mutations. However, the frequency, in this large retrospective series of Swedish patients, was 52% (121/233). It is a bit higher than the mean frequency of 50% for 578 patients reported in the 12 largest retrospective series throughout the world before 2004,2Emile J.F. Theou N. Tabone S. Cortez A. Terrier P. Chaumette M.T. Julie C. Bertheau P. Lavergne-Slove A. Donadieu J. Barrier A. Le Cesne A. Debuire B. Lemoine A. Groupe d’Etude des GISTClinicopathologic, phenotypic, and genotypic characteristics of gastrointestinal mesenchymal tumors.Clin Gastroenterol Hepatol. 2004; 2: 597-605Google Scholar and than that of 47.5% in a more recent study of 162 Spanish patients.3Martin J. Poveda A. Llombart-Bosch A. Ramos R. Lopez-Guerrero J.A. Garcia del Muro J. Maurel J. Calabuig S. Gutierrez A. Gonzalez de Sande J.L. Martinez J. De Juan A. Lainez N. Losa F. Alija V. Escudero P. Casado A. Garcia P. Blanco R. Buesa J.M. Spanish Group for Sarcoma ResearchDeletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS).J Clin Oncol. 2005; 23: 6190-6191Google Scholar It is noteworthy that in the Swedish series, among the different types of KIT exon 11 mutations of the oldest cases, deletions were the only one with a different frequency as compared to the recent cases (10/56 versus 61/177, P < .02). This difference could introduce a bias, and even false the conclusion of this study concerning the poor prognostic value of KIT exon 11 deletions in the whole series. Secondly, correlation of the site of deletion within KIT exon 11 and prognosis of GISTs have been published by several groups.2Emile J.F. Theou N. Tabone S. Cortez A. Terrier P. Chaumette M.T. Julie C. Bertheau P. Lavergne-Slove A. Donadieu J. Barrier A. Le Cesne A. Debuire B. Lemoine A. Groupe d’Etude des GISTClinicopathologic, phenotypic, and genotypic characteristics of gastrointestinal mesenchymal tumors.Clin Gastroenterol Hepatol. 2004; 2: 597-605Google Scholar, 3Martin J. Poveda A. Llombart-Bosch A. Ramos R. Lopez-Guerrero J.A. Garcia del Muro J. Maurel J. Calabuig S. Gutierrez A. Gonzalez de Sande J.L. Martinez J. De Juan A. Lainez N. Losa F. Alija V. Escudero P. Casado A. Garcia P. Blanco R. Buesa J.M. Spanish Group for Sarcoma ResearchDeletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS).J Clin Oncol. 2005; 23: 6190-6191Google Scholar, 4Wardelmann E. Losen I. Hans V. Neidt I. Speidel N. Bierhoff E. Heinicke T. Pietsch T. Buttner R. Merkelbach-Bruse S. Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors.Int J Cancer. 2003; 106: 887-895Google Scholar As Andersson et al, we found no correlation between deletion of Trp557 and/or Lys558 and prognosis. However, we would be grateful, if they could provide data on the survival of patient with other types of KIT exon 11 deletions. Indeed in our previous works,2 we showed that deletions of codons 562-579, in which 2 tyrosines are involved in specific cellular signal transduction pathways, were strongly associated with metastases. Gastrointestinal Stromal Tumors With KIT Exon 11 Deletions Are Associated With Poor PrognosisGastroenterologyVol. 130Issue 6PreviewBackground & Aims: Gain-of-function mutations in the KIT receptor tyrosine kinase gene and rare mutations in the platelet-derived growth factor receptor α (PDGFRA) gene are important events in gastrointestinal stromal tumor (GIST) development. Different mutations are reportedly associated with distinctive phenotypes and possibly clinical behavior. We investigated the correlation among mutation type, phenotype, and clinical course in a preimatinib, population-based series of GIST with long-term follow-up. Full-Text PDF ReplyGastroenterologyVol. 131Issue 3PreviewWe appreciate the interest expressed by Dr. Emile et al regarding the recent article by Andersson et al.1 Full-Text PDF

BACKGROUND & AIMS:Gain-of-function mutations in the KIT receptor tyrosine kinase gene and rare mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene are important events in gastrointestinal stromal tumor (GIST) development. Different mutations are reportedly associated with distinctive phenotypes and possibly clinical behavior. We investigated the correlation among mutation type, phenotype, and clinical course in a preimatinib, population-based series of GIST with long-term follow-up.METHODS:Genomic DNA from 177 GIST patients was analyzed for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 mutations using denaturating high-performance liquid chromatography and bidirectional sequencing.RESULTS:KIT exon 11 mutations were detected in 101 of 177 GIST (61 deletions, 23 missense mutations, and 17 duplications); wild-type (WT) KIT and PDGFRA were detected in 63; KIT exon 9 and exon 17 mutations in 6 and 1, respectively; and PDGFRA exons 12 and 18 mutations in 3 each. GIST >5 cm vs GIST </=1 cm had mutations in 73% and 33%, respectively. KIT exon 11 deletions were significantly associated with a higher proportion of high risk or overtly malignant groups compared with WT GIST. KIT exon 11 deletions adversely affected outcome. KIT exon 11 duplications and exon 9 mutations were found exclusively in gastric and small intestinal GIST, respectively.CONCLUSIONS:KIT exon 11 deletion is an independent adverse prognostic factor in patients with GIST.

There is rapid evolution in the functional imaging of tumours. In two patients with concomitant pheochromocytoma and gastrointestinal stromal tumour (GIST), previously unrecognized tumours were visualized by combined 2-tracer positron emission tomography (PET), which also provided precise information about tumour type. PET imaging led to radical resection and the diagnoses were histopathologically confirmed. GISTs from the Carney patient and the patient with neurofibromatosis type 1 (NF1) both lacked KIT mutations.

BACKGROUND. Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST.METHODS. All patients (n = 1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3-1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk-group stratifications, were analyzed statistically.RESULTS. Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty-four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor-related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor-related deaths occurred in only 2 of 170 of patients (1.2%) with very-low-risk, low-risk, or intermediate-risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high-risk group and the overtly malignant group).CONCLUSIONS. GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk-group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index. (C) 2005 American Cancer Society.

Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings – palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.