Immunohistochemical Glucagon-like Peptide-1 Receptor Expression in Human Insulinomas.

Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1-5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients.

Immunohistochemical somatostatin receptor expression in insulinomas.

Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1-5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome. This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1-5 antibodies. All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%) and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, p = 0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106-11,277), p = 0.033, and HR 6.805 (95% CI 1.364-33.955), p = 0.019 respectively]. Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival.

The impact of interprofessional education on students' current and desired competence in diabetes care.

AIM: To explore the impact of interprofessional education (IPE) on undergraduate nursing and medical students' knowledge, competence and targeted competence in diabetes care. DESIGN: Mixed methods design. METHODS: A voluntary IPE course of diabetes management was organized for nursing (n = 15) and medical (n = 15) students, who performed a diabetes knowledge test and self-evaluation of diabetes competence before and after the course and were compared with non-participating students. The participating students' focus-group interviews were analysed using inductive content analysis. RESULTS: The IPE course improved nursing students' diabetes knowledge and self-evaluated competence among nursing and medical students. The baseline differences in self-evaluated competence between the groups disappeared. The non-participating students evaluated their competence higher than the participants, though they scored lower or equally in the knowledge test. In conclusion, IPE showed potential in increasing students' self-evaluated competence, motivation to learn more and nursing students' diabetes knowledge, offering better prospects for future interprofessional diabetes management.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Characteristics and Outcomes of 79 Patients with an Insulinoma: A Nationwide Retrospective Study in Finland.

OBJECTIVE: Insulinomas are rare pancreatic tumours. Population-based data on their incidence, clinical picture, diagnosis, and treatment are almost nonexistent. The aim of this study was to clarify these aspects in a nationwide cohort of insulinoma patients diagnosed during three decades. DESIGN AND METHODS: Retrospective analysis on all adult patients diagnosed with insulinoma in Finland during 1980-2010. RESULTS: Seventy-nine patients were diagnosed with insulinoma over the research period. The median follow-up from diagnosis to last control visit was one (min 0, max 31) year. The incidence increased from 0.5/million/year in the 1980s to 0.9/million/year in the 2000s (p = 0.002). The median diagnostic delay was 13 months and did not change over the study period. The mean age at diagnosis was 52 (SD 16) years. The overall imaging sensitivity improved from 39% in the 1980s to 98% in the 2000s (p < 0.001). Seventy-one (90%) of the patients underwent surgery with a curative aim, two (3%) had palliative surgery, and 6 (8%) were inoperable. There were no significant differences in the types of surgical procedures between the 1980s, 1990s, and 2000s; tumour enucleations comprised 43% of the operations, distal pancreatic resections 45%, and pancreaticoduodenectomies 12%, over the whole study period. Of the patients who underwent surgery with a curative aim, 89% had a full recovery. Postoperative complications occurred in half of the patients, but postoperative mortality was rare. CONCLUSIONS: The incidence of insulinomas has increased during the past three decades. Despite the improved diagnostic options, diagnostic delay has remained unchanged. To shorten the delay, clinicians should be informed and alert to consider the possibility of hypoglycemia and insulinoma, when symptomatic attacks are investigated in different sectors of the healthcare system. Developing the surgical treatment is another major target, in order to lower the overall complication rate, without compromising the high cure rate of insulinomas.

[Insulinomas in Tampere University Hospital Special Responsibility Area in 1980-2010]. / Insulinoomat Tampereen yliopistollisen sairaalan erityisvastuualueella 1980-2010.

BACKGROUND: Insulin-producing neuroendocrine tumours (iNETs) are rare, but their incidence is increasing. We studied the incidence, clinical picture, diagnostics, and treatment of insulinomas diagnosed in 1980 to 2010. METHODS: Retrospective analysis of insulinomas diagnosed in Tampere University Hospital. RESULTS: We found 23 iNET cases corresponding to an incidence of 0.7/million/year. All had neuroglycopenic symptoms and 83% had autonomic ones. The median diagnostic delay (from first symptoms up to diagnosis) was 25 months. Preoperative imaging found the tumor in 87%. Twenty-one out of 22 patients who underwent surgery recovered completely. CONCLUSIONS: Despite improved imaging the diagnostic delay of iNETs remained unchanged. Hypoglycemia and insulinoma should be considered as a cause of unspecific, symptomatic attacks.

Effects of erythropoietin treatment on cell-mediated immune responses in predialysis patients.

OBJECTIVE: The effects of erythropoietin (EPO) treatment on the immune functions of dialysis patients have been shown to be controversial and there are only limited data concerning predialysis patients. MATERIAL AND METHODS: Twenty-four predialysis patients with renal anemia were assigned to subcutaneous EPO treatment, and those in need (n=19) were additionally treated with i.v. iron every other week. We analyzed the effect of the start of EPO treatment on (i) lymphocyte and lymphocyte subclass counts, (ii) lymphocyte stimulation functions and (iii) persisting IgG-class antibody levels to the viral antigens of Epstein-Barr virus and cytomegalovirus. RESULTS: Our main findings were a decrease in the absolute lymphocyte count, combined with decreases in all the main lymphocyte subclass counts. The absolute number of cells with activation and memory markers remained constant, and therefore their proportion slightly increased. The proliferation responses to phytohemagglutinin, tuberculin and tetanus declined significantly, while the amount of IgG-class viral antibodies remained unchanged, meaning that the humoral side of immunity was not affected by the start of the EPO treatment. Similarly, the proliferation response to pokeweed mitogen, a B-cell mitogen, was unchanged. CONCLUSIONS: EPO treatment has a suppressive effect on cellular immune functions of predialysis patients. This suppression does not correlate with erythropoiesis, kidney function or iron status.

Influenza vaccination of dialysis patients: cross-reactivity of induced haemagglutination-inhibiting antibodies to H3N2 subtype antigenic variants is comparable with the response of naturally infected young healthy adults.

BACKGROUND: Annual influenza vaccination is recommended for patients with chronic renal failure, although vaccination responses in haemodialysis (HD) patients may be suboptimal. Typically, the seroreactivity has been analysed against the vaccine virus or the corresponding year's epidemic virus. No studies analysing cross-reactivity against subsequent years' viruses have been presented. METHODS: Twenty-three chronic HD patients and 26 cardiac patients were, in autumn 1995, vaccinated with a trivalent influenza vaccine. The cross-reacting haemagglutination-inhibiting antibodies to five consecutive years' (the last season 1999-2000) drift variants of H3N2 subtype influenza A virus were measured and compared with those of vaccinated cardiac patients and with those of 26 healthy military conscripts who suffered a serologically confirmed influenza A infection in the season 1995-1996. RESULTS: The influenza vaccination in HD patients resulted in comparable cross-reacting antibodies to the antibodies induced both by vaccination in cardiac patients and by natural infection in military conscripts. After a steady decline, the cross-reactivity to the latest epidemic virus improved in all the groups. This may be due to two reverted amino acid changes in the HA1 domain of the virus haemagglutinin. CONCLUSIONS: Influenza vaccination in HD patients is as effective as the vaccination of cardiac patients with normal kidney function. The cross-reactivity of vaccination-induced antibodies is even as good as that of antibodies induced by natural infection of young healthy males. Additionally, vaccination seems to prime the individual beneficially against subsequent years' influenza viruses.