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.

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.

Expression of thioredoxin, 8Hydroxy-deguanosine and peroxiredoxins in placental tissues.

In this study we analyzed the expression of 8-hydroxy-deguanosine (8OHdG), thioredoxin (Trx) and peroxiredoxins (Prx) 2, 3, 4, 5 and 6 in 80 cases of placental samples representing both normal and diseased placentas. The staining was evaluated separately in the stromal, trophoblastic and vascular components of the tissues. The results indicate that during the first trimester the level of reactive oxygen species (ROS) as indicated by 8OHdG was highest in the stromal component, which was also the case for Trx, Prx3, Prx4 and Prx6. In diseased placentas stromal 8OHdG was lower in cases with chromosomal aberrations but higher in molar disease in both trophoblastic and stromal cells. In chorioamnionitis stromal prx 5 and prx6 were high. Stromal prx4 and trophoblastic prx6 and stromal and endothelial Trx were also higher in molar disease. The results show that the oxidative stress is high in placentas during the first trimester. This probably reflects the oxidation burst of the placental tissues due to development of vascularity. In diseased placentas elevated levels of Prxs were seen in chorioamnionitis reflecting the ROS stress induced by inflammatory cells. The higher values of antioxidative enzymes in molar disease are possibly due to defective placentation. All in all, the results underline the importance on ROS associated mechanisms in placental development and the function of placenta to protect the developing fetus from harmful effects of reactive oxygen species as evidenced by their abundant expression in different cellular compartments of the placenta.

A survey of zeb1, twist and claudin 1 and 4 expression during placental development and disease.

We investigated zeb1, twist and claudins 1 and 4 in normal and diseased placental tissues. Eighty cases of placental tissues from all three trimesters and from different diseases were studied immunohistochemically to determine the expression of zeb1, twist and claudins 1 and 4. Zeb1 was more strongly expressed in endothelial and mesenchymal cells of the villous structures during the last two trimesters, suggesting that it plays a role in the development of placental blood vessels. In contrast, twist was more strongly expressed in the trophoblastic cells during these trimesters. The endothelial and stromal expression of zeb1 and the epithelial expression of twist were disturbed in those placentas with chromosomal aberrations. Claudin 4 was strongly expressed in trophoblastic cells during all trimesters. Its expression was especially strong in molar disease, suggesting that it could participate in trophoblastic aggregation and disturbed attachment of trophoblastic cells in the expanded villi. Claudin 4 expression was also increased in the placentas of diabetic mothers and in toxaemia. Claudin 1 did not show any specific disease associations. The study implicates that twist and zeb1 are involved in placental maturation, whereas claudin 4 appears to be connected with placental diseases such as diabetes, toxaemia or molar disease.

[Cronkhite-Canada syndrome - a rare intestinal polypotic syndrome]. / Cronkhite-Canadan oireyhtymä.

Cronkhite-Canada syndrome is a rare polypotic disease of the gastrointestinal tract. There are no specific diagnostic criteria for this syndrome. Suspicion may arise if both an endoscopic and a histopathologic finding together with the patient's symptom picture are indicative of the disease. Other polypotic conditions should be excluded. No established treatment is available for the syndrome. The principles of treatment have remained almost unchanged at least over the past decade. With a large proportion of the patients eventually developing a gastrointestinal malignancy, the prognosis of the disease is mostly poor.

Malignant giant cell tumor in the posterior fossa of a neonate.

Giant cell tumors (GCTs) of the bone are rare, usually benign but locally aggressive neoplasms that primarily occur in the epiphyses of long bones. They seldom develop in the cranium; when they do, they involve principally the sphenoid and temporal bones. These tumors usually affect young adults, and few reports in children have been published. Primary malignant GCTs of the skull are even more uncommon. The 3 published cases all involved adults over 40 years of age. Herein, the authors present a case of a highly aggressive primary malignant GCT of the posterior fossa in a 5-week old preterm infant. One month after the gross-total resection of the tumor found in the bone, the infant's condition rapidly deteriorated and she died. Magnetic resonance imaging and postmortem examination revealed a tumor larger than it had been before the operation, with expansion toward the brain. To the best of the authors' knowledge, this is the youngest patient reported with a primary malignant GCT of the skull, and actually the first case in a pediatric patient. In addition, the extremely high growth rate of the tumor in the postoperative period renders this case the most aggressive primary malignant GCT of the cranium described so far.

Cholesterol absorption decreases after Roux-en-Y gastric bypass but not after gastric banding.

The differences in cholesterol metabolism after the 2 most common forms of obesity surgery, Roux-en-Y gastric bypass (RYGB) and gastric banding (GB), have not been well characterized. In this study, effects of RYGB and GB on cholesterol absorption and synthesis were investigated. To this aim, 1-year follow-up of cholesterol metabolism in 2 nonrandomized cohorts undergoing either RYGB (n = 29; age, 45.2 +/- 7.7 years; body mass index [BMI], 46.0 +/- 6.1 kg/m(2)) or GB (n = 26; age, 45.9 +/- 8.6 years; BMI, 50.1 +/- 7.7 kg/m(2)) was performed in a university hospital center specializing in the treatment of morbid obesity. Serum markers of cholesterol synthesis (cholestenol, desmosterol, and lathosterol) and cholesterol absorption (campesterol, sitosterol, avenasterol, and cholestanol) were measured preoperatively and at follow-up and expressed as ratios to cholesterol. As expected based on observed weight loss (25% after RYGB and 17% after GB, P < .001 between groups), both operations decreased serum levels of cholesterol synthesis markers by 12% to 28% (all Ps < .001). A decrease in cholesterol absorption markers was only observed after RYGB (-26% for sitosterol) and not after GB (+16%, P = 2 x 10(-6) for difference between the groups). The difference in sitosterol ratio between the groups remained significant after adjustment for age, BMI, fasting insulin levels, and nutritional status (P = 2 x 10(-4)), indicating a specific effect related to RYGB. We conclude that decrease in cholesterol absorption is a novel beneficial effect of RYGB. Together with an improved control of blood glucose, this may contribute to a better cardiovascular risk profile after RYGB.

Smooth muscle tumor of the placenta - an entrapped maternal leiomyoma: a case report.

INTRODUCTION: Neoplasms of the placenta are uncommon. Tumors arising from the placental tissue include two distinct histological types: the benign vascular tumor, chorangioma, and very rarely, choriocarcinoma. Benign leiomyomas, in contrast, are very common tumors of the uterine wall and occur in 0.1% to 12.5% of all pregnant women. However, the incorporation of uterine leiomyoma into the placenta is exceptional and raises the question of its origin. This case is possibly the first report on this kind of a placental tumor which has been examined using both immunohistochemistry and chromosome analysis. CASE PRESENTATION: A 34-year-old G4P3 Caucasian woman was followed up antenatally because of a stillbirth in her previous pregnancy. At 36 weeks' gestation, a hypoechoic, 3.6 x 4.2 cm rounded mass was noted within the placenta on ultrasound examination. Histologically, the tumor was a benign leiomyoma and this finding was supported by immunohistochemistry. The newborn infant was male. Chromosomes of the neoplasm were studied by the fluorescence in situ hybridization technique and the tumor was found to carry XX chromosomes. CONCLUSION: A rare benign smooth muscle neoplasm involving the placental parenchyma is presented. The tumor was a uterine leiomyoma of maternal origin, which had become entrapped by the placenta. This case report is of interest to the clinical specialty of obstetrics and gynecology and will advance our knowledge of the etiology of placental tumors.

Congenital Langerhans cell histiocytosis mimicking a "blueberry muffin baby".

Congenital Langerhans cell histiocytosis (LCH) is a rare condition with great diversity. A case of congenital skin-only LCH presenting as a "blueberry muffin baby" with a spontaneous regression by the age of 8 months is reported here. New insights into clinical manifestations and prognosis, which is not uniformly positive, are discussed. A thorough examination and a careful follow-up should be provided to these patients. Systemic therapy is warranted in multi-system disease; no consensus on treatment exists in case of LCH isolated to skin. The diagnosis of congenital self-healing LCH should be made only retrospectively.

Long-term results, late complications and quality of life in a series of adjustable gastric banding.

BACKGROUND: Adjustable gastric banding is currently the most common bariatric operation. This study is a retrospective analysis of the Finnish experience with this procedure over the last 10 years. METHODS: Between March 1993 and June 1999, 123 patients underwent either open (36) or laparoscopic (87) surgery for morbid obesity by the application of an adjustable gastric band. Data on preoperative clinical characteristics and postoperative outcome and weight-loss patterns up to 9 years (mean 55 months) are presented and also evaluated by the Bariatric Analysis and Reporting Outcome System (BAROS). Sex ratio was 31% males / 69% females, mean age 44 years and mean +/- SD preoperative BMI 49 +/- 8 kg/m(2) (range 33.6-85.1). RESULTS: During the evaluation period (March 1993 December 2002), 54% of patients experienced postoperative complications requiring hospital treatment >or= 7 days, and 52% underwent a reoperation. 33% of bands were removed. The most important late complications were esophagitis (30%), obstruction due to slippage / pouch dilatation (21%), incisional hernia (9%) and band erosion (9%). Mean excess weight loss at 1 and 2 year follow-up was 36% and 38%, which later stabilized to 30%. During the evaluation period, there were 10 deaths, 2 of which were 30-day deaths, and the remainder were not associated with the band. According to BAROS, the outcome was regarded as "very good" in 3%, "good" in 7%, "fair" in 40% and "failure" in 50%. CONCLUSION: Our long-term data found that weight reduction is acceptable,but the incidence of late complications and reoperations was high.