Incidence of myeloproliferative neoplasms - trends by subgroup and age in a population-based study in Sweden.

BACKGROUND: The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. OBJECTIVE: We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. METHODS: Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. CONCLUSION: The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.

Time-resolved X-ray diffraction investigation of the modified phonon dispersion in InSb nanowires.

The modified phonon dispersion is of importance for understanding the origin of the reduced heat conductivity in nanowires. We have measured the phonon dispersion for 50 nm diameter InSb (111) nanowires using time-resolved X-ray diffraction. By comparing the sound speed of the bulk (3880 m/s) and that of a classical thin rod (3600 m/s) to our measurement (2880 m/s), we conclude that the origin of the reduced sound speed and thereby to the reduced heat conductivity is that the C44 elastic constant is reduced by 35% compared to the bulk material.

The most common chromosome aberration detected by high-resolution comparative genomic hybridization in vulvar intraepithelial neoplasia is not seen in vulvar squamous cell carcinoma.

We analyzed genetic changes in condylomas (four cases), vulvar intraepithelial neoplasia I-III (VIN I-III, eleven cases), and primary vulvar squamous cell carcinomas (VSCC, ten cases) by high-resolution comparative genomic hybridization (HR-CGH) and flowcytometry. All samples were also human papilloma virus (HPV)-genotyped. Gain of chromosome 1, the aberration most often seen in VIN III (67%), was not seen in HPV-positive or -negative VSCCs (0%). Both VIN III and VSCC frequently showed gain of 3q (56 and 70%, respectively). The VIN III samples often demonstrated gain of 20q (56%) and 20p (44%), and the VSCC samples gain of 8q (60%), loss of 3p (50%), and 8p (40%). None of the four most frequent changes in the VSCC samples occurred exclusively in the HPV-positive or -negative samples. As expected, we did not find any cytogenetic changes in condylomas and nearly any changes in VIN I-II.

Neuroendocrine dysfunction in galactorrhea-amenorrhea after oral contraceptive use.

Nonpuerperal alactorrhea and amenorrhea have been reported following the use of oral contraceptives. Treatment of this condition with ergot alkaloids has proved to be of great therapeutic value. Pretreatment plasma hLH and hFSH concentrations in 13 women with postqill galactorrhea-amenorrhea (PPGA) were 6.6 plus or minus 0.6 (SE.) and 5.0 plus or minus 0.8 mlU/ml, respectively. The mean prolactin concentration was 80.7 plus or minus 13.2 ng/ml. After complete evaluation in which diagnostic evidence of pituitary tumor was absent, the patients were treated with ergocryptine (CB-154). The mean hPRL concentration at 14 days of therapy was 7.8 p;us or minus 1.9 ng/ml. Cyclic gonadotropin secretion resumed in all but one instance; ovulation was confirmed on the basis of a biphasic temperature chart and in 5 cases, endometrial biopsy. Measurement of serum dopamine-beta-hydroxylase (DBH) activity indicated a significant decline at the end of 8 weeks of CB-154 therapy. The fall in hPRL was not necessarily associated with a fall in DBH. The majority of women in this study exhibited a consistent personality suggesting varying degrees of anxiety unrelated to the PPGA and usually antedating the use of oral contraceptives. PPGA was found in women without hyperprolactinemia, but altered hPRL secretion was evident in all instances. The data suggest that the disorder of cyclic gonadotropin secretion is related to altered hPRL secretion, but the mechanism is possibly related to a catecholamine abnormality. The data support the presence of an inherent cyclic mechanism for the secretion of gonadotropins. CB-154 therapy does not affect conception, and no teratogenic effects were observed in 2 infants born to women who had received CB-154 during the first 40 days of gestation.

Plasma erythropoietin in essential thrombocythaemia: at diagnosis and in response to myelosuppressive treatment.

Sixty-five patients with essential thrombocythaemia (ET) on different treatment regimens were studied with regard to EDTA-plasma erythropoietin (EPO) concentrations. In accordance with other studies we found that close to 50% of the untreated ET patients had subnormal (<3.7 IU/L) plasma EPO. The mean plasma EPO concentration for untreated ET patients was significantly lower compared to patients treated with hydroxyurea (HU), radiophosphorous, alpha-interferon or combinations of myelosuppressive agents. This was also true after correction for differences in haemoglobin concentrations had been introduced. An increase in plasma EPO was recorded in all 20 ET patients in whom plasma EPO was registered before and after initiation of myelosuppressive therapy. At the time of diagnosis plasma EPO concentration was available in 31 of the ET patients. In 13 of them the plasma EPO was subnormal whereas the EPO concentrations were > or =3.7 IU/L in the remaining 18 subjects. It was demonstrated that the time to initiation of myelosuppressive treatment was significantly shorter for the former group of patients; they also had more vascular events (11 out of 13) than the group of patients with plasma EPO concentrations > or =3.7 IU/L (9 out of 18). It therefore appears that a subnormal plasma EPO in newly diagnosed ET might be a risk factor for the development of vascular complications.

The relation between plasma thrombopoietin and erythropoietin concentrations in polycythaemia vera and essential thrombocythaemia.

Plasma thrombopoietin (TPO) was measured, by immunoenzymometric assay, in 39 patients with polycythaemia vera (PV), 33 patients with essential thrombocythaemia (ET) and 10 healthy volunteers. The mean TPO concentration was significantly higher in ET patients than in PV patients (p=0.04) and normals (p<0.001). The 6 untreated ET patients had a significantly lower mean TPO concentration compared to the 27 ET patients who were on myelosuppressive regimens (p=0.01). The mean plasma TPO for the 5 PV patients treated with phlebotomy only did not differ significantly from the corresponding mean for the 34 PV patients treated with myelosuppressive agents. Concomitantly, plasma EPO was measured in 25 of the PV patients and in 30 of the ET patients by an immunoradiometric assay with normal reference interval in adults 3.7-16 IU/L. In the 14 PV patients with EPO <3.7 IU/L mean plasma TPO did not differ significantly from the mean for the 11 PV patients with EPO >or=3.7 IU/L; neither of these two groups had plasma TPO concentrations significantly different from the mean for the control subjects. The 7 ET patients with subnormal plasma EPO had significantly lower mean plasma TPO compared to the ET patients with normal and high plasma EPO concentrations (p=0.03 and p=0.02, respectively). Also, the 16 ET patients with normal plasma EPO had significantly lower plasma TPO compared to the 8 patients with high plasma EPO (p=0.04). The mean plasma TPO for each of these three groups of ET patients was significantly higher than the corresponding mean for the controls (p<0.001 for each group). The results of the present study indicate that a relationship between plasma EPO and TPO concentrations may exist and that myelosuppressive treatment affects the TPO concentration in ET but not in PV patients.

Plasma erythropoietin concentrations in polycythaemia vera with special reference to myelosuppressive therapy.

In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.

Effects on respiration of CPAP immediately after extubation in the very preterm infant.

The effects of continuous positive airway pressure (CPAP) on pulmonary function during weaning from ventilator treatment were examined immediately after extubation in 17 very preterm infants, who had been ventilator-treated because of hyaline membrane disease (15 infants) and chronic pulmonary insufficiency of prematurity (two infants). Seven infants had bronchopulmonary dysplasia. Median birthweight was 920 g and median gestational age 26 completed weeks. The median duration of ventilator treatment was 10 days. Application of CPAP by means of a face chamber device after endotracheal extubation significantly lowered the frequency of apnea (P = 0.02) and enhanced oxygenation (P = 0.001). The respiratory mechanical indices derived from flow rate and juxta-diaphragmatic esophageal pressure measurements showed a reduced elastic (P = 0.03) and resistive (P = 0.02) load on the diaphragm. Even if the measured values do not accurately represent absolute resistances and compliances, the relative values of end-inspiratory and end-expiratory pressures differed significantly with and without CPAP (P = 0.001 and 0.002, respectively). We found CPAP applied via the face chamber technique immediately after extubation to be beneficial and to facilitate weaning from ventilator treatment in very preterm infants.

Thoracoabdominal motion in newborns during ventilation delivered by endotracheal tube or nasal prongs.

Preterm infants have asynchronous thoracoabdominal motion (TAM) secondary to a highly compliant chest wall and different lung mechanics compared to term infants. We compared TAM during continuous positive airway pressure (CPAP) administered through an endotracheal tube (ETT-CPAP) or nasal prongs (nasal-CPAP), and during synchronized intermittent mandatory ventilation administered by nasal prongs (nasal-SIMV) in 14 preterm newborn infants. Asynchrony of TAM was quantified by measuring relative motion of chest wall and abdomen with strain gauges and calculating phase angles (theta). Phase angles were lower during nasal-SIMV compared to nasal-CPAP or ETT-CPAP (P < 0.05), and lower during nasal-CPAP compared to ETT-CPAP (P < 0.05). The reduced TAM asynchrony during nasal-SIMV and nasal-CPAP may be due to elimination of resistance of the ETT and/or effective stabilization of the chest wall. These data suggest that nasal-SIMV may be an effective mode of respiratory support for preterm infants requiring minimal ventilatory support.

Value of four models for selecting patients for local excision of invasive squamous cell carcinoma of the vulva.

For 75 women with squamous cell carcinoma of the vulva who underwent radical vulvectomy and inguinofemoral lymphadenectomy, the authors assessed the efficacy of four models for selecting patients who could have been treated adequately with local excision of the tumor. Each of the three models proposed by Andreasson and Nyboe covered 25% of the patients, none of whom had groin metastases or died of cancer. Local recurrence in the vulva occurred in 10%. A model suggested by the International Society for the Study of Vulvar Disease covered almost 10% of the patients. One of seven patients had groin metastases, none died of cancer, and one of seven developed local recurrence in the vulva. The criteria of the clinically best suited model are tumor not situated on the clitoris and less than 4 cm in diameter, with only slight hyperchromasia. This model ought to be tested in a randomized study.

[Difficulties in early differential diagnosis of intra/extrauterine pregnancy]. / Differentialdiagnostiske vanskeligheder ved tidlig intra/ekstrauterin graviditet.

Employing the new very sensitive pregnancy tests, pregnancy can be confirmed several weeks before it can be visualized by ultrasonic scanning or can be seen at laparoscopy or laparotomy. This involves the risk that unnecessary diagnostic interventions are performed in early pregnancy with symptoms suggestive of extrauterine pregnancy. Three case reports are quoted to illustrate the problems involved.

[Estrogen replacement to women treated for endometrial cancer]. / Ostrogensubstitution til kvinder behandlet for endometriecancer.

Oestrogen replacement therapy in women treated for endometrial cancer has long been considered contra-indicated. Based on a review of the literature, which shows a low risk of recurrence during oestrogen replacement therapy in women treated for low-risk endometrial cancer, we advocate that this group of patients could be offered oestrogen replacement therapy and be provided with the benefits of prevention of cardiovascular disease and osteoporosis. Further studies are needed to investigate the survival and recurrence rates of high-risk patients treated with oestrogen replacement therapy.

[Estrogen replacement in women treated for breast cancer]. / Ostrogensubstitution til kvinder behandlet for mammacancer.

Oestrogen replacement therapy in women with a history of breast cancer has long been considered contraindicated. However, the literature does not indicate an increased risk of recurrent breast cancer in postmenopausal women receiving oestrogen replacement therapy. We advocate that women with a history of breast cancer without nodal involvement could be offered oestrogen replacement therapy and thereby benefit from prevention of cardiovascular disease and osteoporosis. But the patients must accept a potentially increased risk of recurrence. We emphasize the need for randomized prospective studies.

[Atypical endometrial hyperplasia. Prognosis and course]. / Atypisk hyperplasi i endometriet. Prognose og forløb.

The treatment of patients with the diagnosis atypical endometrial hyperplasia has been disputed during the last decades. The aim of the study was to evaluate the treatment of these patients and analyse the progression rate to invasive carcinoma of the endometrium. Fifty-seven patients with atypical hyperplasia were examined and treated from 1976 through 1991. The medical records were examined retrospectively and the pathology slides were revised by one pathologist in accordance with the 1975 WHO recommendations. Thirty-one (54%) patients were on oestrogen treatment as monotherapy at the time of diagnosis. Forty-two patients had a hysterectomy performed within five months, and five patients had a hysterectomy performed 10 to 61 months after diagnosis. A total of 18 out of 57 patients (31.6%) had or developed endometrial carcinoma all with myometrial invasion: 14 stage I with < or = 50% myometrial invasion, three stage I with > 50% myometrial invasion, and one stage IV. There was no significant difference in age, body mass index, parity or hormone replacement treatment between the group with endometrial carcinoma and the group without endometrial carcinoma. We conclude that unopposed oestrogen treatment and nulliparity are the main risk factors for atypical hyperplasia and that hysterectomy is the appropriate treatment for patients with atypical hyperplasia of the endometrium.

[Treatment of cervix cancer in Denmark]. / Behandlingen af cancer cervicis uteri i Danmark.

The current status of cervical cancer treatment in Denmark is discussed. Diagnostic aspects and problems of classification are presented briefly supplemented with a comment on new prognostic parameters based on a semiquantitative score system and flow cytometry. Surgery is the treatment of election for the early stages whereas radiotherapy is the treatment of choice in advanced stages. Chemotherapy should only be employed in the framework of clinical trials. It is concluded that centralised treatment should be maintained.

The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries.

Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.