Lung cancer registries in Denmark, Finland, Norway and Sweden: a comparison and proposal for harmonization.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in all Nordic countries which, though similar in demographics and healthcare systems, have noticeable differences in lung cancer survival. Historically, Denmark and Finland have had higher lung cancer incidences and lower survival than Norway and Sweden. All four countries have national cancer registries. Data in these registries are often compared, but their full potential as a source of learning across the Nordic countries is impeded by differences between the registries. In this paper, we describe and compare the Nordic registries on lung cancer-specific data and discuss how a more harmonized registration practice could increase their usefulness as a source for mutual learning and quality improvements. METHODS: We describe and compare the characteristics of data on lung cancer cases from registries in Denmark, Finland, Norway and Sweden. Moreover, we compare the results from the latest annual reports and specify how data may be acquired from the registries for research. RESULTS: Denmark has a separate clinical lung cancer registry with more detailed data than the other Nordic countries. Finland and Norway report lung cancer survival as relative survival, whereas Denmark and Sweden report overall survival. The Danish Lung Cancer Registry and the Swedish Cancer Registry do not receive data from the Cause of Death registries in contrast to the Finnish Cancer Registry and the Cancer Registry of Norway. CONCLUSION: The lung cancer registries in Denmark, Finland, Norway and Sweden have high level of completeness. However, several important differences between the registries may bias comparative analyses.

Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study.

Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer. Patients and methods: Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR). Results: Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety profile was comparable between carboplatin/paclitaxel arms. Adverse events (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with VT versus PCP. Conclusion: Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population. Clinical trial information: NCT01506609.

Consequences of persistent pain after lung cancer surgery: a nationwide questionnaire study.

BACKGROUND: post-thoracotomy pain syndrome (PTPS) and its social consequences have been inconsistently investigated as most studies were either small sized, focused on a limited number of risk factors or included heterogeneous surgical procedures. The current objectives were to obtain detailed information on the consequences of PTPS after thoracotomy and video-assisted thoracic surgery (VATS) from homogenous unselected nationwide data, and to suggest mechanisms for the development of PTPS. METHODS: data from 1327 patients were collected using a prospective national database and combined with a detailed questionnaire. RESULTS: the response rate was 81.5%, resulting in 546 patients without prior thoracic surgery for the final analysis. Follow-up was 22 months (range 12-36). PTPS occurred in 33% thoracotomy patients and 25% VATS patients. Clinically relevant pain was present in 11-18% of the patients and severe pain in 4-12% depending on the level of physical activity. In PTPS patients, 64% also had pain from other locations on the body. Perceived sensory changes in the thoracic area were present in 63% of PTPS patients vs. 25% in pain-free patients (P<0.001). When comparing VATS with thoracotomy, no consistent differences in the prevalence, distribution of pain, sensory changes or effect of pain on daily activities were observed although clinically relevant and severe pain was reduced after VATS. CONCLUSIONS: this nationwide study corroborates that PTPS is a clinically relevant problem influencing daily activities a long time after thoracotomy and VATS. Nerve injury and increased pain responsiveness may explain the majority of symptoms, the prevalence and distribution of pain including perceived sensory sensations.

Impact of health care organization on surgical lung cancer care.

OBJECTIVES: Organization and governance of national healthcare might play an important role in decision-making and outcomes in patients with lung cancer. Both Denmark and the Netherlands have a high level of healthcare but a different financial coverage, governance and level of centralization. By using both national databases we analyzed the consequences of these differences on patterns of care and outcomes with a focus on morbidity, mortality and clinical staging. MATERIALS AND METHODS: General numbers on both healthcare systems were requested. All patients who had surgery for lung cancer from 2013 to 2016 were included. Mortality, morbidity and clinical staging were analyzed for patients with NSCLC without metastases, only one operation and no neo-adjuvant therapy. RESULTS: In 2016 annual budget as share of gross national product was 10.4% for both countries. In Denmark 4 hospitals performed lung surgery in 2016, compared to 43 hospitals in the Netherlands. We included 4030 Danish and 8286 Dutch patients. In the subgroup 30-day mortality was 1.5% in Denmark compared to 1.9% in the Netherlands. The percentage of patients with a complicated course was 24.4% and 34.8% respectively (p < 0.05). Accuracy between cTNM and pTNM was 53.0% in Denmark and 52.9% in the Netherlands. CONCLUSION: Surgery for lung cancer is at a high level in both countries, reflected by low mortality-rates. Centralization has been implemented successfully in Denmark, which might explain the lower rate of patients with a complicated post-operative course, although different definitions preclude firm conclusions. In both countries correct clinical staging of lung cancer remains a challenge.

History of Depression in Lung Cancer Patients: Impact of Delay.

AIMS: To examine the influence of a history of depression in the process of diagnostic evaluation and the choice of treatment in lung cancer. MATERIALS AND METHODS: The analysis was based on all patients with non-small cell lung cancer who were registered in 2008-2014; in total, 27 234 patients. To estimate the effect of depression on the diagnostic process and the choice of treatment in lung cancer we fitted a logistic regression model and a Cox regression model adjusting for age, gender, resection and stage. RESULTS: Depression in a patient's anamnesis had no significant effect on the delay in diagnostic evaluation (hazard ratio = 0.99 with 95% confidence interval 0.90; 1.09). Patients with a history of periodic depression had a 33% lower treatment rate (odds ratio = 0.66 with 95% confidence interval 0.51; 0.85) than patients without a history of depression. CONCLUSIONS: Our study shows that patients with a history of periodic depression need special attention when diagnosed with lung cancer.

Within- and across-person uniformity of body condition scoring in Danish Holstein cattle.

Body condition scores (BCS) are very useful for dairy herd management and breeding programs, but the consistency and quality of recordings made by consultants in the field are unknown. The objectives of this study were 1) to estimate the agreement in BCS within and among practicing dairy veterinarians and 2) to provide an indication of the effects of training and the value of calibration, and of what efforts need to be made to obtain a validity and precision in BCS adequate for management purposes. A total of 2,230 scores were recorded by 51 practicing dairy veterinarians and 6 highly trained instructors. The 6 instructors were cross-trained to validate calibration consistency in assigning BCS. Each individual scored approximately 20 cows twice, with the second scoring occurring approximately 2.5 h after the first. Between the 2 recordings, the respective instructors conducted a training session for the practicing veterinarians using other cows. A weighted kappa coefficient was used to assess agreement among and within classifiers. Excellent agreement (kappa > or = 0.86) was documented between repeated BCS recorded for the same cows by the highly trained instructors. In addition, the BCS provided by multiple classifiers from the instructor team appeared to be comparable across herds and classifiers. This legitimizes the use of BCS for benchmarking at both the cow and the herd level. The within-classifier and between-classifier kappa values were in the ranges of 0.22 to 0.75 and 0.17 to 0.78, respectively, in the group of practicing dairy veterinarians. Many of the veterinarians provided estimates of average BCS that differed considerably from the BCS recorded by the instructors. Between-classifier comparisons of herd BCS are not warranted unless a validation has been performed. If scores are collected by multiple classifiers with varying experience, a valid but imprecise estimate of the true population mean of BCS may be obtained if classifiers are inexperienced. The limited training effort used in this study seemed to have brought about substantial improvement in the validity and precision of the BCS determined by practicing veterinarians, compared with the BCS recorded on the same cows by highly trained classifiers.

Successful clinical use of an anti-HLA-DR monoclonal antibody for autologous bone marrow transplantation.

It has been widely assumed that anti-HLA-DR antibodies react with pluripotent stem cells and cannot be used in bone marrow purging. We report a case of non-Hodgkin's lymphoma in which an anti-HLA-DR antibody (AB4) was used for immunomagnetic purging and the subsequent autologous bone marrow transplantation resulted in rapid marrow engraftment with no serious complications. The results indicate that the AB4 antibody, which binds to an antigen encoded by the B3 gene of the DR region, can be safely used in the clinic in the purging of bone marrow from patients with AB4-positive tumors (non-T-cell acute lymphocytic leukemia, non-Hodgkin's lymphoma, and some cases of acute myelogenous leukemia.

Parents' experiences of collaboration with community healthcare professionals.

Over the last decades there has been a reduction in the number of institutional beds in psychiatric care in Norway. This has led to more psychiatric patients being dependent on community care and consequently an increased need for collaboration with the parents of these patients. In most cases parents are an important source of support in helping patients manage their everyday life. The aim of this study was to explore how parents of adult psychiatric patients experience collaboration with health professionals in the community healthcare services. The data collection in this study is based on 12 interviews with six parents, and a qualitative analysis method was employed. Four themes emerged: (1) communication and relationship between parents and health professionals; (2) lack of information; (3) parents' participation in the treatment of their son or daughter; and (4) the need for guidance and support. It was reported that health professionals are suspicious of parental involvement and often refuse to allow them to participate in the care. Further research on parents' experiences of collaboration is necessary. The value of parents as an important source of support can be enhanced by means of increased collaboration.

Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma.

Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma patients. Twelve patients with Hodgkin's disease (HD) and 38 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3 to 20) of chemotherapy prior to mobilization. It was found that the optimal time of PBPC harvest was at days 12 and 13 after initiating the mobilization regimen. The median number of collected CD34+ cells per kg body weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 69% of the patients after one apheresis. When additional cycles of apheresis were done, only 6% failed to harvest this number of CD34+ cells. There was a statistically significant inverse correlation between the number of prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more efficient in mobilizing PBPC in spite of being less myelotoxic. All patients transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF can be successfully used to mobilize PBPC.

Activation of coagulation and deep vein thrombosis after bone marrow harvesting and insertion of a Hickman-catheter in ABMT patients with malignant lymphoma.

Evidence of activation of coagulation was sought in serial plasma samples from 25 ABMT candidates with malignant lymphoma admitted for bone marrow harvesting: 10 females and 15 males, median age 41 years (range 27-58 years). Nineteen patients had non-Hodgkin's lymphoma (NHL) and six had Hodgkin's disease. Of those with NHL, 14 had high-grade and five low- grade disease. The plasma levels of markers of activation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, fibrinopeptide A and fibrinmonomers) increased significantly (P < 0.001) in association with harvesting. Except for fibrinopeptide A, the indicators of activation were still significantly elevated 24 h after marrow aspiration. Beta-thromboglobulin, a marker of the platelet release reaction, also increased significantly (P < 0.01). Four out of nine patients in whom a long-term central venous catheter was inserted just after marrow aspiration, developed catheter-related deep vein thrombosis, verified venographically, shortly after harvesting. These results suggest that patient with malignant lymphoma undergoing marrow harvesting develop a hypercoagulable state, and that insertion of a central intravenous catheter immediately after marrow harvesting should be avoided to prevent the development of symptomatic deep vein thrombosis.

An effective immunomagnetic method for bone marrow purging in T cell malignancies.

An immunomagnetic method was developed to purge human bone marrow of malignant T cells, for use in conjunction with autologous bone marrow transplantation in patients with acute lymphoblastic leukemia and lymphoma. Three monoclonal antibodies anti CD2 (BH1), CD5 (BB8) and CD7 (BF12) were used. In model experiments employing MOLT4 cells it was found that with 50-fold excess of immunobeads relative to antigen-positive cells, the use of each antibody alone resulted in a 3.3-3.6 log tumor cell depletion, as assessed in a sensitive and reproducible clonogenic soft agar assay. When all three antibodies were used in a mixture, a purging efficacy of 5 logs was achieved. Two treatment cycles improved these figures to about 4 logs and more than 5 logs. When MOLT4 cells were mixed 1:10 with fresh bone marrow cells the antibody mixture yielded 3.1 and more than 5 log tumor cell depletion with one and two treatment cycles, respectively. This procedure resulted in only an insignificant reduction of the number of CFU-GM and CFU-GEMM progenitor cells. In two patients autotransplanted with purged marrow, the loss of CFU-GM was 37% and 48%, and no tumor cells could be detected by immunocytochemistry after purging. Rapid and sustained engraftment was achieved and both patients remain in complete remission after more than 20 months.

Immunomagnetic removal of B-lymphoma cells from human bone marrow: a procedure for clinical use.

B-lymphoma cells were purged from human bone marrow by incubating the cell suspension with a cocktail of three different pan-B cell mouse IgG1 monoclonal antibodies, and then with immunobeads charged with sheep anti-mouse antibody, followed by magnetic separation. The primary antibodies used, HD37 (CD19), HD6 (CD22), and HH1 (CD37), bind to a very high percentage of the cells in non-Hodgkin's lymphomas of poor prognosis. The secondary antibody is directed against the Fc portion of the IgG antibodies. In model experiments Burkitt's lymphoma cells (Rael) were admixed to mononuclear bone marrow cells in the ratio 1/9. With a ratio of immunobeads/total antibody-binding B cells of 50/1 in a first treatment cycle and repeating the procedure with the same number of beads in a second cycle, a tumor cell depletion of more than 5 logs was achieved, as judged by a clonogenic assay. The concomitant reduction of CFU-GM and CFU-GEMM was about 20%. The purging procedure has been scaled up to clinical use. Equipment suitable for purging patients' marrow specimens, employing standard transfusion facilities, is described. With this equipment the efficacy of tumor cell removal was the same as in the model experiments, and the whole magnetic separation could be completed in 2 hours.

Therapeutic consequences of oesophageal function studies in patients with benign oesophageal disease.

Evaluation of oesophageal function was performed in 91 patients referred to a specialized department of cardiothoracic surgery for surgical treatment of benign oesophageal disease. Standard manometry was used in addition to radiology and endoscopy, and in some patients, an acid perfusion test, an acid clearing test, and a prolonged monitoring of pH in the distal oesophagus were additionally performed. The aim of this study was to evaluate whether assessment of oesophageal function is needed in such a patient group, and whether the results of these investigations were taken into account when making the final decision for therapy. Eleven percent of the patients referred with a diagnosis of hiatal hernia or reflux had achalasia or oesophageal spasm. Nine percent of the patients referred for motility disorders had reflux-related disease. The referral diagnosis was changed to a diagnosis with a different therapeutic approach in 16% of the patients. In 33%, a diagnosis of disordered oesophageal function was considered either at referral or during the routine assessment for oesophageal disease. Eighty-one percent of the patients with achalasia were treated in accordance with the manometric results. In all cases where an anatomical diagnosis was replaced by a diagnosis of disordered function, the treatment was in accordance with the findings of the motility studies. None of the patients with oesophageal spasm were suspected of having this disease. It is concluded, that not only anatomical features, but also functional considerations have to be taken into account when selecting treatment for benign oesophageal disease. Treatment failure and unnecessary surgical intervention can thus be avoided.

Whole-body distribution of radioactivity after intraperitoneal administration of 32P colloids.

The whole-body distribution of radioactivity after intraperitoneal instillation of 32P-labelled chromic hydroxide particles has been studied in patients operated for early-stage ovarian cancer. Gamma-camera imaging of the abdominal 32P-distribution revealed that the administration procedure was critical for obtaining a homogeneous plating of the radiocolloids on the serosal surface. Dose calculations based on a uniform distribution of 32P in a capillary layer covering the intraperitoneal surface gave an estimated tissue surface dose of about 30 Gy per 370 MBq of 32P administered. The amount of 32P in peripheral blood increased for seven days after instillation followed by a continuous decrease. Bone marrow concentration was from two to five times as high as that in blood, but the total amounts were too small to give significant radiation doses. Gel chromatography showed that 33% of the activity in blood consisted of high molecular weight material, probably colloids. The remainder of the activity (67%) was attached to material of very low molecular weight, appearing as a consequence of physiological degradation of the colloids.

Neural network for automatic analysis of motility data.

Continuous recording of intraluminal pressures for extended periods of time is currently regarded as a valuable method for detection of esophageal motor abnormalities. A subsequent automatic analysis of the resulting motility data relies on strict mathematical criteria for recognition of pressure events. Due to great variation in events, this method often fails to detect biologically relevant pressure variations. We have tried to develop a new concept for recognition of pressure events based on a neural network. Pressures were recorded for over 23 hours in 29 normal volunteers by means of a portable data recording system. A number of pressure events and non-events were selected from 9 recordings and used for training the network. The performance of the trained network was then verified on recordings from the remaining 20 volunteers. The accuracy and sensitivity of the two systems were comparable. However, the neural network recognized pressure peaks clearly generated by muscular activity that had escaped detection by the conventional program. In conclusion, we believe that neurocomputing has potential advantages for automatic analysis of gastrointestinal motility data.

Non-parametric classification of esophagus motility by means of neural networks.

Automatic long-term recording of esophageal pressures by means of intraluminal transducers is used increasingly for evaluation of esophageal function. Most automatic analysis techniques are based on detection of derived parameters from the time series by means of arbitrary rule-based criterions. The aim of the present work has been to test the ability of neural networks to identify abnormal contraction patterns in patients with non-obstructive dysphagia (NOBD). Nineteen volunteers and 22 patients with NOBD underwent simultaneous recordings of four pressures in the esophagus for at least 23 hours. Data from 21 subjects were selected for training. The performances of two trained networks were subsequently verified on reference data from 20 subjects. The results show that non-parametric classification by means of neural networks has good potentials. Back propagation shows good performance with a sensitivity of 1.0 and a specificity of 0.8.

Cells in peripheral leg lymph of normal men.

The cells of human peripheral lymph collected from leg lymphatic of healthy volunteers have been studied by light- and electron microscopy. More than 80% of the cells were lymphocytes. The rest of the cells were neutrophils, monocytes, phagocytes, intermediate forms between lymphocytes and monocytes, erythrocytes and large cells. Ultrastructurally these large cells had many features in common with the Langerhans cells of normal epidermis and may represent this cell type or a closely related one.

["Blue rubber bleb nevus syndrome"--or Bean's syndrome]. / "Blue rubber bleb naevus syndrome"--eller Beans syndrom.

We describe a case of the blue rubber bleb naevus syndrome, an uncommon systemic disorder characterized by multiple bluish haemangiomas of the skin and gastrointestinal tract. The syndrome is commonly associated with iron deficiency anaemia due to gastrointestinal bleeding. The syndrome is likely to be caused by a gene mapping to chromosome 9p and showing autosomal dominant inheritance. This is the first Danish report of this unusual disease. We hope that this case will heighten the awareness of this condition, because early recognition is essential for appropriate medical intervention and genetic counselling.

Challenging the myth of the irrational dairy farmer; understanding decision-making related to herd health.

Veterinarians working with dairy cows are suggested to refocus their efforts from being task-oriented providers of single-cow therapy and develop themselves into advice-oriented herd health management advisors. The practising cattle veterinarian's ability to translate knowledge into on-farm application requires a profound understanding of the dairy farm as an integrated system. Consequently, educating and motivating farmers are key issues. To achieve such insight the veterinarian needs to work with several scientific disciplines, especially epidemiology and (behavioural) economics. This trans-disciplinary approach offers new methodological possibilities and challenges to students of dairy herd health management. Advisors working with dairy herd health management may sometimes experience that farmers do not follow their advice. Potentially, this could lead to the interpretation that such farmers are behaving irrationally. However, farmers who are confronted with advice suggesting a change of behaviour are placed in a state of cognitive dissonance. To solve such dissonance they may either comply with the advice or reduce the dissonance by convincing themselves that the suggested change in management is impossible to implement. Consequently, herd health management advisors must understand the fundamental and instrumental relationships between individual farmers' values, behaviour and perception of risk, to stimulate and qualify the farmer's decision-making in a way that will increase the farmer's satisfaction and subjective well-being. Traditionally, studies on herd health economics have focussed on financial methods to measure the value of technical outcomes from suggested changes in management, following the basic assumption that farmers strive to maximise profit. Farmers, however, may be motivated by very different activities, e.g. animal health and welfare or other farmers' recognition, making it impossible to provide 'one-size-fts-all' consultancy because the best decision depends heavily on the internal logic and context-bound reality on each dairy farm. Relevant information may be available, but to be implemented at farm level it has to be communicated effectively. This requires a trustworthy communicator. Consequently, veterinarians are recommended to receive training in communication; keywords in this process are dialogue and reflection. An educational framework based on science and the authors' experience is presented. The aim is to guide practising cattle veterinarians into a personal learning process considered necessary for them to be recognised by farmers as trustworthy dairy herd health advisors.