Identification of Inequalities in the Selection of Liver Surgery for Colorectal Liver Metastases in Sweden.

BACKGROUND:: Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. MATERIAL AND METHODS:: Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. RESULTS:: Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p < 0.0001). Patients with liver metastases from rectal cancer (p < 0.0001) and men more often underwent liver resection (p = 0.006). A difference was found between health-care regions for the frequency of liver surgery (p < 0.0001). Patients >70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. CONCLUSION:: Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the low referral rate. The proximity to a hepatobiliary unit seems important to enhance the patient's chances of being offered liver surgery.

Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans: Short to mid-term results.

INTRODUCTION: A single-center nonrandomized clinical trial was performed to assess the safety and efficacy of IRE ablation of liver tumors in humans. METHODS: 38 malignant liver tumors on 30 patients were treated with IRE between September 2011 and September 2014. Treatment was with curative intent, and the diagnoses were colorectal cancer with liver metastases (CRLM) (n = 23), hepatocellular carcinoma (HCC) (n = 8) and other metastasis (n = 7). Patients were selected when surgery, radiofrequency ablation (RFA) or microwave ablation (MWA) was not an option, and when they met inclusion criteria (tumor size < 3 cm, 1-2 tumors). Patients were followed-up at 1 and 6 months with a contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound (CE-US) at 3 months. RESULTS: Ablation success was defined as no evidence of residual tumor in the ablated area as confirmed by CE-CT and CE-US. At 3 months ablation success was 78.9%, and 65.8% at 6 months. There was no statistically significant difference between tumor volume (<5 cm3 vs >5 cm3, p = 0.518), and between diagnosis (CRLM vs HCC, p = 0.084) in terms of local recurrence. Complications were classified according to the standardized grading system of Society of Interventional Radiology (SIR). A minor complication occurred in six patients (20%), one patient (3.3%) suffered from a major complication (bile duct dilatation and stricture of the portal vein and bile duct). No mortalities occurred at 30 days. CONCLUSIONS: IRE appears to be a safe treatment modality for a selected group of patients with liver tumors and offers high local tumor control at 3 and 6 months.

Selection for surgery and survival of synchronous colorectal liver metastases; a nationwide study.

BACKGROUND: Resection of colorectal liver metastases (CRLM) is associated with improved survival but we currently have limited population-based data on selection for surgery. METHODS: Patients in the Swedish Colorectal Cancer Register reported with liver metastases at diagnosis in 2007-2011 were identified. Clinical characteristics including American Society of Anesthesiologists classification, type of hospital and health care region were retrieved. Linkage to the National Patient Register and Statistics Sweden provided information on liver resection and socioeconomic variables. RESULTS: Synchronous CRLM was found in 4243/27,990 (15.2%) patients, of whom 1094 (25.8%) also had concurrent lung metastases. Of 3149 patients with liver-only metastases, 556 (17.8%) were subjected to liver resection. The resection rate varied by subsite; right-sided 11.7%, left-sided 19.7% and rectal cancer 22.7% (p = 0.001). It varied by type of hospital 14.1-23.6%, by region 11.5-22.7%, and was 19.8% in men and 14.9% in women (all p < 0.001). The adjusted odds were 0.74 (0.59-0.93) for females, 0.58 (0.46-0.74) for general district and 0.50 (0.37-0.68) for district hospital patients, and there were large regional differences. Patients >75 years were very unlikely to receive liver surgery 0.22 (0.15-0.32). In patients subjected to liver surgery, median survival was 57 months, 5-year survival rate was 45.4%, and those with left-sided colon cancer had the best outcome (48.8%; p = 0.02). Five-year hazard ratio for patients not subjected to liver surgery was 4.3 (3.7-5.0). CONCLUSION: Nationwide outcome after resection of synchronous CRLM was impressing but ambiguous selection mechanisms and inaccessibility need to be resolved. The implications of subsite deserve further attention.

High sensitivity with color duplex sonography in thrombosis screening after ankle fracture surgery.

BACKGROUND: Phlebography is regarded as the reference standard for diagnosing asymptomatic deep vein thrombosis (DVT) in studies of thromboprophylaxis. However, technical advances with noninvasive color duplex sonography (CDS) have made this procedure an interesting alternative. OBJECTIVES: The objective of the present prospective study was to compare the sensitivity and specificity of CDS with those of phlebography. PATIENTS: The first 180 consecutive patients included in a larger randomized trial for prolonged thromboprophylaxis were subject to unilateral CDS and to phlebography after ankle fracture surgery. The patients were examined 6 weeks after surgery, all examinations being evaluated blindly. After patient drop outs and exclusions, 144 patients were left for analysis. RESULTS: Phlebography and CDS examinations were inconclusive or were not completed for 19% of these patients (28/144). DVT was diagnosed by phlebography in 21% (24/116) of the remaining patients. Most of the thrombi were isolated calf DVTs (18/24). In contrast, DVT was diagnosed by CDS in 31% of these patients (36/116): only one case diagnosed by phlebography was missed by CDS. The specificity of CDS is thus 86% and its sensitivity is 96%. The positive predictive value is 64%, and the negative predictive value is 99%. CONCLUSIONS: CDS is a safe method for detecting asymptomatic distal DVT. It has a high sensitivity and high negative predictive value, which means that the method is highly reliable to rule out DVT. Our results indicate that CDS could be considered as an alternative method for DVT screening.

Metabolic regulation of nitrogen fixation in Rhodospirillum rubrum.

Nitrogenase activity in Rhodospirillum rubrum is post-translationally regulated by DRAG (dinitrogenase reductase glycohydrolase) and DRAT (dinitrogenase reductase ADP-ribosylation transferase). When a sudden increase in fixed nitrogen concentration or energy depletion is sensed by the cells, DRAG is inactivated and DRAT activated. We propose that the regulation of DRAG is dependent on its location in the cell and the presence of an ammonium-sensing protein.

Recurrent varicose veins: incidence, risk factors and groin anatomy.

OBJECTIVES: To investigate the recurrence rate after sapheno-femoral junction (SFJ) ligation and great saphenous vein (GSV) stripping for varicose veins (VV), to evaluate risk factors for recurrence and to classify the anatomy of the recurrence in the groin. Design. Clinical follow-up study. METHODS: Eighty-nine consecutive patients with 100 operated legs were re-examined clinically and with duplex after 6-10 years. Fourteen groins were re-explored, 13 after varicography. The anatomy in the groin was classified according to the Edinburgh system. The original medical records were examined to check for risk factors which could lead to a recurrence. RESULTS: Fifty-seven legs had incompetent veins in the groin according to duplex. In 54 of them, it was possible to define whether the incompetent veins emanated from the former SFJ. Varicography and operative findings correlated well to duplex. The main difficulty was to distinguish neovascularization from residual branches. No significant risk factor for recurrence was found in the medical records. CONCLUSIONS: Recurrence of VV after SFJ ligation is common irrespective of perioperative difficulties or the surgeon's experience. The anatomy of recurrence in the groin is difficult to classify according to the Edinburgh system mainly because neovascularization is difficult to verify.

A 16-year haemodynamic follow-up of women with pregnancy-related medically treated iliofemoral deep venous thrombosis.

OBJECTIVES: to evaluate clinical and functional long-term outcomes following pregnancy-related medically treated iliofemoral deep venous thrombosis (DVT). DESIGN: retrospective follow-up of patients identified through a registry search. MATERIAL AND METHODS: twenty-five women underwent clinical examination, colour duplex ultrasound and computerised strain-gauge plethysmography on two occasions a mean of nine and 16 years after DVT. RESULTS: 40% of the patients were completely asymptomatic and 52% had no clinical signs of venous disease after a mean follow-up of 16 years. The clinical signs were in general mild, and none of the 25 patients had skin changes or ulcers. Deep venous reflux was found in 36% of the patients; the same percentage at nine- and 16-years follow-up, and 24% had normal ultrasonographic appearance of all deep veins. None of the patients had plethysmographic evidence of outflow obstruction. There was a significant relationship between measures of venous reflux and the presence of leg swelling, but there was no clear relation between functional abnormalities and the extent of the initial DVT. CONCLUSION: even after 16 years there are relatively mild symptoms and signs of venous disease in women with medically treated pregnancy-related iliofemoral DVT. Our results do not support earlier stated opinions that these patients represent a particular risk group for developing post-thrombotic syndrome.

Balance assessment in patients with peripheral arthritis: applicability and reliability of some clinical assessments.

BACKGROUND AND PURPOSE: Many individuals with peripheral arthritis blame decreased balance as a reason for limiting their physical activity. It is therefore important to assess and improve their balance. The purpose of the present study was to evaluate the applicability and the reliability of some clinical balance assessment methods for people with arthritis and various degrees of disability. METHOD: To examine the applicability and reliability of balance tests, 65, 19 and 22 patients, respectively, with peripheral arthritis participated in sub-studies investigating the applicability, inter-rater reliability and test-retest stability of the following methods: walking on a soft surface, walking backwards, walking in a figure-of-eight, the balance sub-scale of the Index of Muscle Function (IMF), the Timed Up and Go (TUG) test and the Berg balance scale. RESULTS: For patients with moderate disability walking in a figure-of-eight was found to be the most discriminative test, whereas ceiling effects were found for the Berg balance scale. Patients with severe disability were generally able to perform the TUG test and the Berg Balance Scale without ceiling effects. Inter-rater reliability was moderate to high and test-retest stability was satisfactory for all methods assessed. CONCLUSIONS: Applicable and reliable assessment methods of clinical balance were identified for individuals with moderate and severe disability, whereas more discriminative tests need to be developed for those with limited disability.

Radioiodine treatment of hyperthyroidism in a pregnant women.

UNLABELLED: We describe the effects of radioiodine treatment of a pregnant thyrotoxic woman. METHODS: The woman received 500 MBq of (131)I in her 20th gestational week. The pregnancy was discovered 10 days after radioiodine administration. A gamma camera examination of the abdomen at that time showed a distinct focus of activity, which was interpreted as the fetal thyroid. Gamma camera examinations of the mother and fetus were performed at 10, 11, 12, 13 and 18 days after administration of the therapeutic activity and were the basis of dose calculations. The child was examined by hormone tests and mental performance tests, up to 8 yr after birth. RESULTS: The uptake at 24 hr postadministration was calculated to be 10 MBq (2%) in the fetal thyroid gland. The effective half-life was 2.5 days, giving a calculated absorbed dose to the fetal thyroid gland of 600 Gy, which is considered to be an ablative dose. The calculated absorbed dose to the fetal body, including brain, was about 100 mGy, and 40 mGy to the fetal gonads. Doses were estimated taking contributions from radioiodine in the mother, the fetal body and the fetal thyroid into consideration. The woman was encouraged to continue her pregnancy and received levothyroxine in a dose to render her slightly thyrotoxic. At full term, an apparently healthy boy, having markedly raised cord blood serum thyroid-stimulating hormone concentration and subnormal thyroxine (T4) and low-normal triiodothyronine (T3) concentrations, was born. Treatment with thyroxine was initiated from the age of 14 days, when the somatosensoric evoked potential latency time increased to a pathological value and hormonal laboratory tests repeatedly confirmed the hypothyroid state. At 8 yr of age, the child attends regular school. A neuropsychological pediatric examination showed that the mental performance was within normal limits, but with an uneven profile. He has a low attention score and displays evidently subnormal capacity regarding figurative memory. CONCLUSION: Radioiodine treatment in pregnancy in the 20th gestational week does not give a total absorbed dose to the fetal body that justifies termination of pregnancy. A high absorbed dose to the fetal thyroid, however, should be the basis of the management of the pregnancy and offspring.

Dinitrogenase reductase-activating glycohydrolase can be released from chromatophores of Rhodospirillum rubrum by treatment with MgGDP.

Dinitrogenase reductase-activating glycohydrolase (DRAG), involved in the regulation of nitrogenase activity in Rhodospirillum rubrum, is associated with chromatophore membranes in cell extracts. We show that DRAG can be specifically released by treatment with MgGDP; other nucleotides studied had no effect. The DRAG activity released corresponds to the release of DRAG protein.

Smokeless tobacco use and atherosclerosis: an ultrasonographic investigation of carotid intima media thickness in healthy middle-aged men.

There is well-documented evidence of accelerated atherosclerosis in smokers but the mechanisms still remain unclear. The relationship to the use of smokeless tobacco, involving high exposure to nicotine, have not been evaluated before. The possible role of nicotine was investigated in a clinical study of the intima media thickness in the carotid artery of 143 healthy, middle-aged men (35-60 years old) with different tobacco consumption habits. B-mode ultrasonography was performed and biochemical risk factors for cardiovascular disease (serum lipids, serum lipoproteins and plasma fibrinogen) were determined. Long term smokeless tobacco users (n = 28) did not differ significantly from never-users (n = 40) regarding bulb intima media thickness (0.80 +/- 0.13 versus 0.78 +/- 0.12 mm) or common carotid intima media thickness (0.67 +/- 0.11 versus 0.68 +/- 0.11 mm), whereas smokers (n = 29) had significantly increased wall measurements (bulb 0.87 +/- 0.19, P = 0.002 common carotid 0.74 +/- 0.13, P = 0.03) compared to never-users. Only in smokers were biochemical risk factors significantly altered towards an elevated risk. Significant effects of interaction of smoking and increased s-cholesterol levels on carotid intima media thickness were also found. Smokeless tobacco users showed similar tendencies, but without definite statistical significance. On the basis of these data, it appears most likely that the increased occurrence of atherosclerosis in smokers is caused by other components of tobacco smoke than nicotine.

Long-term use of smokeless tobacco and physical performance in middle-aged men.

To determine the influence of prolonged nicotine exposure on maximal physical working capacity, a study of clinical measures of physical fitness and cardiovascular response to exercise was performed in 144 healthy men, 35-60 years old, subdivided into smokeless tobacco users, smokers and non-users of tobacco. Regular users of smokeless tobacco, with exposures of more than 20 years, showed similar maximal oxygen uptake (mean 3.48 L min-1, SD 0.49, n = 48) to non-users (mean 3.51 L min-1, SD 0.51, n = 65). In smokeless tobacco users, higher blood pressure and heart rate values were observed at rest and at submaximal work, after exposure to tobacco shortly before the exercise test, but not at maximal work. However, significantly lower maximal oxygen uptake was found for smokers (mean 2.88 L min-1, SD 0.49, n = 31) compared with non-users (P < 0.001). Plasma concentration of continine, the main metabolite of nicotine, was significantly higher in smokeless tobacco users (mean 347 ng mL-1, SD 175, n = 48) than in smokers (mean 253 ng mL-1, SD 153, n = 31, P < 0.001). The findings indicate that long-term use of smokeless tobacco does not significantly influence exercise capacity in healthy, physically well-trained subjects.

The role of NAD+ as a signal during nitrogenase switch-off in Rhodospirillum rubrum.

The role of NAD+ in the metabolic regulation of nitrogenase, the 'switch-off' effect, in Rhodospirillum rubrum has been studied. We now show that the decrease in nitrogenase activity upon addition of NAD+ to R. rubrum is due to modification of dinitrogenase reductase. There was no effect when NAD+ was added to a mutant of R. rubrum devoid of dinitrogenase reductase ADP-ribosyltransferase, indicating that NAD+ 'switch-off' is an effect of the same regulatory system as ammonium 'switch-off'. We also show that oxaloacetate and alpha-ketoglutarate function as 'switch-off' effectors. On the other hand beta-hydroxybutyrate has the opposite effect by shortening the 'switch-off' period. Furthermore, by using an inhibitor of glutamate synthase the role of this enzyme in 'switch-off' was investigated. The results are discussed in relation to our proposal that changes in the concentration of NAD+ are involved in initiating 'switch-off'.

Changes in the NAD(P)H concentration caused by addition of nitrogenase 'switch-off' effectors in Rhodospirillum rubrum G-9, as measured by fluorescence.

The effect of nitrogenase 'switch-off' effectors on the concentration of NAD(P)H in Rhodospirillum rubrum G-9 was investigated by fluorescence. A rapid decrease in fluorescence was observed when cells, either N2-grown or nitrogen-starved, were subjected to the effectors, but not when sodium chloride or Tris buffer was added. No effects on the fluorescence were observed in non-nitrogen fixing cultures except when NAD+ was added. The results strongly indicate that the redox state of the pyridine nucleotide pool affects the control of the regulation of nitrogenase activity in R. rubrum.

Radionuclide mobility and bioavailability in Norwegian and Soviet soils.

A sequential extraction procedure has been applied to study the speciation of Chernobyl-derived radionuclides (137Cs and 90Sr) in soils from Norway, and from Byelorussia and the Chernobyl region in the USSR. Most 137Cs (greater than 80%) was strongly associated with soil components, whereas 90Sr was more mobile, up to 70% being found in the easily extractable fractions. The 90Sr: 137Cs ratio decreased with the distance from the reactor, reflecting the higher proportion of hot particles deposited in the regions close to the reactor, and the easily extractable fraction of 90Sr was significantly lower in the soils collected from the Chernobyl area. The distribution of stable Cs and stable Sr in the extraction fractions was similar for the various sites. Therefore, the location-specific differences in the distribution of 90Sr and, to a lesser extent, 137Cs arise because of fallout speciation rather than because of local environmental factors.

Degenerative joint disease in ballet dancers.

Forty-four retired dancers were studied with regard to degenerative joint disease in the lower limbs. Six cases of coxarthrosis were found, significantly more than expected in the general population. In addition, there were four cases of tibio-femoral arthrosis, six of knee osteophytosis, four of patellofemoral arthrosis, three of chondrocalcinosis, and one of bilateral ankle arthrosis. More than one-half of the dancers had arthrosis in the metatarsophalangeal joints.