Akademiska Barnsjukhuset

OBJECTIVE: To investigate the efficacy of preoperative short-term radiotherapy in patients with mobile rectal cancer undergoing total mesorectal excision (TME) surgery. SUMMARY BACKGROUND DATA: Local recurrence is a major problem in rectal cancer treatment. Preoperative short-term radiotherapy has shown to improve local control and survival in combination with conventional surgery. The TME trial investigated the value of this regimen in combination with total mesorectal excision. Long-term results are reported after a median follow-up of 6 years. METHODS: One thousand eight hundred and sixty-one patients with resectable rectal cancer were randomized between TME preceded by 5 x 5 Gy or TME alone. No chemotherapy was allowed. There was no age limit. Surgery, radiotherapy, and pathologic examination were standardized. Primary endpoint was local control. RESULTS: Median follow-up of surviving patients was 6.1 year. Five-year local recurrence risk of patients undergoing a macroscopically complete local resection was 5.6% in case of preoperative radiotherapy compared with 10.9% in patients undergoing TME alone (P < 0.001). Overall survival at 5 years was 64.2% and 63.5%, respectively (P = 0.902). Subgroup analyses showed significant effect of radiotherapy in reducing local recurrence risk for patients with nodal involvement, for patients with lesions between 5 and 10 cm from the anal verge, and for patients with uninvolved circumferential resection margins. CONCLUSIONS: With increasing follow-up, there is a persisting overall effect of preoperative short-term radiotherapy on local control in patients with clinically resectable rectal cancer. However, there is no effect on overall survival. Since survival is mainly determined by distant metastases, efforts should be directed towards preventing systemic disease.

W. EUGENE BROADHEAD, BERTON H. KAPLAN, SHERMAN A. JAMES, EDWARD H. WAGNER, VICTOR J. SCHOENBACH, ROGER GRIMSON, SIEGFRIED HEYDEN, GŌSTA TIBBLIN, STEPHEN H. GEHL

AIM: To reach consensus among specialists from the Nordic countries on the present state-of-the-art in treatment of undescended testicles. METHODS: A group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for two days. Before the meeting, reviews of the literature had been prepared by the participants. RECOMMENDATIONS: The group came to the following unanimous conclusions: (1) In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long term adverse effects on spermatogenesis. Thus, surgery is to be preferred. (2) Orchiopexy should be done between 6 and 12 months of age, or upon diagnosis, if that occurs later. (3) Orchiopexy before age one year should only be done at centres with both paediatric surgeons/urologists and paediatric anaesthesiologists. (4) If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery--to paediatric rather than general surgeons/urologists if the boy is less than one year old or if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

In fresh-frozen amputated- and cadaver arm specimens the anatomy and stability of the distal radio ulnar joint were investigated. The articulating surface of the sigmoid notch of the radius and the corresponding surface of the ulnar head facing the sigmoid notch were studied in transverse cryo sections. In each specimen the radius of the curvature of the sigmoid notch was 4-7 mm larger than that of the ulnar head and consequently pronation and supination are combined rotation-sliding movement in the distal radio ulnar joint. The radio ulnar ligament consists of a dorsal and a volar fibrous part, broadly attached to the distal rim of the sigmoid notch and converging towards the fovea of the ulnar head. The cartilaginous disc is centrally located between these fibrous strands. In neutral position the articulating surface of the sigmoid notch is optimally covering the articulating surface of the ulnar head. This contact area is gradually diminished during pronation-supination until only a marginal contact remains at the end of each movement. The distal radius is kept stable in pronation by the volar part and in supination by the dorsal part of the radio ulnar ligament.

Antibodies to cholinergic receptor structures were found in 75% of 76 Finnish and 93% of 175 Swedish patients with myasthenia gravis. The amount of antibodies showed a positive correlation to the severity of the disease, and was reduced during immunosuppressive treatment, and by thymectomy. Thymoma patients had high values. The antibody was also found in the cerebrospinal fluid. Two healthy newborn babies of myasthenic mothers had antibodies during the first weeks of life, in spite of no clinical symptoms. The occurrence of IgM antibodies before IgM antibodies in two patients during the early stages of myasthenia gravis suggests that the antibody is not a primary cause of the disease.

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.

The "sick building syndrome" involves symptoms such as eye, skin and upper airway irritation, headache, and fatigue. A multifactorial study was performed among personnel in consecutive cases of sick buildings to investigate relationships between such symptoms, exposure to environmental factors, and personal factors. The total indoor hydrocarbon concentration was significantly related to symptoms. Other indoor exposures such as room temperature, air humidity, and formaldehyde or carbon dioxide concentration did not correlate with the symptoms. Personal factors such as reported hyperreactivity and sick leave due to airway diseases were strongly related to the sick building syndrome. Other factors associated with the sick building syndrome were smoking, psychosocial factors, and experience of static electricity at work. Neither atopy, age, sex, nor outdoor exposures correlated significantly with the number of symptoms. It was concluded that the sick building syndrome is of multifactorial origin and related to both indoor hydrocarbon exposure and individual factors.

SUMMARY Serial blood volume measurements were made in 27 normal full‐term newborn infants using iodinated human albumin. At the moment of birth the newborn infant was estimated to have a blood volume of 78 ml/kg with a venous hematocrit of 48 %. When the cord‐clamping was delayed for 5 minutes the blood volume increased by 61 % to 126 ml/kg. This placental transfusion amounted to 166 ml for a 3500 g infant, one‐quarter of which occurred in the first 15 seconds, and one‐half within 60 seconds of birth. Stripping of the umbilical cord 10 times during the 5 minutes did not increase the volume of the transfusion. When the placental transfusion was prevented by immediate clamping of the cord, the blood volume did not change appreciably during the first 4 hours of life. On the other hand, there was a marked decrease in blood volume from 126 to 89 ml/kg during the first 4 hours in infants who had received a placental transfusion. This decrease was brought about by the transudation of one‐half of the original plasma volume, so that the venous hematocrit rose from 48 % at birth to 64 % by 4 hours. In all but three of the infants studied there was an increase in blood volume between 4 and 24 hours of age which was due to an increase in plasma volume averaging 22 ml per infant. There was no appreciable change in blood volume between 24 and 72 hours of age. The red cell volume remained stable during the first three days of life in each of the infants; those who had received a placental transfusion maintained a red cell volume about 60 % larger than those who had not. At 72 hours of age the blood volume had stabilized after the plasma shifts of the first day of life, and the range of values extended from 75 to 107 ml/kg. This variation between individuals was due in large part to differences in hematocrit which ranged from 39 % to 67 %, and these in turn were related to the volume of placental transfusion. Average values at 72 hours for infants who had received no placental transfusion were 82 ml/kg blood volume, 31 ml/kg red blood cell volume, 51 ml/kg plasma volume, and 44 % venous hematocrit. For infants who had received a placental transfusion they were 93 ml/kg blood volume, 49 ml/kg red blood cell volume, 44 ml/kg plasma volume, and 60 % venous hematocrit.

Microelectrode recordings were made in peroneal muscle nerve fascicles in 9 patients with traumatic spinal cord lesions at the C5 to T8 level. In 4 patients the lesion was incomplete with some sensibility but no voluntary motor function below the level of the lesion. All patients had increased tendon jerks. EMG was recorded in 5 patients and showed signs of some peripheral denervation. Simultaneous recordings from nerves to skin and to muscle were made in 2 patients and control recordings were made in 19 normal subjects. In the patients, spontaneous neural activity was sparse but after a latency of 0.5-1.1 s strong mechanical and electrical stimuli applied to the skin below the level of the lesion, stimulation of the urinary bladder and deep breaths induced bursts of efferent impulses with a conduction velocity of 0.65 m X s-1. The discharges were often followed by cutaneous vasoconstriction and/or reduction of skin resistance. It is concluded that the neural bursts contained sympathetic impulses of spinal origin. The main differences between patients and normal subjects were spontaneous muscle sympathetic activity was much lower in the patients; no evidence of arterial baroreflex modulation of muscle sympathetic activity was obtained in the patients; and in the patients a given stimulus induced sympathetic reflex discharges which occurred synchronously in muscle and skin nerve branches. Increases of intravesical pressure induced only weak increases of muscle sympathetic activity in the patients but nevertheless marked hypertensive reactions occurred. It is suggested that the excitability of decentralized spinal sympathetic neurons to muscles is usually decreased and that mechanisms other than exaggerated sympathetic outflow must be important for evoking episodes of high blood pressure in patients with spinal cord injuries.

The aim of this study was to investigate whether asthma is associated with decreased quality of sleep and increased daytime sleepiness. The study involved a random population of 2,202 subjects supplemented by 459 subjects with suspected asthma, aged 20-45 yrs. The subjects were from Reykjavik (Iceland), Uppsala and Göteborg (Sweden) and Antwerp (Belgium), and participated in the European Community Respiratory Health Survey. The investigation included a structured interview, methacholine challenge, skinprick tests and a questionnaire on sleep disturbances. Participants in Iceland and Sweden also estimated their sleep times and made peak expiratory flow (PEF) recordings during a period of 1 week. Asthma was defined as self-reported physician-diagnosed asthma with current asthma-related symptoms (n = 267). Difficulties inducing sleep (DIS) and early morning awakenings (EMA) were about twice as common, and daytime sleepiness 50% more common, in asthmatics compared with subjects without asthma. After adjusting for possible confounders, a positive association was found between asthma and: DIS (odds ratio (OR) = 1.8); EMA (OR = 2.0); daytime sleepiness (OR = 1.6); snoring (OR = 1.7); and self reported apnoeas (OR = 3.7). Allergic rhinitis, which was reported by 71% of subjects with asthma, was independently related to DIS (OR = 2.0) and daytime sleepiness (OR = 1.3). A significant correlation was found between the number of asthma-related symptoms and sleep disturbances (p < 0.001). Asthma is associated with decreased subjective quality of sleep and increased daytime sleepiness. Concurrent allergic rhinitis may be an important underlying cause of sleep impairment in asthmatic patients.

A phantom study was performed to assess the accuracy of MRI in volume determination of pituitary macroadenomas, using the summation of areas technique. Five phantoms, 3-4 cm in diameter, simulating pituitary macroadenomas of various shapes, were evaluated. The volume could adequately and reproducibly be determined, regardless of minor rotational variations of the phantom position. Using a three-dimensional SE sequence with 2.5 mm slices, the error was independent of the shape of the phantom and did not differ significantly from zero (less than 5%); this sequence was found to be the best of those tested. The coefficient of variation between examinations with different tilts was 2%. In a clinical part, the volume of pituitary macroadenomas was determined with the same technique on coronal two-dimensional 5 mm images and was used as a "gold standard" to which the largest transverse, sagittal, vertical, and oblique diameters, a central tumor area, and the product of the three orthogonal diameters were correlated. In interpatient comparisons the largest diameter was found to be useful, but only as a rough measure of the tumor size. The formula 0.5 x width x length x height provided a fairly adequate estimation of the tumor volume, except in the largest tumors. In intrapatient comparisons during bromocriptine treatment, the height was found to be the best of the diameters, but the central tumor area or the product of the orthogonal diameters was preferable.

The pathogenesis of the late post-traumatic rupture of the extensor pollicis longus tendon has never been satisfactorily explained. In the present series of fifty-nine ruptures two were partial, making possible an exact localization of the rupture. Microangiographic studies performed on amputated arms showed that this part of the tendon was poorly vascularized. Our study confirms earlier observations that ruptures most commonly occur after undisplaced fractures. It is suggested that increased pressure within the non-ruptured tendon sheath jeopardizes the blood flow in the already poorly vascularized parts of the tendon, leading to degeneration and rupture, usually within eight weeks. An haematoma inside the sheath interfering with the production of synovial fluid, could deprive the tendon of an alternative nutrition via diffusional pathways.

[Reliability of the hospital registry : The diagnostic data are better than their reputation]

BACKGROUND: Long-term pain is an important outcome after inguinal hernia repair. The aim of this study was to test the validity and reliability of a specific Inguinal Pain Questionnaire (IPQ). METHODS: The study recruited patients aged between 15 and 85 years who had undergone primary inguinal or femoral hernia repair. To test the validity of the questionnaire, 100 patients received the IPQ and the Brief Pain Inventory (BPI) 1 and 4 weeks after surgery (group 1). To test reliability and internal consistency, 100 patients received the IPQ on two occasions 1 month apart, 3 years after surgery (group 2). Non-surgery-related pain was analysed in group 3 (2853 patients). RESULTS: A significant decrease in IPQ-rated pain intensity was observed in the first 4 weeks after surgery (P < 0.001). Significant correlations with corresponding BPI pain intensity items corroborated the criterion validity (P < 0.050). Logical incoherence did not exceed 5.5 per cent for any item. Values for kappa in the test-retest in group 2 were higher than 0.5 for all but three items. Cronbach's alpha was 0.83 for questions on pain intensity and 0.74 for interference with daily activities. CONCLUSION: This study found good validity and reliability for the IPQ, making it a useful instrument for assessing pain following groin hernia repair.

Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.

BACKGROUND: Injuries are a leading cause of death in the young. Of transfused patients in Sweden about 10% have injuries and 2% receive plasma and 0,2% platelets. Quality, safety, sufficiency and the optimal use of blood and blood components have been the focus for the Council of Europe since 1955 and Guidelines are published. In 2002 the European Community adopted the Directive 2002/98/EC with legally binding requirements for the quality and safety of blood and blood components, including hemovigilance systems. THE USE OF BLOOD COMPONENTS: Data on the use of blood components are regularly collected by the Council of Europe. The use per 1,000 inhabitants show wide variations. THE RISKS OF TRANSFUSION: The potential adverse effects of plasma and platelet components, listed in recently published monographs from the Council of Europe, have been compared with published data from hemovigilance systems. There are two principally different hemovigilance systems in Europe, and the reported overall rates show a fifty-fold difference. Severe transfusion reactions are rare or very rare. Transfusion related acute lung injury (TRALI) and sepsis due to inadvertent bacterial contamination are probably of particular inportance for trauma patients. These reactions are presumably insufficiently recognized and reported. CONCLUSION: Common definitions and systems for hemovigilance will be important for the evaluation of new safety measures. A commonly accepted definition of TRALI will aid in the differential diagnosis of transfusion reactions. Measures to further reduce the rate of transfusion reactions will render the risk-benefit ratio of appropiate transfusions more favorable.

BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 and ALL-2000 protocols. Fifty-five TRDs were identified among the 1,645 ALL-92 patients and 33 among the 1,090 ALL-2000 patients. RESULTS: There was no significant difference in the incidence of TRDs between the two protocols (3.4% vs. 3.2%). Five patients died before initiation of therapy (0.2%), and the overall subsequent risk of induction death and death in first complete remission (CR1) was 1.2% and 1.8%, respectively. Infections were the major cause of death comprising 72% of all cases including 9 deaths from Pseudomonas aeruginosa and 11 deaths from fungal infections. Other causes of death included bleeding or thrombosis (eight patients), tumour burden related toxicities (seven patients) and organ toxicity (seven patients). Female gender (hazard ratio (HR): 2.2, 95% confidence interval (95% CI): 1.4-3.4), high white blood cell count (≥ 200 × 10(9) /L) at diagnosis (HR: 3.5, 95% CI: 1.7-7.1), T-cell disease (HR: 1.9, 95% CI: 1.01-3.7), Down syndrome (HR: 7.3, 95% CI: 3.6-14.9) and haematopoietic stem cell transplantation in CR1 (HR: 8.0, 95% CI: 3.3-19.5) were identified as independent risk factors for TRD. CONCLUSION: Several TRDs were potentially preventable and future efforts should be directed towards patients at risk.

A preliminary report is given of some studies concerning Imcterial vaccines in arthmatic children. A method is introduced in which nasal eosinophilia is studied in connection with local applications of bacterial vaccines and controls. A reproducable positive response is found in three patients of a selected group suffering from pmumed “bacterial allergy”. In two of these patients focal mthmatir reactions are observed following the injection of minute doses of the vaccine in question. The method is briefly discussed.

OBJECTIVE: To study the long-term outcome after treatment with uvulopalatopharyngoplasty (UPPP). DESIGN: Long-term follow-up (4-8 years) with polysomnography. SETTING: Referral center for patients with sleep-disordered breathing. PATIENTS: Thirty-four consecutive patients of whom 25 (22 men and 3 women; mean age, 49 years) participated in the follow-up. All patients had obstructive sleep apnea syndrome. INTERVENTION: Uvulopalatopharyngoplasty. MAIN OUTCOME MEASURES: Symptoms and apnea-hypopnea index (AHI) before and after UPPP. Response to treatment defined as a 50% or more reduction in AHI and a postoperative AHI of 10 or less. RESULTS: Reduced prevalence of snoring and daytime sleepiness and reduction in AHI (mean [+/-SD], 40 +/- 26 to 21 +/- 21) at follow-up (P < .001). Sixteen patients (64%) were responders after 6 months and 12 (48%) at the long-term follow-up. Responders had a lower preoperative AHI (25 +/- 7) than did nonresponders (48 +/- 29) (P < .05). None of the 7 patients with preoperative AHI of more than 40 were responders (P < .01). No difference was seen in preoperative body mass index, lung function, ventilatory response to carbon dioxide, computed tomography scan of upper airways, or change in body mass index between responders and nonresponders. CONCLUSIONS: Four to 8 years after UPPP, about half of our patients were clinically and objectively improved. Uvulopalatopharyngoplasty should be reserved for patients with mild or moderate obstructive sleep apnea. After UPPP, long-term follow-up is recommended because some initially successfully treated patients will relapse in the long term.

There is evidence of poor prognosis in women with pregnancy-associated breast cancer (PABC) diagnosed during pregnancy or within 2 years of delivery. Using a large, population-based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15-44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi-Generation Register. Age-standardized distributions of tumor stage (tumor size, nodal status, metastasis), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years postdelivery. Adjusted hazard ratios for all-cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year postdelivery) and 3,598 during 2-10 years postdelivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0-12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple-negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and nonsignificant. The poorer prognosis observed in women with PABC appears to be largely explained by more adverse tumor characteristics at diagnosis.