Search

Background: Postpartum haemorrhage is one of the leading causes of maternal mortality in low-income countries. Improving health workers' competencies in obstetric emergencies in low-income settings, has been recognized as an important factor in preventing maternal mortality and morbidity. mHealth interventions in maternal and newborn health care has shown the potential to improve health service delivery. Strong study designs such as randomized controlled trials are missing to estimate the effectiveness of the mHealth interventions., Methods: Between August 2013 and August 2014, 70 health facilities in West Wollega Region, Ethiopia were included and randomized to intervention or control in a cluster randomized controlled trial. At intervention facilities birth attendants were provided with a smartphone with the SDA installed. Of 176 midwives and "health extension workers," 130 completed at 12 months follow-up. At baseline and after 6- and 12-months participants were assessed. Knowledge was tested by a Key Feature Questionnaire, skills by an Objective Structured Assessment of Technical Skills in a structured role-play scenario., Results: Baseline skills scores were low and comparable with a median of 12/100 in the intervention and the control group. After 6 months skills had doubled in the intervention group (adjusted mean difference 29.6; 95% CI 24.2-35.1 compared to 1·8; 95% CI - 2.7 to 6.3 in the control group). At 12 months skills had further improved in the intervention group (adjusted mean difference 13.3; 95% CI 8.3-18.3 compared to 3.1; 95% CI - 1.0 to 7.3 in the control group). Knowledge scores also significantly improved in the intervention group compared to the control (adjusted mean difference after 12 months 8.5; 95% CI 2.0-15.0)., Conclusion: The Safe Delivery App more than doubled clinical skills for managing postpartum haemorrhage among birth attendants making it an attractive tool to reduce maternal mortality., Trial Registration: Clinicaltrial.gov Identifier NCT01945931. September 5, 2013., (© 2023. The Author(s).)

Background: Healthcare associated infections is a global burden and is one of the main causes of maternal and neonatal morbidity and mortality during the time of labour when admitted to the hospital. Healthcare workers' hands are in most cases the vehicle for transmission of microorganisms from patient to patient. Good hand hygiene practices at the bedside are a simple way of reducing healthcare associated infections. The objective was to assess the impact of a criterion-based audit on infection prevention performance and knowledge during vaginal delivery at a hospital in Tanzania. The quantitative findings were discussed with staff to identify barriers and solutions to quality improvement., Methods: A mixed-method uncontrolled, before and after intervention study by criterion-based audit was performed at the labour ward at Kilimanjaro Christian Medical Centre. Criteria for best practice were established together with key staff based on national and international guidelines. Sixty clean procedures during vaginal birth were observed and assessed by a structured checklist based on the audit criteria. Baseline findings were discussed with staff and an intervention performed including a short training and preparation of alcohol-based hand rub. Hereafter another 60 clean procedures were observed, and performance compared to the care before the intervention. Furthermore, a knowledge test was performed before and after the intervention., Results: Hand washing increased significantly after a procedure from 46.7% to 80% (RR=1.71 95% CI; 1.27 to 2.31), the use of alcohol-based hand rub before a procedure from 1.7% to 33.3% p < .001 ), and the use of alcohol-based hand rub after procedure from 0% to 30% p < .00l ). After the intervention the mean score for the knowledge test increased insignificantly from 59.3% to 65.3%, (mean difference = 6.1%, 95% CI; -4.69 to 16.88)., Conclusion: The criterion-based audit process identified substandard care for infection prevention at the labour ward. An intervention of discussing baseline findings and a short training session and introducing alcohol-based hand rub resulted in improvements on infection prevention performance., Competing Interests: Competing Interests None declared., (© The East African Health Research Commission 2021.)

Background: Health workers in many low-income countries are not adequately trained to deliver pregnant women safely. In response to this, the Safe Delivery App (SDA) has been developed, which provides animated clinical instruction videos in basic emergency obstetric and neonatal care. The SDA aims to improve knowledge and skills of health workers located in the periphery of the health system in order to improve quality of care and potentially save the lives of mothers and newborns. The objective of this qualitative study was to explore the users' experiences with using the SDA and in which ways the SDA influences their work situation and their perceived ability to conduct safe deliveries., Methods: Eleven focus group discussions and four individual interviews were conducted with a total of 56 midwives, nurses and health extension workers from five districts in West Wollega Zone, Oromiya region of Ethiopia. The data further include observations and informal conversations. All interviews were recorded, transcribed verbatim, checked for corrections and analysed using systematic text condensation., Results: The findings indicate that health workers perceive the SDA as a useful tool, which helps them memorize and update knowledge and skills, and improves their confidence. User patterns follow the relevancy of the tool to the health workers' work situation - those who conduct many deliveries have more often used the app in emergency situations, whereas those who conduct few deliveries more often use it to improve their knowledge and to provide health education to pregnant women. Thus, the SDA is used in varying ways depending on internal and external factors such as own competencies, availability of equipment and frequency of births attended. Health workers experienced that community members showed more recognition and trust in their abilities and ascribed this to their increased confidence in assisting in deliveries. The increased recognition from communities may also be associated to a medical technology., Conclusion: The health workers perceive the SDA as having improved their ability to manage complications during childbirth and have gained increased recognition and trust from the communities.

Background: Health-care-associated infection (HCAI) is a big challenge in both low- and high-income countries. Around childbirth, infection is among the main causes of maternal and perinatal morbidity and mortality. Appropriate hand hygiene practice is a simple and cost-effective way of reducing HCAIs. This study aimed to assess the baseline performance and knowledge of proper hand hygiene during caesarean sections and the impact of interventions guided by a criterion-based audit at a tertiary health facility in Tanzania., Methods: A noncontrolled, before-and-after intervention study, guided by a criterion-based audit, was carried out. A criterion based checklist was used for direct observations of hand hygiene performance during cesarean section. A self-administered questionnaire was used to assess knowledge on infection prevention. Performance was compared before and after a half-way intervention., Results: At baseline, low-quality hand hygiene performance was observed. Significant improvements of hand hygiene performance were observed for a number of criteria. Long nails: performance reduction from 15 (25%) to 3 (5%) ( P =.04), polished nails: from 11 (18%) to 1 (2%) ( P =.04), a score increase in hand wash with water from 43.8 (73%) to 60 (100%) ( P =.001). Postoperatively, correct glove removal increased from 20 (33%) to 37.8 (66%) ( P =.01). Alcohol-based hand rub use increased from 2 (3%) to 21 (35%) ( P =.001). The number of health-care workers who did not wash hands after procedure with either water or alcohol-based hand rub reduced from 35 (58%) to 10 (17%) ( P =.001). After the intervention, poor knowledge among health-care workers reduced from 7 (39%) to 3 (17%), while moderate knowledge increased from 8 (44%) to 12 (67%)., Conclusion: Feedback, discussion of findings, training, visual reminders, and distribution of alcohol-based hand rub, as part of a criterion-based audit is a powerful way of improving hand hygiene performance and knowledge in surgical wards., Competing Interests: Competing Interests: None declared., (© The East African Health Research Commission 2019.)

We present a case of persistent trophoblast tissue (PT) five weeks after salpingectomy for tubal pregnancy. The fallopian tube-sparing method (salpingotomy) has a greater risk of PT than removal of the whole fallopian tube (salpingectomy) has. A 32-year-old woman was treated with salpingectomy on suspicion of a bleeding ectopic pregnancy and was readmitted due to PT. There is no evidence for measuring the human chorionic gonadotropin (hCG) level as routine follow-up after salpingectomy, but it is important to be aware of the risk of PT and if in doubt measure the levels of hCG.

Importance: Health apps in low-income countries are emerging tools with the potential to improve quality of health care services, but few apps undergo rigorous scientific evaluation., Objective: To determine the effects of the safe delivery app (SDA) on perinatal survival and on health care workers' knowledge and skills in neonatal resuscitation., Design, Setting, and Participants: In a cluster-randomized clinical trial in 5 rural districts of Ethiopia, 73 health care facilities were randomized to the mobile phone intervention or to standard care (control). From September 1, 2013, to February 1, 2015, 3601 women in active labor were included at admission and followed up until 7 days after delivery to record perinatal mortality. Knowledge and skills in neonatal resuscitation were assessed at baseline and at 6 and 12 months after the intervention among 176 health care workers at the included facilities. Analyses were performed based on the intention-to-treat principle., Interventions: Health care workers in intervention facilities received a smartphone with the SDA. The SDA is a training tool in emergency obstetric and neonatal care that uses visual guidance in animated videos with clinical instructions for management., Main Outcomes and Measures: The primary outcome was perinatal death. Secondary outcomes included the knowledge and clinical management of neonatal resuscitation (skills) of health care workers before the intervention and after 6 and 12 months., Results: The analysis included 3601 women and 176 health care workers. Use of the SDA was associated with a nonsignificant lower perinatal mortality of 14 per 1000 births in intervention clusters compared with 23 per 1000 births in control clusters (odds ratio, 0.76; 95% CI, 0.32-1.81). The skill scores of intervention health care workers increased significantly compared with those of controls at 6 months (mean difference, 6.04; 95% CI, 4.26-7.82) and 12 months (mean difference, 8.79; 95% CI, 7.14-10.45) from baseline, corresponding to 80% and 107%, respectively, above the control level. Knowledge scores also significantly improved in the intervention compared with the control group at 6 months (mean difference, 1.67; 95% CI, 1.02-2.32) and at 12 months (mean difference, 1.54; 95% CI, 0.98-2.09), corresponding to 39% and 38%, respectively, above the control level., Conclusions and Relevance: The SDA was an effective method to improve and sustain the health care workers' knowledge and skills in neonatal resuscitation as long as 12 months after introduction. Perinatal mortality was nonsignificantly reduced after the intervention. The results are highly relevant in low-income countries, where quality of care is challenged by a lack of continuing education., Trial Registration: clinicaltrials.gov Identifier: NCT01945931.

Phosphorus is an essential mineral resource for the growth of crops and thus necessary to feed the ever increasing global population. The essentiality and irreplaceability of phosphorus in food production has raised the concerns regarding the long-term phosphorus availability and the resulting food supply issues in the future. Hence, the recovery of phosphorus from waste activated sludge and other waste streams is getting huge attention as a viable solution to tackle the potential availability issues of phosphorus in the future. This study explores the environmental implications of phosphorus recovery from waste activated sludge in Denmark and further elaborates on the potential availability or scarcity issue of phosphorus today and 2050. Life cycle assessment is used to assess the possibility of phosphorus recovery with little or no environmental impacts compared to the conventional mining. The phosphorus recovery method assessed in this study consists of drying process, and thermal gasification of the waste activated sludge followed by extraction of phosphorus from the ashes. Our results indicate that the environmental impacts of phosphorus recovery in an energy efficient process are comparable to the environmental effects from the re-use of waste activated sludge applied directly on farmland. Moreover, our findings conclude that the general recommendation according to the waste hierarchy, where re-use of the waste sludge on farmland is preferable to material and energy recovery, is wrong in this case. Especially when phosphorus is a critical resource due to its life threatening necessity, lack of substitution options and potential future supply risk originating due to the high level of global supply concentration., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Complications of unsafe abortion are a major contributor to maternal deaths in developing countries. This study aimed to evaluate the clinical assessment for life-threatening complications and the following management in women admitted with complications from abortions at a rural hospital in Uganda., Methods: A partially completed criterion-based audit was conducted comparing actual to optimal care. The audit criteria cover initial clinical assessment of vital signs and management of common severe complications such as sepsis and haemorrhage. Sepsis shall be managed by immediate evacuation of the uterus and antibiotics in relation to and after surgical management. Shock by aggressive rehydration followed by evacuation. In total 238 women admitted between January 2007 and April 2012 were included. Complications were categorized as incomplete, threatened, inevitable, missed or septic abortion and by trimester. Actual management was compared to the audit criteria and presented by descriptive statistics., Results: Fifty six per cent of the women were in second trimester. Abortion complications were distributed as follows: 53 % incomplete abortions, 28 % threatened abortions, 12 % inevitable abortions, 4 % missed abortions and 3 % septic abortions. Only one of 238 cases met all criteria of optimal clinical assessment and management. Thus, vital signs were measured in 3 %, antibiotic criteria was met in 59 % of the cases, intravenous fluid resuscitation was administered to 35 % of women with hypotension and pain was managed in 87 % of the cases. Sharp curettage was used in 69 % of those surgically evacuated and manual vacuum aspiration in 14 %. In total 3 % of the abortions were categorized as unsafe. Two of eight women with septic abortion had evacuation performed during admission-day, one woman died due to septic abortion and one from severe haemorrhage., Conclusions: Guidelines were not followed and suboptimal assessment or management was observed in all but one case. This was especially due to missing documentation of vital signs necessary to diagnose life-threatening complications, poor fluid resuscitation at signs of shock, and delayed evacuation of septic abortion.

In areas where water is a major source of dietary iodine (I), the I concentration in drinking water is an important factor for public health and epidemiological understandings. In Denmark, almost all of the drinking water is originating from groundwater. Therefore, understanding the I variation in groundwater and governing factors and processes are crucial. In this study, we perform uni- and multivariate analyses of all available historical Danish I groundwater data from 1933 to 2011 (n = 2,562) to give an overview on the I variability for first time and to discover possible geochemical associations between I and twenty other elements and parameters. Special attention is paid on the description and the quality assurance of this complex compilation of historical data. The high variability of I in Danish groundwater (

Iodine is essential for human health. Many countries have therefore introduced universal salt iodising (USI) programmes to ensure adequate intake for the populations. However, little attention has been paid to subnational differences in iodine intake from drinking water caused by naturally occurring spatial variations. To address this issue, we here present the results of a Danish nationwide study of spatial trends of iodine in drinking water and the relevance of these trends for human dietary iodine intake. The data consist of treated drinking water samples from 144 waterworks, representing approx. 45% of the groundwater abstraction for drinking water supply in Denmark. The samples were analysed for iodide, iodate, total iodine (TI) and other major and trace elements. The spatial patterns were investigated with Local Moran's I. TI ranges from <0.2 to 126 μg L(-1) (mean 14.4 μg L(-1), median 11.9 μg L(-1)). Six speciation combinations were found. Half of the samples (n = 71) contain organic iodine; all species were detected in approx. 27% of all samples. The complex spatial variation is attributed both to the geology and the groundwater treatment. TI >40 μg L(-1) originates from postglacial marine and glacial meltwater sand and from Campanian-Maastrichtian chalk aquifers. The estimated drinking water contribution to human intake varies from 0% to >100% of the WHO recommended daily iodine intake for adults and from 0% to approx. 50% for adolescents. The paper presents a new conceptual model based on the observed clustering of high or low drinking-water iodine concentrations, delimiting zones with potentially deficient, excessive or optimal iodine status. Our findings suggest that the present coarse-scale nationwide programme for monitoring the population's iodine status may not offer a sufficiently accurate picture. Local variations in drinking-water iodine should be mapped and incorporated into future adjustment of the monitoring and/or the USI programmes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The objective was to compare two teaching methods for postpartum hemorrhage management: interactive hands-on training and non-interactive video training. In a controlled intervention study at a secondary health care center in Kenya, the two training methods, based on the Advanced Life Support in Obstetrics curriculum, were evaluated utilizing structured observation of a standardized scenario before and after training. Both intervention groups significantly increased in performance scores after receiving hands-on training: 40% (95% CI 29.5-47.0) and video training: 34.5% (95% CI 25.0-42.0); likewise, pass rates improved significantly. No significant differences in performance score or pass rates were found between the two methods. The findings indicate that postpartum hemorrhage management training by mobile media might be just as effective as conventional hands-on training and a feasible way to overcome the outreach gap in sub-Saharan Africa's rural areas, where peripheral health facilities are generally difficult to reach with conventional training programs., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Metallothionein (MT) expression is considered to be a prognostic factor that promotes tumor resistance to apoptosis. In non-Hodgkin lymphomas, MT is differentially expressed and constitutes a risk factor. We have characterised MT in lymph nodes of Hodgkin lymphoma (HL) [patients with nodular sclerosis (NSHL), mixed cellularity (MCHL), lymphocyte-rich classical HL (LRCHL) and nodular lymphocyte predominant HL (NLPHL)] and in controls. MT expression is significantly and differentially altered in the HL subtypes. NSHL and MCHL show highly increased MT throughout the lymph node. In contrast, MT is barely increased in LRCHL relative to controls. NLPHL shows a distinct pattern of heterogeneous MT with increased MT in nodular areas surrounded by MT-negative tissue. The cellular MT sources are reactive, infiltrating (non-neoplastic) cells, whereas neoplastic cells are devoid of MT. We show for the first time that MT is differentially expressed in subclassified HL.

Introduction: In Denmark 650 renal cell carcinoma cases are diagnosed every year, and in 5-9% of the cases there is spread of the tumour in the form of tumour thrombosis in the inferior vena cava inferior., Aim: The purpose of this work is to describe the methods and outcome of operation regarding patients with such tumour thrombosis. According to the literature, the survival of these patients is not reduced provided there are no metastases to regional glands nor any distant metastases., Methods: We describe 13 cases operated in the urological ward at Rigshospitalet (the Danish national hospital) during a nine-year period., Results: In all 13 cases radical nephrectomy was performed and the tumour thrombus removed. In three cases the thrombus stretched into the right atrium, and the operations on these patients were performed in extra-corporal circulation. In one case the operation was performed in veno-venous bypass. There were two peri-operative deaths; one patient died during the operation from uncontrollable bleeding, the other on the ninth postoperative day. In both cases the thrombus stretched into the atrium. There were minor complications in three out of the remaining 11 cases, and in the last eight cases there were no complications. The two year survival was estimated at 50%., Conclusion: On the basis the literature and our own results we recommend that patients with kidney tumour and tumour thrombus in the inferior vena cava are evaluated with a view to operation.

The prognostic significance of DNA index (DI), S-phase fraction, and heterogeneity determined by flow cytometric DNA analysis was assessed in a prospective study of 249 newly diagnosed transitional cell carcinomas of the bladder. The median observation time was 4.8 years. A total of 456 subpopulations were detected. The S-phases could be estimated in 299 subpopulations. A DI > 1.25 or an S-phase above 9.7% were strongly correlated to invasiveness. One hundred and ten patients were treated with transurethral resection (TUR). Relapse-free survival could not be predicted by the DNA-derived parameters. Univariate analysis of survival showed prognostic significance of diploidy (0.98 < DI < or = 1.02, P = 0.02), hypotetraploidy (1.50 < DI < or = 1.96, P = 0.002), and S-phase size (P = 0.008). Multivariate analysis pointed to the T-classification (RR = 1.64) and hypotetraploidy (RR = 1.57) as prognostic parameters for survival of TUR-treated patients. One hundred and thirty-nine patients received radiotherapy (RT). A significantly better response was found for tumors with a subpopulation with a hypertetraploid DNA content (DI > 2.04, P = 0.05), and a significantly worse response for subpopulations with a maximum S-phase > 24.5% (P = 0.04). T-classification and histological grade had no predictive value. A logistic regression analysis indicated an estimated probability of response to RT of 77% for tumors with a DI > 2.04 and an S-phase < 24.5%, whereas tumors with a DI < 2.04 and an S-phase > 24.5% had only a 28% probability of response. The poor response to RT, predicted by an S-phase > 24.5%, translated into a poor survival, whereas the better treatment response found for patients with a DI > 2.04 did not result in a longer survival. Multivariate analysis pointed to S-phase (RR = 1.70), T-classification (RR = 1.60), and grade (RR = 0.65) as independent prognostic parameters for survival of RT-treated patients.

A total of 102 men treated for germ cell tumor with chemotherapy containing cisplatin was referred for a secondary operation with signs of tumor in the retroperitoneum or chest. Of the patients 85 underwent laparotomy, 14 underwent thoracotomy and 3 had both operations. Residual tumors were completely resected in 66 patients and incompletely resected in 30, while no tumor was found in 6. The resected specimen was malignant in 18 patients, of whom 11 had complete removal of all malignant tissue. All patients with malignancy in the resected specimen received further chemotherapy. Long-term disease-free status was obtained in 75% of those patients who had a complete resection, compared with 14% in the group with incomplete resection. There was no evidence of malignant disease at operation in 78 patients but 5 of them later died of the disease. Malignant tissue was present in the residual tumor in only 1 of 15 patients whose primary tumor was seminoma alone. Resection was attempted in 14 patients despite abnormal tumor markers preoperatively. Only 5 of these patients achieved a disease-free status and 2 of them died later of malignant disease. Over-all 79 of the 102 patients are without evidence of disease (medium postoperative observation 23 1/2 months). We conclude that a secondary operation constitutes an important part of the treatment of patients with germ cell cancer.

From 1983 to 1986 183 patients with transitiocellular carcinoma of the urinary bladder, category T2-T4a, entered a randomized study. The patients were allocated to receive either preoperative irradiation (40 Gy) followed by cystectomy or radical irradiation (60 Gy) followed by salvage cystectomy in cases of residual tumor. The two randomization groups were comparable in regard to sex, age, T-categories, tumor size, histological grade and concomitant dysplasia. The two randomization groups included 88 and 95 patients respectively. The treatment plan was followed by 66 patients (75%) in the planned cystectomy group and by 88 (92%) in the radical radiotherapy group of which 27 (28%) were treated with salvage cystectomy. The results showed a trend to a higher survival rate following the combined treatment with preoperative irradiation and cystectomy compared to radical irradiation followed by salvage cystectomy in case of residual tumor, but a statistical significant difference could not be demonstrated. The lack of difference also applied according to the actually given treatment. There was no difference in surgical complications between planned and salvage cystectomy and there were no postoperative deaths among the cystectomized patients. The type of late complications was different in the two treatment groups, but there were no major differences in the number of complications except for the fact that all male patients experienced erective impotence after cystectomy. The T-category, response to radiotherapy and frequency of lymph node metastases were found to be of prognostic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

The concept of using either alternating or sequential combination chemotherapy with non-cross-resistant combinations was tested in a randomized trial including 301 previously untreated patients with advanced epithelial ovarian carcinoma. The sequential schedule consisted of CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) followed by PH (cisplatin, hexamethylmelamine) in nonresponders, CAF- greater than PH (n = 157), and the alternating regimen consisted of CAF/PH (n = 144). With a median observation time of 54 months, no statistically significant differences were found between the pathologically complete response (PCR) rates of 17% and 16%, respectively, nor were there any statistical differences in median disease-free survival for PCR patients (CAF- greater than PH 34+ months and CAF/PH 26+ months), in overall survival (28 and 24 months, respectively), or in time to treatment failure (10 and 11 months). The overall estimated cure rate was 13%. An equal degree of myelosuppression was seen with the two regimens, whereas neuro- and nephrotoxicity were more pronounced when PH was given sequentially to CAF than with the alternating schedule. We conclude that the sequential and the alternated use of doxorubicin- and platinum-based regimens yield equivalent results and that other approaches should be investigated to improve treatment effects.

Occupational risk of bladder cancer (including papilloma) was investigated as part of a case-referent study in Copenhagen. Occupational histories were obtained on 389 cases and 790 referents drawn at random from the general population of the study area. When persons with missing information were excluded, a total of 371 cases (280 men, 91 women) and 771 referents (577 men, 194 women) were left for analysis. After adjustment for tobacco smoking, age, and sex, significantly increased relative risks were observed for occupation in land transport, in particular bus, taxi, or truck driving. A statistically significant trend was seen with duration of employment in these trades. Based on a logistic regression analysis, a relative risk (RR) of 1.3 was determined for 10 years of employment in the trade. An association was also found for employment in trades undertaking painting (RR = 1.4 for 10 years' employment), and a significant trend emerged for duration of employment. A positive association with employment in the textile and leather industry disappeared after adjustment for tobacco smoking, and no association with duration of employment emerged. No association was found with employment in the chemical, rubber, iron and metal industries or in health services.

The results of salvage cystectomy for persistent or recurrent tumour following definite radiotherapy in 47 patients are reviewed. The calculated five-year survival rate was 25% for all stages, with a significantly better survival for the low pathological stages. Operative mortality was 12.8%. It was concluded that salvage cystectomy is a suitable supplement in the treatment of bladder cancer in spite of the considerable operative mortality and complication rate.

During the years 1979 to 1981 a population-based case-control study of bladder cancer including papillomas was performed in Greater Copenhagen. After exclusions some 388 patients (290 males; 98 females) and an age- and sex-matched group of 787 controls (592 males; 195 females) remained for analysis. Controls were selected at random from the general population of the study area. All persons were interviewed concerning use of artificial sweeteners in addition to their exposure to a number of other known or suspected risk factors for bladder cancer. Fifty-five male bladder cancer patients (19.4%) and 150 controls (25.7%) had at some time used artificial sweeteners regularly. Among females 27.1% of cases and 25.9% of controls regularly used sweeteners. In neither sex was the relative risk significantly increased in users compared with non-users of artificial sweeteners. The relative risk of 0.78 in the two sexes combined was not significantly different from 1.0 (95% C.I.: 0.58-1.05). There was no indication of a regular increase in risk with increasing daily consumption of table-top sweeteners nor was there any indication of an increase in risk with a duration of regular use of artificial sweeteners. Taking into account a possible latency period between first regular use and bladder cancer development did not change the finding of an absence of association between use of artificial sweeteners and the risk of bladder cancer. Neither saccharine nor cyclamate users had an increased risk of bladder cancer. This population-based case-control investigation provides further evidence that it is highly unlikely that the consumption of artificial sweeteners has contributed to current bladder cancer rates in man.

A controlled study has been conducted to ascertain whether administration for 8 months of a vitamin A-acid analog, Tigason, could prevent recurrences of non-invasive bladder tumors. Eligible were 73 patients, 33 in the Tigason group, and 40 in the placebo group. The results indicate that Tigason, as used in this study, is ineffective as prophylaxis. Side effects to Tigason urged 17 patients to drop out from the study mostly due to symptoms from skin and mucous membranes. The discussion considers different reasons for the lack of effect and concludes that more tolerable vitamin A-acid analogs are needed if further studies of prevention of non-invasive bladder tumors are to be carried out.

During the years 1979-1981, a population-based study of 388 patients with bladder cancer, including papilloma, and of 790 controls was conducted in Greater Copenhagen. No pronounced difference between cases and controls of either sex was observed for bladder infection, kidney infection or bladder stones. Women with kidney stones had a significantly elevated relative bladder cancer risk (RR = 3.7; 95% CI = 1.2-12.1); the risk for bladder cancer was also increased (RR = 1.5), although not significantly so, in women who had ever had a 'kidney disease'. A review of the existing studies in humans and in animals of the association between bladder infection and cancer reveals a need for studies to determine whether urinary-tract infections increase either the true risk for bladder tumours or only complications of early bladder cancer before a clinical diagnosis has been made.

A 71-year-old man developed severe hemorrhagic proctitis 1 year after pelvic irradiation for carcinoma of the urinary bladder. Conservative treatment as well as performance of a colostomy failed to control the rectal bleeding. After irrigation of the rectum with a formalin solution the bleeding stopped, and no recurrence has been observed for the next 14 months.

Fifteen patients with incurable gynecological cancers, all primary radiation treated and all having severe urinary discomfort due to urinary tract injuries were retrospectively examined after urinary conduit diversion. All have been followed-up until termination or until all survivors had lived for 6 months after the operation. Twelve of the 15 were discharged from the hospital, 10 of whom survived the first 6 months. Of those discharged 82% of the cumulated sum of postoperative observations days was spent out of the hospital. At the end of the observation period nine patients had been supplied with a colostomy as well, thus having double stomas. All six patients still alive declared in retrospect that given the choice again, they would still be willing to undergo the operation.

During the period 1976-83, 47 women were operated on for recurrent or persistent cancer of the uterine cervix following initial radiation therapy. The operations performed were Wertheim's operation combined with dissection of the pelvic nodes, or some type of pelvic exenteration. With a 5-year survival of 31% in our material, surgical treatment of centrally located recurrences is a realistic possibility. We recommend an exenterative procedure as the operation is technically easier and the complications require less radical surgical treatment. The operation should only be done on narrow indications in the hope of achieving a cure, and the selection of patients must thus be stringent.

Two hundred and fifty biopsy specimens from the contralateral testis in patients with unilateral germinal testicular cancer were analysed by light microscopy for carcinoma-in-situ changes. Changes were found in 13 (5.2%) patients. One-third of patients with an atrophic contralateral testis (volume less than or equal to 12 ml) and one-fifth of patients with a history of cryptorchidism had changes in the remaining testis. In the present series 85% of cases with carcinoma-in-situ changes would have been diagnosed if the one-fifth of the patients having an atrophic testis or a history of cryptorchidism or both had been screened. Since the natural course of carcinoma in situ in the contralateral testis of patients with germinal testicular cancer has not been established, the patients are being re-evaluated frequently. To date two patients with carcinoma in situ have developed a second cancer.

The risk of second primary cancer was evaluated in 29,128 patients who developed tumors of the urinary tract, including benign and malignant tumors of the renal pelvis and ureter and bladder papillomas in Denmark between 1943 and 1980. Among 9,162 persons with kidney cancer, 416 developed a second primary tumor [relative risk (RR) = 1.4]. Among 19,966 persons with bladder cancer, 1,423 developed a second primary tumor against 1,239 expected (RR = 1.1). The risk of bladder cancer was increased following kidney cancer in both men (RR = 6.3) and women (RR = 10.1), and kidney cancer was increased in both men (RR = 2.9) and women (RR = 4.5) following bladder cancer. These risks were particularly pronounced for cancers occurring in the ureter and renal pelvis. Etiologic similarities are likely explanations for these observations, which also emphasize the role of host factors and the multifocal nature of urothelial tumors. A decrease in relative risks since diagnosis of the first primary cancer was seen that may partly be attributed to a lessening of the intensity of medical surveillance with time. Among long-term survivors with kidney cancer, increased risks were observed for colon and pancreatic cancers, which may be related to treatment; approximately 25% received radiotherapy. Among bladder cancer patients, increased risks of cancers of the lung and larynx occurred, probably due to tobacco smoking. A slight elevation of prostate cancer (RR = 1.3) may be attributable to medical surveillance. Unexpected findings were the significant deficits of cancers of the stomach and rectum among patients with bladder cancer and stomach cancer among those with kidney cancer.

Smoking habits and occupational exposures were investigated for 96 patients with cancer of the renal pelvis and ureter (including papilloma) and 294 hospital controls. In comparison with persons who never smoked, significantly increased relative risks were seen for smokers of cigarettes alone (RR = 2.6; 95% CI: 1.0-6.7) and in combination with other types of tobacco (RR = 3.8; 95% CI: 1.3-11.5). Non-significantly increased relative risks were observed for pipe smokers (RR = 2.2; 95% CI: 0.1-97) and for mixed pipe, cigar, and cigarillo smokers (RR = 6.5; 95% CI: 0.4-21.2). A strong dose-effect (p less than 0.001) relationship was seen between the lifetime total amount of tobacco smoked and the risk of pelvis-ureter tumors, with the heaviest smokers having an 8-fold risk. Comparison with the dose-effect relationship for a parallel study of bladder cancer indicated that the relationship with tobacco was stronger for pelvis-ureter tumors. Deep inhalation of cigarette smoke increased the risk (RR = 3.4; 95% CI: 1.9-6.1), while stopping smoking (RR = 0.6; 95% CI: 0.3-1.1) and use of filter cigarettes (RR = 0.5; 95% CI: 0.3-0.9) decreased the risk. Significantly increased risks emerged for employment in the chemical, petrochemical and plastics industries (RR = 4.0; 95% CI: 1.6-9.8), and for exposure to coal and coke (RR = 4.0; 95% CI: 1.2-13.6), asphalt and tar (RR = 5.5; 95% CI: 1.6-19.6). Cigarette smoking accounted for 56% of male and 40% of female pelvis and ureter tumors in eastern Denmark.

A population based study of 388 cases of bladder cancer including papillomas and 787 controls in Greater Copenhagen confirmed the role of smoking in the aetiology of bladder cancer. Significantly increased relative risks were found for persons who had smoked only cigarettes (RR = 2.9; both sexes combined) and for mixed smokers including cigarettes (RR = 3.6; both sexes combined). Multiple logistic regression analysis showed significant influences of the amount (pack years) of cigarettes smoked and a reduced risk among persons who had stopped smoking. No significant effects of smoking pipe or cigars/cigarillos were apparent, and the present study does not confirm previous suggestions of associations between the smoking of cigars/cigarillos and bladder cancer in Denmark. Only a slight increase in relative risk with the amount smoked was found. The influence of smoking on bladder cancer risk was similar for tumours in stages T1 and T2-4 at diagnosis and also for tumours of grades 1-2 and grades 3-4 at diagnosis.

We observed nine cases of transitional-cell carcinoma of the urinary bladder among patients who had had long-term treatment of other cancers with cyclophosphamide. Seven of the bladder carcinomas occurred within a cohort of 471 patients treated for non-Hodgkin's lymphomas. In this cohort the relative risk of bladder cancer was 6.8 (95 percent confidence interval, 3.2 to 14.2). The cumulative risk (mean +/- SE) was 3.5 +/- 1.8 percent 8 years after the start of treatment with cyclophosphamide and 10.7 +/- 4.9 percent after 12 years. Three of the nine patients were 50 years of age or younger; seven died with progressive bladder cancer. Subsequently, an additional patient had acute nonlymphocytic leukemia. Hemorrhagic cystitis was observed in 33 patients (cumulative risk, 11.8 +/- 2.1 percent after five years). Development of carcinoma of the urinary bladder was not related to previous hemorrhagic cystitis. The results caution against long-term treatment with cyclophosphamide for diseases with a favorable prognosis.

An analysis of incidence, risk factors and treatment results of intestinal obstruction caused by carcinoma of the ovaries was performed in 310 consecutive patients with carcinoma of the ovaries, The International Federation of Gynecology and Obstetrics stage IIB to IV, treated with combination chemotherapy. With a median observation time of 46 months, the incidence was 14 per cent and the cumulated risk was estimated to be 26 per cent at five years after treatment was begun. Risk factors were stages IIIB and IV, residual primary tumor size greater than 2 centimeters and presence of intestinal carcinomatosis at primary laparotomy. There was no difference in the survival time between 16 conservatively treated patients and 25 surgically treated patients (a median of 30 and 68 days, respectively, p greater than 0.30). The complication risk of surgical treatment was high (64 per cent), and surgical benefit--defined as survival greater than 60 days with total palliation of intestinal symptoms--was achieved in only 32 per cent.

Biopsy specimens from the contralateral testicle in 50 consecutive patients with germinal testicular cancer were examined for carcinoma in situ. Three out of 21 men with seminomas and one out of 29 with other types of germinal cancer (8%) had carcinoma in situ in the contralateral testicle without any clinical signs. One of these men developed early invasive germ-cell cancer 46 months after carcinoma in situ was first diagnosed. The others have been followed up for less than a year without signs of tumour growth. If these results are confirmed routine biopsy of the contralateral testicle in patients with germinal cancer may be indicated.

Analgesic intake was investigated for 96 patients with cancer of the renal pelvis and ureter (including papillomas) and 294 hospital controls. In comparison with persons who never used analgesics, increased relative risks (RR) were seen for users of phenacetin-containing drugs after adjustment for smoking and high-risk occupational exposure (men: RR = 2.4; women: RR = 4.2). A significant relative risk for aspirin use among women was also observed. There was an indication of a dose-effect relationship for both types of analgesics. The influence of phenacetin and aspirin on the development of renal pelvis and ureter tumours could not be separated since in this study the two compounds occurred so frequently in the same formulation. Experimental studies and phenacetin metabolism makes it biologically most relevant to attribute the observed association in the present study to the phenacetin component of the drugs.

A material of 746 consecutive patients with tumours of the bladder from three hospitals in Greater Copenhagen for the period 1968-1974 is presented. This is the result of The Copenhagen Bladder Cancer Project. Some of the aims of the project were to describe the manifestations of bladder cancer by means of a number of examination parameters. The material may be regarded as representative for the region. About 80 percent of the patients are men, and the mean age is 66 years, but higher for patients with deeply invasive tumours and tumours of low degree of differentiation. Haematuria was the presenting symptom in 84 percent of the patients, and only 3.4 percent had urinary tract infection as sole first symptom. The interval from first symptom to hospitalisation was an average of 7.6 months, but less for cases of deeply invasive tumours and tumours of low degree of differentiation. About 60 percent of all bladder tumours are evaluated as being without invasion of the bladder nusculature, and 59 percent of the tumours are of a high degree of differentiation (Grade 0+I+II). Squamous cell carcinomas are found in about three percent and adenocarcinomas in about one percent of the cases. Benign papillomas, corresponding to Grade 0 tumours, are found in only one percent of the cases. About 50 percent of all transitional cell tumours are both superficial and show a high degree of differentiation. Grade II tumours show invasive growth in at least 25 percent of the cases and Grade III tumours in at least 77 percent. The bladder tumours are papillomatous in 66 percent of the cases, and 24 percent of the patients have more than one tumour in the bladder. Intravenous urography showed a pathological condition in 70 percent of the patients.

From 1977 until 1980, 179 patients with newly diagnosed FIGO stages IIB, III or IV ovarian adenocarcinoma were randomized in a two-armed clinical trial: dihydroxybusulfan (B) 600 mg/m2 p.o. for 4-6 weeks q 12 weeks or cyclophosphamide (C) 150 mg/m2 p.o. for 7 days q 4 weeks vs a combination of cyclophosphamide 400 mg/m2 i.v., doxorubicin 30 mg/m2 and 5-fluorouracil 400 mg/m2 i.v., days 1 and 8 q 4 weeks (CAF). In addition, stage IIB patients were randomised to +/- pelvic irradiation. The patients were stratified according to anatomic stage. The treatment groups were comparable with respect to performance status, age and histology. Twenty-three patients were excluded because of protocol violation, leaving 156 patients evaluable for survival with an observation period of 3-6 yr. Twenty patients were in stage IIB, while the remaining 136 patients were classified as stages III and IV. No statistically significant difference was found in survival or response between the two single agents. The overall median response rate (single drug: 27%; CAF: 47%) and the median response duration (single drug: 5 months; CAF: 10 months) were significantly superior for the CAF group compared to the single agent group. No statistical difference in median survival was observed between single-drug treatment (12 months) and CAF (14 months), despite the fact that responders lived significantly longer than nonresponders (17 vs 10 months). In stage IIB patients receiving chemotherapy no benefit of pelvic irradiation was found. Thirty patients (19%) underwent second-look laparotomy, with 15 (50%) being completely free of disease. So far only one patient (7%) has relapsed. Two additional patients, who had microscopic disease removed at second-look laparotomy, seem to have been rescued by this procedure.

During the years 1979-1981 a population-based case-control study of bladder cancer including papilloma was performed in greater Copenhagen. A total of 371 patients (280 males; 91 females), and a comparable age- and sex-stratified group of 771 controls (577 males; 194 females) remained for logistic regression analysis. Controls were selected at random from the general population of the study area. All persons were questioned about their drinking habits with respect to coffee, tea and other beverages, as well as their exposure to a number of known or suspected risk factors for bladder cancer. After adjustment for tobacco smoking, the relative risk of bladder cancer in relation to coffee drinking was not statistically significant among either men or women. A significant association was found between bladder cancer and tea drinking among men, but with no regular trend for increasing consumption. An association was found between risk of bladder cancer and both total daily liquid intake and non-cola soft drinks. This population-based case-control study provides no evidence of an isolated influence of coffee drinking or caffeine intake on bladder cancer risk.

Carcinoma in situ in the contralateral testis was diagnosed in 27 of 500 patients (5.4%) with unilateral testicular germ cell cancer. Eight of the 27 patients received intensive chemotherapy for spread of their initial testicular cancer. Follow up biopsy studies did not detect changes of carcinoma in situ in any of these patients, and none developed a contralateral testicular tumour (observation time 12-88 months). Of the remaining 19 patients with carcinoma in situ, seven developed contralateral testicular cancer. The estimated risk of developing invasive growth was 40% within three years and 50% within five years. None of the 473 patients without carcinoma in situ detected by screening biopsy developed contralateral testicular cancer (observation time 12-96 months). No serious complications arose from the biopsy procedures. All patients with unilateral testicular germ cell cancer should be offered biopsy of the contralateral testis.

Twenty-four patients with residual tumor after intensive chemotherapy for advanced testicular germ-cell tumors were subjected to secondary surgery. Twenty patients had complete resection with the following distribution of histological types: 4 embryonal carcinoma, 9 mature teratoma and 7 fibrous tissue. Eighteen of these patients remain free of disease. Four patients had incomplete resection. Two of these patients with embryonal carcinoma died later despite further treatment; 2 patients with teratoma remain free of disease. Secondary surgery is recommended in cases where residual tumor is found after intensive chemotherapy and where tumor markers are not elevated.

The aim of this study has been, on the basis of 746 cases of cancer of the bladder from The Copenhagen Bladder Cancer Project, to assess the prognosis in relation to the tumour classification employed. The following five-year survival rates were found: T1, 59.8 percent, T2, 39.0 percent, T3, 19.7 percent, T4, 5.7 percent. There are significant differences in survival between the different T categories. The survival rates were also calculated for the different histological grades, and significant differences were also found here. Both the T classification and the histological grading are, therefore, relevant prognostic criteria. Papillomatous tumours have the same survival, whether solitary or multiple, but solid tumours have a poorer prognosis than papillomatous tumours. Tumour size is likewise a significant prognostic criterion. Of special interest has been the results of radiotherapy related to the same parameters. Neither the T classification nor the histological grading can be used as prognostic criteria for patients in the present material who were treated by radiotherapy. The overall five-year survival for patients treated by radiotherapy was 22 percent. With the investigative parameters employed, it is not possible in advance to select the group of patients with radiosensitive tumours.