Abstract: Abstract
OBJECTIVE:
Non-neuronal acetylcholine (ACh) has been suggested to be a mediator for the development of various types of cancer. We analyzed a possible role for this molecule in carcinogenesis and/or progression of human colon cancer, in patient biopsies harvested from the colon during surgery. We addressed whether ACh synthesis (by choline acetyltransferase) and/or degradation (by ACh esterase), as well as the expression of the α7-subtype of the nicotinic ACh receptors, and the peptide ligand at the α7 receptors, secreted mammalian Ly6/urokinase-type plasminogen activator receptor-related protein-1, respectively, are deranged in tumor tissue as compared with macroscopically tumor-free colon tissue.
METHODS:
A total of 38 patients were grouped for analysis based on their respective Dukes stage (either Dukes A + B or C + D). A mucosal tissue sample was harvested from macroscopically tumor-free colon tissue (i.e. control tissue), as well as from the tumor, and protein lysates were prepared for quantitative Western blotting. Full-thickness specimens were taken for immunohistochemistry.
RESULTS:
For all the above named markers, there was a significant difference between control and tumor tissue with regard to protein levels, and there was, in addition, a significant difference in protein levels between the Dukes A + B and C + D groups.
CONCLUSION:
The current findings may suggest a role for ACh in colon carcinogenesis/cancer progression; the data obtained could have prognostic and/or therapeutic significance for this disease.
Abstract: Abstract
OBJECTIVES:
To develop and evaluate a simulation model making it possible to evaluate the accuracy and efficiency of different triage methods; to compare the results of physiological and anatomical triage performed by medical staff with different levels of skills with the use of this model.
DESIGN AND OUTCOME MEASURES:
A simulation model was created based on patient cards giving sufficient physiological data as a base for physiological triage and anatomical data as description of findings at exposure, providing a base for anatomical triage. Three groups with different skills in disaster medicine, nurse students (n = 23), ambulance nurses (n = 20), and surgeons (n = 30), performed triage based on the patient cards. The outcome was given as potential avoidable mortality. The results of the triage for the two methods were compared to the result of the same triage performed by an expert group.
RESULTS:
Differences in triage: Within the groups, the difference between the two triage methods was only significant for the surgeons (p < 0.001), who had a better result using the anatomical triage. For the "physiological triage," there were no significant differences between the three groups. Regarding the results for the "anatomical triage," there were significant differences between both the nurse students and the surgeons (p < 0.001) and the ambulance nurses and the surgeons (p < 0.05). Results in distribution of patients and potential avoidable mortality: Within the groups, the difference between the two methods was significant for all the groups (nurse students, p < 0.01; ambulance nurses, p < 0.01; and surgeons, p < 0.001). They all had a better outcome with anatomical triage (nurse students, 6.1 percent; ambulance nurses, 6.1 percent; and surgeons 19.5 percent less mortality than physiological triage). The group that made the best outcome from physiological triage was the ambulance nurses who had a significantly better result than both nurse students (p < 0.01) and surgeons (p < 0.001). The mean mortality rate for ambulance nurses was 31.1 percent, nurse students, 37 percent, and surgeons was 38.1 percent. Regarding the anatomical triage, there was a significant difference (p < 0.001) between the groups of nurse students (30.9 percent mortality) and surgeons (18.9 percent mortality). The differences between the rest of the groups were also significant (p < 0.05).
CONCLUSIONS:
The model developed for this study made it possible to compare different methods of triage and also triage performed by staff of different levels of training and experience. Anatomical triage for all test groups in this study gave significantly better results than physiological triage regarding calculated outcome and this difference increased with increasing experience.
Abstract: Adrenocortical carcinoma (ACC) is a rare tumour disease with sinister prognosis also after attempts to radical surgery; better prognosis is seen for low-stage tumours. Adjuvant treatment with the adrenolytic drug mitotane has been attempted, but not proven to prevent from recurrence. The drug may offer survival advantage in case of recurrence. The aim of this single-centre study (1979-2007) of 43 consecutive patients was to evaluate the long-term survival after active surgical treatment combined with monitored mitotane (to reduce side effects of the drug). The series is unique, since all patients were offered a period of mitotane as adjuvant or palliative treatment; six patients refused mitotane. Despite a high proportion of high-stage tumours (67%), the complete resection rate was high (77%). The disease-specific 5-year survival was high (64.1%); very high for patients with low-stage tumours without evident relation to mitotane levels. Patients with high-stage tumours had a clear survival advantage with mitotane levels above a threshold of 14 mg/l in serum. The hazard ratio for patients with high mitotane levels versus all patients indicates a significant effect of the drug. The results indicate that adjuvant mitotane may be the standard of care for patients with high-stage ACC after complete resection.
Abstract: Urokinase-type plasminogen activator (uPA) is an important factor for tumour cell invasion and metastasis. We recently showed that acetylcholine is an autocrine/paracrine growth factor for the human colon cancer cell line, HT-29, in part via the α7 subtype of the nicotinic acetylcholine receptors. In the current study, we investigated whether acetylcholine participates in the regulation of the protein expressions of also uPA and its receptor (uPAR) in the HT-29 cell line. Such were investigated by immunocytochemistry and Western blotting, and quantitation of uPA secretion was undertaken by ELISA. Stimulation of the cells for 24h with nicotine caused increased uPA secretion with peak effect (78% above the control) occurring at a nicotine concentration of 10nM. This effect was markedly inhibited by α-Bungarotoxin, thus showing the involvement of α7 nicotinic acetylcholine receptors. Basal uPA secretion was found to be partly dependent on ongoing activation of nicotinic receptors, suggesting tonic production of acetylcholine. Conversely, there was no cholinergic influence on the expression of uPAR. The current findings demonstrate novel aspects of receptor-mediated regulation of tumour metastatic potential via uPA secretion. This may suggest future pharmaceutical strategies in treatment of colorectal cancer.
Abstract: Background: The consequences of a major incident at a sporting event could be catastrophic. Therefore, there should be an estimation of the healthcare resources at such events as part of the planning. Although there are National guidelines (e.g., Planning Safe Public Events: Practical Guidelines in Australia) defining the role of the healthcare system at sporting events, these guidelines either lack a simple calculating method to estimate the need for healthcare resources or the methods are complex and impractical to use. The objective of this study was to find a safe and easy method for the estimation of healthcare resources at sporting events. Methods: A model for the estimation of healthcare resources at music events recently has been approved in Sweden. After minor adjustments, this model was used at sport events by a number of planning officers. The models' accuracy and usability was evaluated by analyzing its outcome in a pilot and a controlled study using different sporting and non-sporting scenarios. Results: The pilot study showed that the model was valid and easily could be used for various sporting events. The obtained estimations were consistent with the methods used by experienced planning officers in 97% of cases. The results of the controlled study showed that by using this model, the minimum amount of resources required easily could be calculated at sporting events and by people with different backgrounds. Conclusions: This model safely can be used at sporting events.
Abstract: The timely provision of emergency medical services might be influenced by discrepancies in triage-setting between emergency medical dispatch centre and ambulance crews (ACR) on the scene resulting in overloaded emergency departments (ED) and ambulance activities. The aim of this study was to identify such discrepancies by reviewing ambulance transports within a metropolitan city in the western region of Sweden.
Methods
All data regarding ambulance transports in Gothenburg, Sweden, during a 6-month period were obtained and analyzed by reviewing the available registry.
Results
There was a discrepancy between emergency medical dispatch centre and ACR in priority setting, which may result in a number of unnecessary transports to the hospital with consequent overloading of ED and a negative impact on ambulance availability.
Conclusion
Appropriate ambulance use is one important part of emergency preparedness. Overuse results in decreased emergency medical services (EMS) availability and ED-overcrowding. Several factors, such as an imprecise triage system and increased public demands, may influence such overutilization. Improving the triage system and comprehensive public education on appropriate use of ambulances are two important steps toward a better use of national EMS resources.
Keywords Ambulances - Emergency Medical Services - Triage
Abstract: Introduction: Despite a global increase in conservative treatment of blunt
liver injuries, the number of surgically treated traumas in one major trauma
center in Iran has increased. The aim of this study was to unveil the reasons
behind this increase in operative management by studying 228 consecutive
patients at this regional center.
Hypothesis: The increased number of liver injuries operated upon is due to
the lack of a solid, well-defined trauma system.
Methods: A retrospective review of all patients admitted for liver trauma at
Bahonar Hospital, Kerman, Iran, from March 2001 until March 2006 was
conducted. Patient data were collected, studied and statistically processed with
regard to demographics, clinical and laboratory findings, surgical procedures,
complications, and mortality.
Results: All patients who were admitted between 30â360 minutes after injury
were included.Twelve hemodynamically stable patients were treated conservatively
in an ordinary surgical ward.The remaining 216 patients, 153 of whom
had blunt injuries, were hemodynamically unstable. A total of 70 patients
were in hemorrhagic shock at the time of arrival. Hemodynamically unstable
patients with either the suspicion of associated injuries and/or who displayed
clinical deterioration and could not be observed in an ordinary surgical ward
were treated surgically. The majority of patients who were operated upon in
this series had a grade-II liver injury. The total mortality rate in surgically
treated patients was 18.1%. None of the patients treated conservatively died.
Conclusions: Despite the low grade of their liver injuries, the high number of
surgically treated patients in this series was due to the absence of a valid trauma
system. This result should encourage the authorities to review current
trauma systems and trauma surgical guidelines.
Abstract: 1 Possibly acting via l-opioid receptors (MORs), morphine inhibits the formation of
experimentally induced postoperative abdominal adhesions in rats. Mesothelial cells may
participate in adhesion formation by secreting mediators that interfere negatively with
fibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesion
mediators from mesothelial cells. This study aimed to investigate whether human mesothelial
cells express MOR-1; if so, such could constitute a site of action for morphine in adhesion
prevention.
2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared for
immunocytochemistry and Western blotting.
3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in the
nuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to those
obtained with a control lysate from cells known to express MORs. In addition, we found
MOR-1 expression with nuclear and cytoplasmatic localization in biopsies from human
abdominal adhesions.
4 The current findings may suggest that morphine could interact directly with mesothelial cells
via MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering with
the release of pro-adhesion factors from these cells.
Abstract: ABSTRACT: BACKGROUND: Although disasters and major incidents are difficult to predict, the results can be mitigated through planning, training and coordinated management of available resources. Following a fire in a disco in Gothenburg, causing 63 deaths and over 200 casualties, a medical disaster response centre was created. The center was given the task to coordinate risk assessments, disaster planning and training of staff within the region and on an executive level, to be the point of contact (POC) with authority to act as "gold control," i.e. to take immediate strategic command over all medical resources within the region if needed. The aim of this study was to find out if the centre had achieved its tasks by analyzing its activities. METHOD: All details concerning alerts of the regional POC was entered a web-based log by the duty officer. The data registered in this database was analyzed during a 3-year period. RESULTS: There was an increase in number of alerts between 2006 and 2008, which resulted in 6293 activities including risk assessments and 4473 contacts with major institutions or key persons to coordinate or initiate actions. Eighty five percent of the missions were completed within 24 h. Twenty eight exercises were performed of which 4 lasted more than 24 h. The centre also offered 145 courses in disaster and emergency medicine and crisis communication. CONCLUSION: The data presented in this study indicates that the center had achieved its primary tasks. Such regional organization with executive, planning, teaching and training responsibilities offers possibilities for planning, teaching and training disaster medicine by giving immediate feed-back based on real incidents.
Abstract: In response to the current economic constrains within the healthcare systems, different action plans and reforms, including tax increases, have been deployed to decrease the costs and to increase healthcareâs effectiveness. It is, however, the time to realise that these measures are not enough and prioritisation might be the only way to cure this chronic condition.
Abstract: Increasing cost within the healthcare systems has enforced dramatic changes to prevent a disastrous outcome and to make it more efficient. Financial constraints are obvious in the generic planning phase for a real disaster. Economical restrictions have a huge impact on disaster planning. It is now the time to decide which disasters we will see in the future.
Abstract: ABSTRACT: BACKGROUND: Hospital's capacity and preparedness is one of the important parts of disaster planning. Hospital-related incidents, a new phenomenon in Swedish healthcare, may lead to ambulance diversions, increased waiting time at emergency departments and treatment delay along with deterioration of disaster management and surge capacity. We aimed to identify the causes and impacts of hospital-related incidents in Region Vastra Gotaland (western region of Sweden). METHODS: The regional registry at the Prehospital and Disaster Medicine Center was reviewed (2006-2008). The number of hospital-related incidents and its causes were analyzed. RESULTS: There were an increasing number of hospital-related incidents mainly caused by emergency department's overcrowdings, the lack of beds at ordinary wards and/or intensive care units and technical problems at the radiology departments. These incidents resulted in ambulance diversions and reduced the prehospital capacity as well as endangering the patient safety. CONCLUSION: Besides emergency department overcrowdings, ambulance diversions, endangering patient's safety and increasing risk for in-hospital mortality, hospital-related incidents reduces and limits the regional preparedness by minimizing the surge capacity. In order to prevent a future irreversible disaster, this problem should be avoided and addressed properly by further regional studies.
Abstract: The new world, new technology and new means of transport not only make global cooperation easier, but also the distribution of new diseases. The new influenza A virus variant (H1N1)v, which has rapidly spread worldwide, offers new possibilities for cooperation and an unique opportunity to plan a mutual tactic against the pandemic.
Abstract: BACKGROUND: A trial in selected men suggested that antibiotic therapy could be an alternative to appendicectomy in appendicitis. This study aimed to evaluate antibiotic therapy in unselected men and women with acute appendicitis. METHODS: Consecutive patients were allocated to study (antibiotics) or control (surgery) groups according to date of birth. Study patients received intravenous antibiotics for 24 h and continued at home with oral antibiotics for 10 days. Control patients had a standard appendicectomy. Follow-up at 1 and 12 months was carried out according to intention and per protocol. RESULTS: Study and control patients were comparable at inclusion; 106 (52.5 per cent) of 202 patients allocated to antibiotics completed the treatment and 154 (92.2 per cent) of 167 patients allocated to appendicectomy had surgery. Treatment efficacy was 90.8 per cent for antibiotic therapy and 89.2 per cent for surgery. Recurrent appendicitis occurred in 15 patients (13.9 per cent) after a median of 1 year. A third of recurrences appeared within 10 days and two-thirds between 3 and 16 months after hospital discharge. Minor complications were similar between the groups. Major complications were threefold higher in patients who had an appendicectomy (P < 0.050). CONCLUSION: Antibiotic treatment appears to be a safe first-line therapy in unselected patients with acute appendicitis.
Abstract: 1. Secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is a recently discovered endogenous ligand at the alpha7 subunit of the nicotinic acetylcholine receptors. Previous reports have shown that SLURP-1 is expressed in normal human keratinocytes seemingly with a pro-apoptotic function. Conversely, such expression was markedly attenuated in transformed cells and it was suggested that the molecule could convey protection against malignant transformation. 2. In this study, we demonstrated the mRNA expression (by RT-PCR) and protein expression (by Western blotting and immunocytochemistry) of SLURP-1 in the human colon cancer cell line, HT-29. 3. Furthermore, we demonstrated the expression of SLURP-1 (by immunohistochemistry) in tumour cells of human colon cancer tissue, and, to a greater extent, in immune and smooth muscle cells of adjacent, macroscopically tumour-free colon tissue. 4. The current findings suggest that SLURP-1 participates in the regulation of gut immune functions and motility, as well as possibly playing a role in colon carcinogenesis/cancer progression.
Abstract: Objective: To study some of the aspects of communication between the Non-Swedish physicians and Swedish patients in Sweden.
Methods: Different aspects of communication between 84 Swedish patients and 85 non-Swedish physicians were studied by using questionnaire. We also followed a group of Non-Swedish physicians (n = 38) who received a supportive medical course before they applied for different positions and compared their chances of getting into the working market with previous groups without any educational support.
Results: Both linguistic and cultural factors showed to have a huge impact on the successful integration of Non-Swedish physicians into the Swedish healthcare system.
Conclusion: A successful integration in the Swedish health care sector depends on both linguistic and cultural competence. In order to integrate new personnel in Swedish healthcare sector, language courses should be accompanied by appropriate cultural education and training.
Practice implication: Our findings may be implemented as a new teaching model for a successful communication and integration of Non-Swedish healthcare personnel in the Swedish healthcare system.
Abstract: We have investigated the functional expression of mu-opioid receptors (MORs) in the human colon cancer cell line, HT-29. As revealed by immunocytochemistry, immunoreactivity was present in both the cytoplasm and nuclei of the cells. Challenge with morphine for 24 h (1 nM to 1 microM) barely affected cell proliferation, while the secretion of urokinase type plasminogen activator (a protease involved in invasion/metastasis) was markedly augmented by a concentration of 0.1 microM. Human colon cancer tissue from 14 consecutively operated patients was investigated by immunohistochemistry. MORs were found in the nuclei of colonocytes and immune cells of the lamina propria in tumor-free tissue. In tumor tissue, immunoreactivity was found in the membrane and often in the nuclei of tumor cells. The current findings suggest that morphine administration could affect tumor progression by interfering with, for example, invasive properties. Our demonstration of a nuclear expression of the MORs appears to be a novel finding.
Abstract: AIM: To evaluate the impact of a preoperative "triple non-invasive diagnostic test" for diagnosis and/or exclusion of common bile duct stones. METHODS: All patients with symptomatic gallstone disease, operated on by laparoscopic cholecystectomy from March 2004 to March 2006 were studied retrospectively. Two hundred patients were included and reviewed by using a triple diagnostic test including: patient's medical history, routine liver function tests and routine ultrasonography. All patients were followed up 2-24 mo after surgery to evaluate the impact of triple diagnostic test. RESULTS: Twenty-five patients were identified to have common bile duct stones. Lack of history of stones, negative laboratory tests and normal ultrasonography alone was proven to exclude common bile duct stones in some patients. However, a combination of these three components (triple diagnostic), was proven to be the most statistically significant test to exclude common bile duct stones in patients with gallstone disease. CONCLUSION: Using a combination of routinely used diagnostic components as triple diagnostic modality would increase the diagnostic accuracy of common bile duct stones preoperatively. This triple non-invasive test is recommended for excluding common bile duct stones and to identify patients in need for other investigations.
Abstract: BACKGROUND: Postoperative pain experienced by patients who undergo laparoscopic cholecystectomy may aggravate surgical complications, prevent early discharge, and cause readmission. This study aimed to evaluate the effectiveness of an intraoperative intercostals neural blockade for the control of postoperative pain after laparoscopic cholecystectomy. METHODS: In a prospective, double-blinded, clinical trial, 61 patients classified as American Society of Anesthesiology (ASA) 1 and 2 undergoing laparoscopic cholecystectomy were randomized to receive only general anesthesia (control group, n = 30) or general anesthesia plus intraoperative intercostals neural blockade using 0.5% bupivacaine-adrenaline at the right side (intercostals group, n = 31). Postoperative pain was assessed according to a pain severity score using a subjective analog visual scale (VAS) 6, 12, and 24 h after the surgery. Systemic narcotic injection was available to all surgically treated patients postoperatively according to their demand. The history, pain severity score, and all postoperative data were recorded for each patient. RESULTS: The pain severity score was significantly higher in control group than in the intercostals group (p < 0.001), suggesting that patients who received intercostals neural blockade had less pain postoperatively than the control group. CONCLUSION: Intercostals neural blockade may safely be used to reduce the postoperative pain after laparoscopic cholecystectomy.
Abstract: People addicted to opium rarely develop intra-abdominal adhesions after abdominal surgery. We aimed to evaluate the effect of opium or morphine on preventing postoperative adhesions in rats. Sixty-three rats were randomly divided into a control group, opium-addicted group, and morphine-addicted group in a double-blind study. Drug dependency was checked by using naloxone. Animals were then operated on and the cecum was abraded. At reoperation 3 weeks later the magnitude of adhesions was evaluated by a scoring system. There was a significant difference between the control, opium-addicted, and morphine-addicted groups with regard to the length (P < .001), thickness (P < .05), and severity of adhesions (P < .05). Opium or morphine reduces the severity of postoperative adhesions. Elucidation of the opioid receptor(s) involved in this process would enable the use of selective ligands and offer a pharmacologic strategy in preventing adhesion formation.
Abstract: A consecutive series of patients (68 females and 53 males) with pheochromocytoma (PC, n=110) or paraganglioma (PG, n=11) were treated at the Sahlgrenska University Hospital (1950-1997). During the observation period (15+/-6 years) 42 patients died versus 23.6 expected in the general population (P<0.001). There was no surgical mortality. Twenty patients died of cardiovascular disease, 11 of other tumors, and 7 of other diseases, but only 4 of PC/PG. The main causes of death in this regional series were cardiovascular diseases and tumor in a ratio of 1.3 versus 2.0 in the general Swedish population. Analysis of the mortality in all patients with clinically diagnosed PC (n=481, 259 women and 222 men) based on the National Cancer Registry (1957-1997) showed that the number of deaths in this cohort was 196 versus 153.4 expected (P<0.001). These patients had almost four times higher risk of dying of a tumor than did the general population (similar risk for females and males). There was no increased risk for cardiovascular death; in fact, the risk was lower than expected for men (22 vs. 38 expected). A second tumor diagnosed subsequent to PC occurred in 68 versus 31 expected. In men tumors of the liver and biliary tract and central nervous system and in women malignant melanoma and cervix carcinoma were most frequent. The results from the national series thus confirm an increased risk of a second tumor and increased tumor-related mortality in patients with PC.
Abstract: One hundred fifty-four consecutive patients with pheochromocytoma (PC, n=137) or paraganglioma (PG, n=17) were treated at our unit. Twenty patients had MEN 2, 15 VRD, and 1 VHL tumors. Twelve had malignant tumors and were classified according to mode of presentation: (1) Distant metastases (n=4); three underwent surgical debulking (with chemotherapy in one); and three had 131I-MIBG therapy. Within 4 years two patients died of tumor progression. (2) Locally advanced disease (n=4), all resected for cure. (3) Malignancy disclosed during follow-up after adrenalectomy with "benign" histopathology (n=4). All patients in groups 2 and 3 developed recurrence 9 (1-17) years after primary surgery; four underwent resection, one remains tumor-free. The others were treated chronically with phenoxybenzamine, combined with 131I-MIBG in one. These eight patients were observed 20 (5-35) years after primary surgery and 11 (1-19) years after recurrence. This series is population-based and may better reflect the natural history of malignant PC/PG than the series from national referral centers. Active surgical treatment and phenoxybenzamine resulted in low tumor-related mortality in groups 2 and 3; five patients died 8-30 years after diagnosis, four of PC/PG (three from group 2 and one from group 3) and one of other causes. We propose tumor uptake studies (MIBG- and octreotide scintigraphy) in patients with nonresectable metastases; to select individual radionuclide therapy data on the expression of CA-transporters/somatostatin receptors may be helpful. To diagnose PC/PG early, screening of adrenal incidentalomas has been suggested. In a regional population-based prospective study, 503 incidentalomas were reported during 18 months, but only one patient with PG was identified.
Abstract: The risk for bilateral tumors and long-term outcome after conservative cortical-sparing adrenal surgery was studied in a consecutive single-center series. One hundred fifty-four patients were operated on (1950-2004) for pheochromocytoma (PC=137), or abdominal paraganglioma (PG=17). Twenty had MEN 2 (16 MEN 2A; 4 MEN 2B), 15 von Recklinghausen's disease (VRD), and 1 von Hippel-Lindau (VHL) disease. Twelve patients had, or developed, bilateral adrenal medullary tumors; four with MEN 2A, four with MEN 2B, three with VRD, and one with probably hereditary PC associated with brain tumors/meningioma. Two patients with MEN 2B and one with MEN 2A with had bilateral adrenalectomy (adx). Three VRD patients, two MEN 2B and one MEN 2A patients had cortical-sparing surgery. Two patients were operated on unilaterally, but developed small contralateral tumors; one of these (MEN 2A) had a second asymptomatic PC diagnosed at an older age, so surgery was withheld; the other patient (hereditary PC syndrome) had a small contralateral PC diagnosed at autopsy 9 years later. Only three of nine patients with bilateral operations needed corticosteroid replacement after surgery. Four of six patients died of associated tumors (MTC and meningioma). The mean follow-up was 13 (1-25) years. Twelve MEN 2A patients with unilateral adx have been followed up for 20 (4-36) years without developing a second PC. Cortical-sparing adrenal surgery can safely be performed in the majority of patients with bilateral PC. On the basis of our long-term experience of MEN 2A we perform contralateral adrenal resection only if a second PC is confirmed. Five patients underwent adrenal exploration because of clinical and biochemical findings compatible with PC. Four had asymmetrical positive MIBG scans. They all underwent unilateral adx and diffuse medullary hyperplasia was confirmed (medullary weight estimated morphometrically to 1.0-3.4 g vs. normal weight 0.3-0.5 g in matched controls). These patients have been followed for 19 (5-27) years with normal clinical and biochemical findings. In this rare condition removal of the largest adrenal seems adequate.
Abstract: Det är knappt att de hörs, steg av fötter i vita fotriktiga inomhussandaler, mjuka och
tassande. Ljusa korridorer, väggar med scheman, plastblommor vid fönster och fina
neutrala âinstitutionsgardiner.â Dämpade röster, deltagande leenden, automatiska dörrar,
breda nog för en sjukhussäng. PÃ¥ akuten â en samling människor med väntande och
uppgivna ansiktsuttryck.
Nuläget: Långa väntetider, tajta och utmattande scheman för personalen med ett ökat antal
sjukskrivningar som följd. Ständiga påminnelser om anstående neddragningar och
sjukvårdens brister som förstasidesnyheter.
Ãnskas: Tid och pengar, arbetskraft som orkar, kan och vill, som ser möjligheterna och inte
problemen. Något som ökar vår återspegling av det nya mångkulturella samhället i vården
och som även passar in i våra personalvisioner och måldokument.
Abstract: OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997. PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment. SETTING: One referral centre for all patients from the western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra- or post-operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre- and post-operative hypertension did not influence the risk for death versus controls. CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.
Abstract: BACKGROUND: The aim of the present study was to report the risk of death in a national cohort of patients with aPC (adrenal PC) and their risk of developing a second tumour. METHODS: Using the National Cancer Registry, 481 patients (222 men and 259 women) with aPC in Sweden (1958-1997) were identified. Autopsy-based diagnoses were excluded. As control group the entire Swedish population was used and the risk of death in patients after diagnosis of aPC was compared with the normal risk taking age, sex and calendar year into account. The risk for a second tumour disease after diagnosis of aPC was also calculated. RESULTS: Patients with aPC had an increased tumour-related mortality after diagnosis of aPC. For both men and women this mortality was four times higher than for controls. Liver/biliary tract and CNS tumours in men; and malignant melanoma and uterine cervical cancer in women were significantly over-represented in the cohort of patients with aPC. CONCLUSION: Patients with aPC run an increased risk of developing additional cancers. Surveillance strategies may thus be necessary for these patients.
Abstract: Cell adhesion molecules (CAMs) are important regulators of tumor growth. The aim of the present study was to evaluate the expression pattern of CAMs in adrenal tumors regarding origin (cortex vs medulla) and biologic behavior (benign vs malignant). Eighty seven adrenal tumors were investigated by immunocytochemistry (ICC) using monoclonal antibodies against N-cadherin (NCAD), E-cadherin (ECAD), neural cell adhesion molecule (NCAM), and CD44. Western blotting was performed on 30 tumors using the same antibodies. Markers for proliferation (Ki-67) and catecholamine synthesis (tyrosine hydroxylase) were also analyzed in tumors by ICC. NCAD was expressed in 12/27 benign pheochromocytomas (BPCs) (12 familial cases), 8/8 malignant pheochromocytomas (MPCs), 28/30 adrenocortical adenomas, and 9/22 adrenocortical carcinomas. ECAD was expressed in 0/27 BPCs, 0/8 MPCs, 0/30 adrenocortical adenomas, and 2/22 adrenocortical carcinomas. NCAM was expressed in 26/27 BPCs, 7/8 MPCs, 21/30 adrenocortical adenomas, and 17/22 adrenocortical carcinomas. CD44 was expressed in 23/27 BPCs, 6/8 MPCs, 7/30 adrenocortical adenomas, and 4/22 adrenocortical carcinomas. Both cortical and medullary adrenal tumors expressed NCAD, NCAM, and CD44 but were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of tumors. NCAD was upregulated in MPCs, but downregulated in adrenocortical carcinoma. Thus, NCAD appears to be involved in the development of both cortical and medullary adrenal tumors.
Abstract: Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has been used for decades, but critical prospective trials on its role in residual disease or as an adjuvant agent after surgical resection are still lacking. The concept of a critical threshold plasma level of the drug must be confirmed in controlled studies. Because individual responsiveness cannot be predicted, the use mitotane is still advised for nonresectable disease. In case of cortisol or other steroid overproduction, several drugs (e.g., ketoconazole or aminoglutethimide) may be used. Chemotherapy with single agents (e.g., doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this refractoriness may be explained by the fact that ACC tumors express the multidrug-resistance gene MDR-1. Chemotherapy with multiple agents has been tested in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cisplatin associated with mitotane, achieving a response rate of 54%, including individual complete responses. To be able to make progress in treating advanced ACC disease, adjuvant multicenter trials must be encouraged. When mitotane-based therapies are used, monitored drug levels are mandatory.
Abstract: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. It has been difficult to establish a strict treatment program for ACC, and better treatment alternatives and diagnostic tools must be sought. Even though surgery is the treatment of choice, the role of surgery in advanced disease has been questioned. Eighteen consecutive patients were treated at our unit over a 22-year period (1975-1997). All patients underwent surgery and were followed by our protocol, which includes urinary steroid profiles, clinical examinations, analysis of steroid hormones, and radiologic investigations. Twelve patients received mitotane with drug concentration measurements to deliver an effective, nontoxic dose. The median duration of mitotane treatment was 12 months. Few side effects were observed. Four patients with low-stage tumors underwent second-look operations with no pathologic findings. Five patients were subjected to repeat operations, and the mean duration of the disease-free interval before repeat surgery for these patients was 59 months. There was a significant positive correlation between the disease-free interval and the observed survival after repeat surgery. Eleven patients with intentionally curative surgery had their urinary steroid profiles tested several times postoperatively. For five patients preoperative urine samples were also available. Steroid profiles indicated recurrent disease despite normal radiologic findings in two of these five patients. The follow-up ranged from 6 weeks to 24 years. The predicted 5-year survival was 58% according to the Kaplan-Meier method. We conclude that monitoring serum concentrations of mitotane makes long-term treatment possible with few side effects; steroid profile analysis can be used for early detection of tumor recurrence; and repeat surgery for recurrence is of value for patients with long disease-free intervals.
Abstract: Adrenocortical Carcinoma (ACC) is a rare malignant tumor with poor prognosis. Surgical removal is the only cure. Adjuvant use of mitotane, an adrenolytic drug with toxic effects, is controversial at best.
We evaluated our treatment program for patients with ACC including active surgery, adjuvant Mitotane treatment monitored by serum levels of the drug, and urinary steroid profiles in the follow-up to detect early recurrences.
Monitoring of serum levels of mitotane made long-term treatment possible in advanced disease with moderate side effects. Repeat surgery for recurrence was valuable in patients with long disease-free intervals, and urinary steroid profiles indicated early recurrence in individual patients. The 5-year survival of 30 consecutive patients with ACC (44% low Stage and 56% high Stage tumors) in our series was 64%. Patients with high Stage ACC (Stage III-IV), treated with mitotane after surgery, seemed to have better prognosis than expected. The results of cytotoxic treatment in advanced disease, using single or multiple cytotoxic agents, have so far been disappointing. Better results were obtained when mitotane was combined with the chemotherapy. Multicenter trials are needed in order to find the best combined medical therapy for these patients.
In order to find histopathological markers that can predict the prognosis in ACC and pheochromocytoma (PC), 87 adrenal tumors were analyzed for the expression of cell adhesions molecules by immunocytochemistry and Western blotting. Both cortical and medullary adrenal tumors expressed NCAD, NCAM and CD44, but all tumors were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of the tumors. During cell transformation and tumor progression NCAD expression seemed to be up-regulated in medullary tumors, but down-regulated in cortical tumors. Loss of NCAD may thus be involved in the development of malignant adrenocortical tumors. Thus, NCAD may function as tumor suppressor and lack of its expression may be of prognostic significance in adrenocortical tumors.
PC and paraganglioma (PG) rarely metastasize, but may still be life-threatening due to excessive secretion of catecholamine (CA). The cause of death in untreated PC/PG is hypertensive complications and in rare cases metastatic disease. The overall prognosis after surgical removal of PC has not been studied in detail. In the present study with long-term follow-up (1950-1997), 121 consecutive cases of surgically treated PC/PG were reviewed in order to evaluate outcome, cause of death and histopathological features.
There was no intra- or post-operative mortality. Eight patients proved to have malignant PC/PG during the period. The number of deaths in the series was higher than expected in the general population (p <0.001). The main causes of death were cardiovascular and other tumor diseases. High age at primary surgery and high urinary excretion of methoxy-CA were significant risk factors for death. For comparative reasons, all cases with adrenal PC, diagnosed in Sweden 1958-1997, were investigated. Patients in the national cohort had almost 4 times higher risk for death in tumor diseases than the general population, but no elevated death risk for cardiovascular diseases. Life-long follow-up of these patients is important not only to diagnose and treat cardiovascular diseases and recurrent PC at early Stage, but also to diagnose other tumor diseases.
