| 1. |
- Andersson, Yvette, 1972-
(författare)
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Sentinel Node in Clinical Practice : Implications for Breast Cancer Treatment and Prognosis
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The introduction of sentinel lymph node biopsy (SLNB) has conveyed several new issues, such as the risk of false negativity, long-term consequences, the prognostic significance of micrometastases and whether ALND can be omitted in sentinel lymph node- (SLN) positive patients.Archived SLN specimens from 50 false negative patients and 107 true negative controls were serially sectioned and stained with immunohistochemistry. The detection rate of previously unknown metastases did not differ between the false and the true negative patients. The risk of false negativity was higher in patients with multifocal or hormone receptor-negative tumours, or if only one SLN was found.In a Swedish multicentre cohort, 2216 SLN-negative patients in whom ALND was omitted were followed up for a median of 65 months. The isolated axillary recurrence rate was only 1.0%, and the overall survival was high (93%).The survival of 3369 breast cancer patients (2383 node-negative (pN0), 107 isolated tumour cells (pN0(i+), 123 micrometastases (pN1mi) and 756 macrometastases (pN1)) was analysed. The 5-year cause-specific and event-free survival was worse for pN1mi and pN1 patients than for pN0 patients. There was no difference in survival between pN0(i+) and pN0 patients.Tumour and SLN characteristics in 869 SLN-positive patients were compared between those with and without non-SLN metastases, and the Tenon score was calculated. The risk of non-SLN metastases was higher in case of SLN macrometastases (compared with micrometastases), a high positive/total SLN ratio and Elston grade 3 tumours, and increased with increasing tumour size. The area under the curve (AUC) for the Tenon score was 0.65, and the test thus performed inadequately in this population.In conclusion, despite the risk of false negativity, SLNB with omission of ALND in SLN-negative patients appears to be safe even in the long term. The presence of micrometastases is of prognostic importance and should entail adjuvant treatment. The need for ALND in patients with SLN micro- and even macrometastases has been questioned, but the occurrence of non-SLN metastases is hard to predict, and strong evidence for the safe omission of ALND is lacking.
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| 2. |
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| 3. |
- Carlander, Johan, 1971-
(författare)
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Energy based surgical instruments : With particular focus on collateral thermal injury
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Iatrogenic post-operative nerve dysfunction is a significant problem in many areas of surgery and can be caused by collateral thermal injury from activation of energy based surgical devices (EBD).The aims of this thesis were to: create an animal model in order to compare mono- and bipolar electrosurgery (ES) and an ultrasonic dissection (UD) with regard to collateral thermal nerve injury, and with data of a national multicenter register to study the use of EBD and their potential effects on operation time and complication rates in thyroid surgery.urgical devices (EBD).Material and Methods: The biceps femoris muscle of 104 anesthetized rats was cut in a standard manner adjacent to the sciatic nerve using clinical relevant settings of mono- and bipolar ES and UD. The sciatic nerve was stimulated supramaximally and the electromyographic (EMG) potential recorded before and after each experiment. Nerve dysfunction was defined as > 10% reduction of the evoked EMG potential. In Paper II and III temperature was measured before, during and after instrument activation. The sciatic nerves were coded and examined blinded with light (LM) and electron microscopy (EM). Advanced temperature measurements were conducted in Paper II and III. In Paper IV, the use of EBD was specifically registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) during one year and 1297 patients were included. Operation time, recurrent laryngeal nerve (RLN) injury, post-operative hypoparathyroidism and the use of topical haemostatic agents were compared between bipolar ES, electric vessel sealing (EVS) and UD. Clamp and Tie technique (C-A-T) being without thermal risk constituted the control group.Results: In Paper I the EMG potential was significantly more frequent reduced in the monopolar and bipolar ES group compared to the UD group and LM showed significantly less nerve damage in the UD group. In Paper II exact temperature measurements was possible with thermoelectric micros sensors and the thermal dose was significantly less and with less variation for the UD compared to the bipolar ES. Similar to the Paper I the EMG potential was significantly more frequent reduced in the ES group. Moderate and severe morphological damage was significantly less common in the UD group compared to monopolar ES. We found no statistical correlation between the highest temperatures/doses and the degree of morphological damage or functional loss. In Paper III the temperature increase was significantly less and with shorter duration in the UD group, compared to bipolar ES. LM and EM demonstrated loss of density in the myelin sheet only in a small number of nerves in all groups after instrument activation 1 mm from the nerve.In Paper IV, operation time was significantly shorter in the UD group and significantly longer in the EVS and bipolar ES group, compared to C-A-T. Postoperative hypoparathyroidism with need for Calcium treatment at discharge and at 6 weeks was significantly higher with ES instruments compared to UD. The incidence of reported RLN injury was 2.5% at 6 weeks postoperatively without statistical differences between the groups. Topical haemostatic agents were more frequently used in the EBD groups compared to C-A-T.Conclusion: The experimental Papers (I-III) demonstrated a lower risk of adverse collateral thermal nerve injury with activation of the mechanical UD technique compared to ES techniques. In the nationwide multicenter register Paper (IV), the use of UD shortened end EVS increased operation time compared to the low cost C-A-T. The UD instruments had a lower risk of hypoparathyroidism than electrosurgery.
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| 4. |
- de Boniface, Jana, 1971-
(författare)
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Sentinel Node Biopsy in Breast Cancer : Clinical and Immunological Aspects
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The most important prognostic factor in breast cancer is the axillary lymph node status. The sentinel node biopsy (SNB) is reported to stage the axilla with an accuracy > 95 % in early breast cancer. Tumour-related perturbation of T-cell function has been observed in patients with malignancies, including breast cancer. The down-regulation of the important T-cell activation molecules CD3-ζ and CD28 may cause T-cell dysfunction, anergy, tolerance and deletion.The expression of CD3-ζ and CD28 was evaluated in 25 sentinel node biopsies. The most pronounced down-regulation was seen in the paracortical area, where the best agreement between both parameters was observed. CD28 expression was significantly more suppressed in CD4+ than in CD8+ T-cells.From the Swedish sentinel node database, 109 patients with breast cancer > 3 cm planned for both SNB and a subsequent axillary dissection were identified. The false negative rate (FNR) was 12.5%. Thirteen cases of tumour multifocality were detected on postoperative pathology. The FNR in this subgroup was higher (30.8%) than in patients with unifocal disease (7.8%; P = 0.012).From the Swedish SNB multicentre cohort trial, 2246 sentinel node-negative patients who had not undergone further axillary surgery were selected for analysis. After a median follow-up time of 37 months (range 0-75), 13 isolated axillary recurrences (13/2246; 0.6%) were found. In another 14 cases, local or distant failure preceded or coincided with axillary relapse (27/2246; 1.2%). In conclusion, the immunological analysis of the sentinel node might provide valuable prognostic information and aid selection of patients for immunotherapy. SNB is encouraged in breast cancer larger than 3 cm, if no multifocal growth pattern is present. The axillary recurrence rate after a negative SNB in Sweden is in accordance with international figures. However, a longer follow-up is mandatory before the true failure rate of the SNB can be determined.
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| 5. |
- Eklund, Arne, 1957-
(författare)
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Laparoscopic or Open Inguinal Hernia Repair - Which is Best for the Patient?
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inguinal hernia repair is the most common operation in general surgery. Its main challenge is to achieve low recurrence rates. With the introduction of mesh implants, first in open and later in laparoscopic repair, recurrence rates have decreased substantially. Therefore, the focus has been shifted from clinical outcome, such as recurrence, towards patient-experienced endpoints, such as chronic pain. In order to compare the results of open and laparoscopic hernia repair, a randomised multicentre trial - the Swedish Multicentre trial of Inguinal hernia repair by Laparoscopy (SMIL) - was designed by a study group from 11 hospitals. Between November 1996 and August 2000, 1512 men aged 30-70 years with a primary inguinal hernia were randomised to either laparoscopic (TEP, Totally ExtraPeritoneal) or open (Lichtenstein) repair. The primary endpoint was recurrence at five years. Secondary endpoints were short-term results, frequency of chronic pain and a cost analysis including complications and recurrences up to five years after surgery. In total, 1370 patients, 665 in the TEP and 705 in the Lichtenstein group, underwent operation. With 94% of operated patients available for follow-up after 5.1 years, the recurrence rate was 3.5% in the TEP and 1.2% in the Lichtenstein group. Postoperative pain was lower in the TEP group up to 12 weeks after operation, resulting in five days less sick leave and 11 days shorter time to full recovery. Patients in the TEP group had a slightly increased risk of major complications. Chronic pain was reported by 9-11% of patients in the TEP and 19-25% in the Lichtenstein group at the different follow-up points. Hospital costs for TEP were higher than for Lichtenstein, while community costs were lower due to shorter sick leave. By avoiding disposable laparoscopic equipment, the cost for TEP would be almost equal compared with Lichtenstein. In conclusion, both TEP and Lichtenstein repair have advantages and disadvantages for the patient. Depending on local resources and expertise both methods can be used and recommended for primary inguinal hernia repair.
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| 6. |
- Frisk, Jessica, 1971-
(författare)
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Acupuncture treatment for hot flushes in women with breast cancer and men with prostate cancer
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The group of women and men with a history of cancer and distressing hot flushes and sweating is growing. The flushes negatively affect Health Related Quality of Life (HRQoL), perhaps partially by disturbing sleep. Treatments that are effective, tolerable and safe need to be developed. There are a number of treatment alternatives that are often not very effective or associated with more or less serious side-effects. Based on theories on the mechanisms behind hot flushes and acupuncture, treatment with acupuncture has been tried in menopausal women with hot flushes and in a few studies in women with breast cancer (BCa).Aim: The general aim of the research leading to this thesis was to evaluate the effect of acupuncture on hot flushes, HRQoL and sleep in men with prostate cancer (PCa) and women with BCa. To evaluate the effect in women with BCa of 12 weeks of electrostimulated acupuncture (EA) and two years of hormone therapy (HT) on number of, and distress caused by, hot flushes, and on HRQoL and sleep. To evaluate whether acupuncture therapy could be used to treat hot flushes in men with PCa treated with castration therapy, and then to evaluate in men with PCa and hot flushes the effect of 12 weeks of traditional acupuncture (TA) or EA on number of, and distress caused by, hot flushes and on urinary excretion of CGRP, HRQoL and sleep.Subjects and methods: Forty-five women with a history of BCa were randomized to oral HT for two years or EA for 12 weeks and were followed up till two years after start of therapy. Thirty-eight men with PCa and hot flushes were treated with acupuncture. Seven men were treated with EA for 10 to 12 weeks in a pilot study. After positive results from this study 31 men were randomized between EA and TA for 12 weeks and followed up till nine months after end of treatment. Hot flushes, HRQoL and sleep were monitored by means of log books and validated questionnaires.Results: The pilot study showed that 10 to 12 weeks of EA in men with PCa reduced number of hot flushes to below 50% of baseline with persistent effects at a follow up three months later. The two randomized studies showed that treatment with acupuncture in women with a history of BCa, and men with PCa was associated with a decrease in both the number of and distress caused by hot flushes by at least 50%. HT almost eliminated the hot flushes. There was no difference in reduction of hot flushes between men receiving EA or TA. Reduction of the number of hot flushes and distress caused by hot flushes probably leads to decreased disturbances at night, and was associated in women with a significant improvement in HRQoL and sleep variables. The improvement in HRQoL was as great in women treated with EA as in women receiving HT although the latter group had a more substantial reduction in number of flushes than the EA group suggesting that EA might have other effects in addition to those on hot flushes. In the men HRQoL did not change significantly. We saw very few and non-serious side-effects in the acupuncture groups and no signs that acupuncture activated the cancer or ovarian/testicular function.Conclusions: Acupuncture reduced the number of hot flushes and distress caused by hot flushes with at least 50% in women and men with hot flushes and a cancer disease and also improved HRQoL and sleep at least in women. Acupuncture should be further evaluated in these patient groups and could be a treatment alternative in patients with troublesome symptoms.
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| 7. |
- Granstam Björneklett, Helena, 1962-
(författare)
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Support Group Intervention in Primary Breast Cancer : Health-Related Quality of Life, with Special Reference to Anxiety, Depression and Fatigue
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate in a (RCT) the effect of support group intervention in women with primary breast cancer in the short term, and with a long-term follow-up. Women with primary breast cancer were randomized between April 2002 and November 2007 and stratified according to adjuvant treatment with chemotherapy. Of 382 eligible patients, 191+191 patients were randomized to intervention and control groups respectively. Control patients were subjected to standard follow-up procedures. Patients in the intervention group received support intervention at the Foundation of Lustgården Mälardalen during one week followed by four days of follow-up two months later. Patients in intervention and control groups filled in questionnaires at baseline, after 2, 6 and 12 months and in the long-term follow-up after a mean of 6.5 years. In paper I, we studied the effect of the intervention on anxiety and depression measured by the HAD scale and we could show that a significantly lower proportion of women in the intervention group had high anxiety scores compared with women in the control group after 12 months; however, the proportion of women with high depression scores were unaffected. In paper II, we studied the effect of the intervention on fatigue and health-related quality of life (HRQoL) measured by the Norwegian version of the fatigue questionnaire (FQ) and EORTC-QLQ 30 and BR 23.We could not demonstrate any significant effect of the intervention. In paper III, we studied the effect of the intervention on sick-leave, healthcare utilization and the effect of the intervention in economic terms. We used a specially formulated questionnaire. There was a trend towards longer sick leave and more health-care utilization in the intervention group. The difference in total costs was statistically significantly higher in the intervention group after 12 months (p= 0.0036). In paper IV, we studied the long-term effects of the support intervention on anxiety, depression, fatigue and HRQoL. We could show a significant effect of the intervention on cognitive function, body image, future perspective and fatigue, the largest effect was seen among women who received chemotherapy; however, no effects on anxiety and depression were demonstrated.
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| 8. |
- Nilsson, Cecilia, 1971-
(författare)
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Characterization of Male Breast Cancer : From Molecule to Clinical Outcome
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate different aspects of male breast cancer (MBC), and to compare these with findings in female breast cancer (FBC). In paper I, a population–based study was performed to investigate possible differences in treatment and outcome between MBC and FBC patients. MBC and FBC presented with a similar distribution of stage. Although no differences in primary treatment strategy were demonstrated, MBC patients had significantly poorer overall and relative survival, indicating a more aggressive disease. Paper II aimed to assess the value of clinicopathological factors and molecular subtypes in MBC. One hundred and ninety-seven MBC tumors were characterized using immunohistochemistry (IHC) and the findings were correlated to outcome. Lymph node positivity, larger tumor size and ER-negativity were independent risk factors for breast cancer death. Tumor grade, HER2, Ki 67 or IHC classification into molecular subtypes did not demonstrate any prognostic information. In paper III, the same patient material as in paper II was used for evaluation of proliferation markers. High levels of cyclin A and cyclin B expression and an elevated mitotic count were predictive of breast cancer death. Ki-67 was re-evaluated using different cut-offs, but no prognostic value could be demonstrated. Contrarily, overexpression of cyclin D1 was associated with a lower risk of breast cancer death. In papers IV-V, the molecular background of MBC tumors was investigated. Global GEX analyses were performed and two novel subgroups of MBC tumors were identified; luminal M1 and luminal M2. When comparing the degree of similarity with the “intrinsic” subtypes in FBC tumors, more than half of the MBC tumors remained unclassified. Comparative genomic hybridization was used to investigate DNA aberrations. Two MBC subgroups were identified, of which one did not resemble any of the female subgroups. In both studies on the molecular level, a majority of patients were classified into the subgroup with a more aggressive tumor behavior. In conclusion, MBC seems to be a unique tumor entity. The established molecular subtypes in FBC are not applicable in MBC. Other prognostic profiles, specific for MBC, need to be identified.
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| 9. |
- Söderström, Lisa, 1982-
(författare)
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Nutritional Screening of Older Adults : Risk Factors for and Consequences of Malnutrition
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims The overall aim of this thesis was to extend current knowledge about the prevalence of malnutrition, to identify possible risk factors for development of malnutrition, and to describe the consequences of malnutrition in relation to all-cause and cause-specific mortality among older adults admitted to hospital.Methods The prevalence of malnutrition was estimated in a cohort of 1771 older adults (≥65 years) who were admitted to a Swedish hospital during 2008–2009 (15 months) and screened for malnutrition using the Mini Nutritional Assessment (MNA) instrument. Possible risk factors for malnutrition were recorded during the hospital stay (Study I). Dietary intake 10 years earlier (in 1997) was collected for 725 of these older adults (Study II). All-cause (Study III) and cause-specific (Study IV) mortality were followed up after medians of 3.5 and 5.1 years, respectively, for 1767 of the participants.Results The prevalence of malnutrition was 9.4% while 55.1% were at risk of malnutrition. Risk factors for malnutrition was an overnight fast >11 hours, <4 eating episodes a day, and not cooking independently. In middle-aged and older adults with a body mass index <25 kg/m2 in 1997, the risk of malnutrition increased for each additional percentage point of energy from total, saturated and monounsaturated fat at follow-up after 10 years. Malnourished older adults had almost four times higher risk of death during follow-up, while those at risk of malnutrition had a 56% higher risk, compared to well-nourished. Furthermore, well-nourished older adults had consistently lower risk of death, regardless of the cause of death.Conclusions Only 35.5% of older adults admitted to hospital were well-nourished. The identified risk factors could be used in interventions aimed at preventing malnutrition. Normal-weight and underweight middle-aged and older adults should consider limiting the intake of total fat and/or improve the quality of the fat in the diet in order to decrease the risk of becoming malnourished later in life. Malnutrition and risk of malnutrition were associated with increased overall and cause-specific mortality. These relationships emphasize the need for nutritional screening to identify individuals who may require nutritional support in order to avoid preterm death.
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