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00007632nam a22005173a 4500
008080901s2017 xx |||| sm |0|| 0|eng d
020 a 9789176855546
024a 10.3384/diss.diva-1374742 doi
024a urn:nbn:se:liu:diva-1374742 urn
040 a (SwePub)liu
042 9 SwePub
072 7a vet2 swepub-contenttype
072 7a dok2 swepub-publicationtype
072 7a vet2 swepub-contenttype
100a Aljabery, Firas,u Linköpings universitet, Institutionen för klinisk och experimentell medicin, Linköpings universitet, Medicinska fakulteten4 aut0 (SwePub:)
2451 0a Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
260 a Linköping :b Linköping University Electronic Press,c 2017
300 a 79s.
490a Linköping University Medical Dissertations,x 0345-0082
500 a Published
500 a 1
5208 enga <p><strong>Aim: </strong>To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.</p><p><strong>Patients and Methods: </strong>We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.</p><p><strong>Results: </strong>Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.</p><p><strong>Conclusion: </strong>PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.</p>
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi2 hsv//swe0 (SwePub)30203
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology2 hsv//eng0 (SwePub)30203
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Urologi och njurmedicin2 hsv//swe0 (SwePub)30214
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Urology and Nephrology2 hsv//eng0 (SwePub)30214
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Klinisk laboratoriemedicin2 hsv//swe0 (SwePub)30223
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Clinical Laboratory Medicine2 hsv//eng0 (SwePub)30223
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kirurgi2 hsv//swe0 (SwePub)30212
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Surgery2 hsv//eng0 (SwePub)30212
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Gastroenterologi2 hsv//swe0 (SwePub)30213
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Gastroenterology and Hepatology2 hsv//eng0 (SwePub)30213
700a Gimm, Oliver,c Professor,d 1967-,u Linköpings universitet, Avdelningen för Kirurgi, Ortopedi och Onkologi, Linköpings universitet, Medicinska fakulteten, Region Östergötland, Kirurgiska kliniken US4 ths0 (SwePub:liu)
700a Jahnson, Staffan,d 1950-,u Linköpings universitet, Avdelningen för Kirurgi, Ortopedi och Onkologi, Linköpings universitet, Medicinska fakulteten, Region Östergötland, Urologiska kliniken i Östergötland4 ths0 (SwePub:liu)
700a Shabo, Ivan,c Dr.,u Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institution, Stockholm4 ths0 (SwePub:liu)
700a Olsson, Hans,c Dr.,u Linköpings universitet, Avdelningen för inflammationsmedicin, Linköpings universitet, Medicinska fakulteten, Region Östergötland, Klinisk patologi och klinisk genetik4 ths0 (SwePub:liu)
700a Söderkvist, Peter,d 1953-,u Linköpings universitet, Avdelningen för cellbiologi, Linköpings universitet, Medicinska fakulteten, Region Östergötland, Klinisk patologi och klinisk genetik4 ths0 (SwePub:liu)
700a Peeker, Ralph,c Professor,u Division of Urology, Sahlgrenska University Hospital and University of Gothenburg, Sweden4 opn0 (SwePub:)
8564 8u https://doi.org/10.3384/diss.diva-137474
8564 8u http://liu.diva-portal.org/smash/get/diva2:1096107/FULLTEXT01.pdf
8564 8u http://liu.diva-portal.org/smash/get/diva2:1096107/COVER01.pdf
8564 8u http://liu.diva-portal.org/smash/get/diva2:1096107/PREVIEW01.jpg
8564 0u http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-137474y Till lärosätets (liu) databasx freex lärosäteslänk

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