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Sweden: cancer statistics from IARC GlobalCan (2012)

Population in 2012: 9.5m
People newly diagnosed with cancer (excluding NMSC) / yr: 50,500
Age-standardised rate, incidence per 100,000 people/yr: 270.0
Risk of getting cancer before age 75:27.8%
People dying from cancer /yr: 22,100

Menu: Swedish Cancer Resources

Swedish Cancer Organisations
Cancer Centres in Sweden
Latest Research Publications from Sweden

Swedish Cancer Organisations (16 links)

Cancer Centres in Sweden (6 links)

Latest Research Publications from Sweden

Bockhorn M, Uzunoglu FG, Adham M, et al.
Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS).
Surgery. 2014; 155(6):977-88 [PubMed] Related Publications
BACKGROUND: This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability.
METHODS: An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer.
RESULTS: The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers.
CONCLUSION: Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

Related: Cancer of the Pancreas Pancreatic Cancer
Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Juul T, Ahlberg M, Biondo S, et al.
Low anterior resection syndrome and quality of life: an international multicenter study.
Dis Colon Rectum. 2014; 57(5):585-91 [PubMed] Related Publications
BACKGROUND: An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to 90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome.
OBJECTIVE: The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer.
DESIGN: The study was designed as an international cross-sectional study involving 5 centers in 4 European countries.
PATIENTS: All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery.
INTERVENTIONS: The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30.
MAIN OUTCOME MEASURES: Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea.
RESULTS: A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation.
LIMITATIONS: The cross-sectional design prevents an evaluation of causality.
CONCLUSIONS: The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.
1Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark 2Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden 3General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, Barcelona, Spain 4Hospital Valle de Hebron, Universitat Autono...

Pettersson A, Graff RE, Ursin G, et al.
Mammographic density phenotypes and risk of breast cancer: a meta-analysis.
J Natl Cancer Inst. 2014; 106(5) [PubMed] Related Publications
BACKGROUND: Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk.
METHODS: We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant.
RESULTS: Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity < .01) for postmenopausal women.
CONCLUSIONS: The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

Related: Breast Cancer
Affiliations of authors: Department of Epidemiology (AP, REG, RMT), and Department of Biostatistics (BAR), Harvard School of Public Health, Boston, MA; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway (GU); Department of Preventive Medicine, Keck School...
Research funded by:

Tertipis N, Villabona L, Nordfors C, et al.
HLA-A*02 in relation to outcome in human papillomavirus positive tonsillar and base of tongue cancer.
Anticancer Res. 2014; 34(5):2369-75 [PubMed] Related Publications
BACKGROUND/AIM: Patients with human papillomavirus (HPV)-positive tonsillar and base of tongue cancer have a better outcome than those with corresponding HPV-negative tumors (80% vs. 40% 5-year disease free survival with conventional radiotherapy). They should not all need chemoradiotherapy, but before tapering treatment, more markers are needed to predict treatment response. In the present study, human leukocyte antigen (HLA) - HLA-A*02 was analyzed with HPV as a prognostic factor for tonsillar and base of tongue cancer.
PATIENTS AND METHODS: Pre-treatment biopsies, previously tested for HPV DNA, from 425 patients diagnosed with tonsillar and base of tongue cancer between 2000-2009 at the Karolinska University Hospital were examined for HLA-A*02.
RESULTS: HLA-A*02 was present in 144/305 (47.2%) of the HPV-positive and 63/120 (52.8%) of the HPV-negative tumours. Among 383 patients treated with curative intent, absence of HLA-A*02 was correlated with increased disease-free survival in the HPV-positive (p=0.016), but not in the HPV-negative group.
CONCLUSION: Absence of HLA-A*02 correlated with better disease-free survival for patients with HPV-positive tonsillar and base of tongue cancer.
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:01 Karolinska University Hospital, 171 76 Stockholm, Sweden.

Pauly F, Smedby KE, Jerkeman M, et al.
Identification of B-cell lymphoma subsets by plasma protein profiling using recombinant antibody microarrays.
Leuk Res. 2014; 38(6):682-90 [PubMed] Related Publications
B-cell lymphoma (BCL) heterogeneity represents a key issue, often making the classification and clinical management of these patients challenging. In this pilot study, we outlined the first resolved view of BCL disease heterogeneity on the protein level by deciphering disease-associated plasma biomarkers, specific for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, using recombinant antibody microarrays targeting mainly immunoregulatory proteins. The results showed the BCLs to be heterogeneous, and revealed potential novel subgroups of each BCL. In the case of diffuse large B-cell lymphoma, we also indicated a link between the novel subgroups and survival.
Department of Immunotechnology, Lund University, Lund, Sweden; CREATE Health, Lund University, Lund, Sweden.

Tuominen R, Jönsson G, Enerbäck C, et al.
Investigation of a putative melanoma susceptibility locus at chromosome 3q29.
Cancer Genet. 2014; 207(3):70-4 [PubMed] Related Publications
Malignant melanoma, the most fatal form of skin cancer, is currently increasing in incidence in many populations. Approximately 10% of all cases occur in families with an inherited predisposition for melanoma. In Sweden, only a minor portion of such melanoma families carry a mutation in the known melanoma gene CDKN2A, and there is a need to identify additional melanoma susceptibility genes. In a recently performed genome-wide linkage screen, novel loci with suggestive evidence of linkage to melanoma were detected. In this study, we have further analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected family members from 42 melanoma-prone families were genotyped for 34 genetic markers. In a pooled linkage analysis of all 42 families, we detected significant evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score of 3.1 with 83% of the families contributing to the linkage score. The minimum critical region of linkage (defined by a 1LOD score support interval) maps to chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified genes. Sequence variants within this region have previously been associated with cancer susceptibility. This study reports the presence of a putative novel melanoma susceptibility locus in the Swedish population, a finding that needs to be replicated in an independent study on other individuals with familial melanoma. Sequencing of genes in the region may identify novel melanoma-associated mutations.

Related: Chromosome 3 Melanoma Skin Cancer
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

Dragomir A, de Wit M, Johansson C, et al.
The role of SATB2 as a diagnostic marker for tumors of colorectal origin: Results of a pathology-based clinical prospective study.
Am J Clin Pathol. 2014; 141(5):630-8 [PubMed] Related Publications
OBJECTIVES: Immunohistochemistry is an important extension to clinical information and morphology, and prevails as an invaluable tool for establishing a correct cancer diagnosis in clinical diagnostic pathology. The applicability of immunohistochemistry is limited by the availability of validated cell- and cancer-type specific antibodies, rendering an unmet need to discover, test, and validate novel markers. The SATB2 protein is selectively expressed in glandular cells from the lower gastrointestinal tract and expression is retained in a large majority of primary and metastatic colorectal cancers.
METHODS: We analyzed the expression of SATB2 in all clinical cases (n = 840), in which immunohistochemistry for detection of CK20 was deemed necessary for a final diagnosis.
RESULTS: SATB2 showed a high sensitivity (93%) and specificity (77%) to determine a cancer of colorectal origin and in combination with CK7 and CK20, the specificity increased to 100%.
CONCLUSIONS: We conclude that SATB2 provides a new and advantageous supplement for clinical differential diagnostics.

Related: Colorectal (Bowel) Cancer
Dept of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden;

Dittrich C, Papai-Szekely Z, Vinolas N, et al.
A randomised phase II study of pemetrexed versus pemetrexed+erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer.
Eur J Cancer. 2014; 50(9):1571-80 [PubMed] Related Publications
INTRODUCTION: Pemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed+erlotinib in patients with advanced non-squamous NSCLC.
METHODS: NSCLC stage III-IV patients who failed one prior platinum-based chemotherapy regimen, ≥ 1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status ≤ 2 were eligible. Patients received pemetrexed 500 mg/m(2) with vitamin B12 and folic acid q3w alone or combined with erlotinib 150 mg daily. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), time-to-treatment failure (TTTF), response and toxicity.
RESULTS: Of 165 randomised non-squamous patients, 159 were treated (pemetrexed: 83; pemetrexed+erlotinib: 76). The median PFS (months; 95% CI) was 2.89 (1.94, 3.38) for pemetrexed versus 3.19 (2.86, 4.70) for pemetrexed+erlotinib (hazard ratio [HR] 0.63; 95% CI: (0.44, 0.90); P = 0.0047). The median OS (months; 95% CI) was 7.75 (5.29, 10.41) for pemetrexed versus 11.83 (8.18, 16.66) for pemetrexed+erlotinib (HR: 0.68; 95% CI: 0.46, 0.98; P = 0.019). The median TTTF (months: 95% CI) was 2.4 (1.74, 2.99) for pemetrexed versus 3.0 (2.23, 4.07) for pemetrexed+erlotinib (HR 0.64; 95% CI: 0.46, 0.89; P = 0.0034). One patient died in pemetrexed+erlotinib arm due to febrile neutropenia. Grades 3/4 drug-related toxicities (in ≥ 5% of patients) in pemetrexed/pemetrexed+erlotinib were febrile neutropenia (2.4%/10.5%), diarrhoea (1.2%/5.3%), rash (1.2%/9.2%); anaemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%).
CONCLUSIONS: Pemetrexed+erlotinib treatment significantly improved PFS, OS and TTTF in 2nd line non-squamous NSCLC and was associated with an increase in grade 3/4 toxicities compared with pemetrexed alone.

Related: Non-Small Cell Lung Cancer Lung Cancer Pemetrexed Erlotinib (Tarceva)
LBI-ACR VIEnna and ACR-ITR VIEnna, Kaiser Franz Josef-Spital, Vienna, Austria. Electronic address:

Gad H, Koolmeister T, Jemth AS, et al.
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool.
Nature. 2014; 508(7495):215-21 [PubMed] Related Publications
Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

Related: Cancer Prevention and Risk Reduction
1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2].

Eriksson H, Lyth J, Månsson-Brahme E, et al.
Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from Sweden.
J Clin Oncol. 2014; 32(13):1356-64 [PubMed] Related Publications
PURPOSE: To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM).
METHODS: This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based registers followed up through 2012.
RESULTS: After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001), suggesting a residual adverse effect on survival not accounted for by these parameters.
CONCLUSION: In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.

Related: Melanoma Skin Cancer
Hanna Eriksson, Eva Månsson-Brahme, Margareta Frohm-Nilsson, and Johan Hansson, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm; Johan Lyth and Christer Lindholm, Regional Cancer Center Southeast, Linköping University Hospital; Johan Lyth and John Carstensen, Link&#...

Carlsson S, Assel M, Sjoberg D, et al.
Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study.
BMJ. 2014; 348:g2296 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To determine the relative risks of prostate cancer incidence, metastasis, and mortality associated with screening by serum prostate specific antigen (PSA) levels at age 60.
DESIGN: Population based cohort study.
SETTING: General male population of Sweden taking part in a screening trial in Gothenburg or participating in a cardiovascular study, the Malmö Preventive Project.
PARTICIPANTS: The screened group consisted of 1756 men aged 57.5-62.5 participating in the screening arm of the Gothenburg randomized prostate cancer screening trial since 1995. The unscreened group consisted of 1162 men, born in 1921, participating in the Malmö Preventive Project, with PSA levels measured retrospectively in stored blood samples from 1981.
INTERVENTION: PSA screening versus no screening.
MAIN OUTCOME MEASURES: Incidence rate ratios for the effect of screening on prostate cancer diagnosis, metastasis, and death by PSA levels at age 60.
RESULTS: The distribution of PSA levels was similar between the two cohorts. Differences in benefits by baseline PSA levels were large. Among men with baseline levels measured, 71.7% (1646/2295) had a PSA level <2 ng/mL. For men aged 60 with PSA level <2 ng/mL, there was an increase in incidence of 767 cases per 10,000 without a decrease in prostate cancer mortality. For men with PSA levels ≥ 2 ng/mL, the reduction in cancer mortality was large, with only 23 men needing to be screened and six diagnosed to avoid one prostate cancer death by 15 years.
CONCLUSIONS: The ratio of benefits to harms of PSA screening varies noticeably with blood PSA levels at age 60. For men with a PSA level <1 ng/mL at age 60, no further screening is recommended. Continuing to screen men with PSA levels >2 ng/mL at age 60 is beneficial, with the number needed to screen and treat being extremely favourable. Screening men with a PSA level of 1-2 ng/mL is an individual decision to be based on a discussion between patient and doctor.

Related: Cancer Screening and Early Detection Prostate Cancer
Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden.
Research funded by:

Sörensen J, Sandberg D, Sandström M, et al.
First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule.
J Nucl Med. 2014; 55(5):730-5 [PubMed] Related Publications
UNLABELLED: The expression status of human epidermal growth factor receptor type 2 (HER2) predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a small reengineered Affibody molecule targeting a unique epitope of the HER2 receptor, not occupied by current therapeutic agents. This study evaluated the distribution, safety, dosimetry, and efficacy of (111)In-ABY-025 for determining the HER2 status in metastatic breast cancer.
METHODS: Seven patients with metastatic breast cancer and HER2-positive (n = 5) or -negative (n = 2) primary tumors received an intravenous injection of approximately 100 μg (∼ 140 MBq) of (111)In-ABY-025. Planar γ-camera imaging was performed after 30 min, followed by SPECT/CT after 4, 24, and 48 h. Blood levels of radioactivity, antibodies, shed serum HER2, and toxicity markers were evaluated. Lesional HER2 status was verified by biopsies. The metastases were located by (18)F-FDG PET/CT 5 d before (111)In-ABY-025 imaging.
RESULTS: Injection of (111)In-ABY-025 yielded a mean effective dose of 0.15 mSv/MBq and was safe, well tolerated, and without drug-related adverse events. Fast blood clearance allowed high-contrast HER2 images within 4-24 h. No anti-ABY-025 antibodies were observed. When metastatic uptake at 24 h was normalized to uptake at 4 h, the ratio increased in HER2-positive metastases and decreased in negative ones (P < 0.05), with no overlap and confirmation by biopsies. In 1 patient, with HER2-positive primary tumor, (111)In-ABY-025 imaging correctly suggested a HER2-negative status of the metastases. The highest normal-tissue uptake was in the kidneys, followed by the liver and spleen.
CONCLUSION: (111)In-ABY-025 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic breast cancer, regardless of ongoing HER2-targeted antibody treatment.

Related: Breast Cancer
Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden.

Kotti A, Holmqvist A, Albertsson M, Sun XF
SPARCL1 expression increases with preoperative radiation therapy and predicts better survival in rectal cancer patients.
Int J Radiat Oncol Biol Phys. 2014; 88(5):1196-202 [PubMed] Related Publications
PURPOSE: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT.
METHODS AND MATERIALS: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry.
RESULTS: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569).
CONCLUSIONS: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.
Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, County Council of Östergötland, University of Linköping, Linköping, Sweden. Electronic address:

Delahunt B, Srigley JR, Montironi R, Egevad L
Advances in renal neoplasia: recommendations from the 2012 International Society of Urological Pathology Consensus Conference.
Urology. 2014; 83(5):969-74 [PubMed] Related Publications
The International Society of Urological Pathology (ISUP) 2012 Consensus Conference made recommendations regarding the classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. There was consensus that 5 entities should be recognized as novel tumors: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell papillary RCC, microphthalmia transcription factor-family translocation RCC [in particular t(6; 11) RCC], and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, 3 rare epithelial carcinomas were considered emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC, and anaplastic lymphoma kinase translocation RCC. There were also a number of suggested modifications to existing World Health Organization 2004 categories, with the new classification to be known as the ISUP Vancouver Classification. Tumor morphotype, sarcomatoid/rhabdoid differentiation, and tumor necrosis were identified as significant prognostic parameters for RCC. The ISUP Grading System was accepted with grades 1-3 of clear cell and papillary RCC being based on nucleolar prominence, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed that chromophobe RCC should not be graded. Consensus guidelines were formulated for specimen handling, and it was agreed that renal sinus invasion is present when tumor is in direct contact with fat or loose connective tissue of the sinus or if there is involvement of endothelial-lined spaces within the renal sinus, regardless of the size. The role of biomarkers in the diagnosis and assessment of prognosis of renal tumors was considered, and panels of immunohistochemical markers were identified for use in specific differential diagnostic scenarios.

Related: Kidney Cancer
Department of Pathology and Molecular Medicine, Wellington School of Medicine, University of Otago, Wellington, New Zealand. Electronic address:

Nord KH, Lilljebjörn H, Vezzi F, et al.
GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.
Nat Genet. 2014; 46(5):474-7 [PubMed] Related Publications
Glutamate receptors are well-known actors in the central and peripheral nervous systems, and altered glutamate signaling is implicated in several neurological and psychiatric disorders. It is increasingly recognized that such receptors may also have a role in tumor growth. Here we provide direct evidence of aberrant glutamate signaling in the development of a locally aggressive bone tumor, chondromyxoid fibroma (CMF). We subjected a series of CMFs to whole-genome mate-pair sequencing and RNA sequencing and found that the glutamate receptor gene GRM1 recombines with several partner genes through promoter swapping and gene fusion events. The GRM1 coding region remains intact, and 18 of 20 CMFs (90%) showed a more than 100-fold and up to 1,400-fold increase in GRM1 expression levels compared to control tissues. Our findings unequivocally demonstrate that direct targeting of GRM1 is a necessary and highly specific driver event for CMF development.

Related: Bone Cancers FISH Signal Transduction
Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.

Thiel T, Ryk C, Chatzakos V, et al.
Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells.
Cancer Lett. 2014; 348(1-2):119-25 [PubMed] Related Publications
The anti-tumour mechanisms following Bacillus Calmette-Guérin (BCG) treatment of bladder-cancer remain largely unknown. Previous studies have shown involvement of nitric-oxide (NO) formation in the BCG-mediated effect. We analyzed the effects of macrophage secreted factors (MSFs) from BCG-stimulated RAW264.7 cells on the bladder-cancer cell line MBT2. Direct treatment with BCG did not induce NO in MBT2-cells whereas supernatant from BCG-stimulated macrophages increased NOS2 mRNA and protein expression, NO concentrations and cell-death. Blocking NO-synthesis with the NOS-inhibitor L-NAME did not affect levels of cell-death suggesting cytotoxic pathways involving other signalling molecules than NO. Several such candidate genes were identified in a microarray.

Related: Signal Transduction Bladder Cancer Bladder Cancer - Molecular Biology
Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Koch S, van Meeteren LA, Morin E, et al.
NRP1 presented in trans to the endothelium arrests VEGFR2 endocytosis, preventing angiogenic signaling and tumor initiation.
Dev Cell. 2014; 28(6):633-46 [PubMed] Related Publications
Neuropilin 1 (NRP1) modulates angiogenesis by binding vascular endothelial growth factor (VEGF) and its receptor, VEGFR2. We examined the consequences when VEGFR2 and NRP1 were expressed on the same cell (cis) or on different cells (trans). In cis, VEGF induced rapid VEGFR2/NRP1 complex formation and internalization. In trans, complex formation was delayed and phosphorylation of phospholipase Cγ (PLCγ) and extracellular regulated kinase 2 (ERK2) was prolonged, whereas ERK1 phosphorylation was reduced. Trans complex formation suppressed initiation and vascularization of NRP1-expressing mouse fibrosarcoma and melanoma. Suppression in trans required high-affinity, steady-state binding of VEGF to NRP1, which was dependent on the NRP1 C-terminal domain. Compatible with a trans effect of NRP1, quiescent vasculature in the developing retina showed continuous high NRP1 expression, whereas angiogenic sprouting occurred where NRP1 levels fluctuated between adjacent endothelial cells. Therefore, through communication in trans, NRP1 can modulate VEGFR2 signaling and suppress angiogenesis.

Related: Angiogenesis and Cancer VEGFA
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory and Science for Life Laboratory, Uppsala University, Dag Hammarskjöldsväg 20, 75185 Uppsala, Sweden.

Weiderpass E, Antoine J, Bray FI, et al.
Trends in corpus uteri cancer mortality in member states of the European Union.
Eur J Cancer. 2014; 50(9):1675-84 [PubMed] Related Publications
OBJECTIVES: The burden of corpus uteri cancer varies in the European Union (EU). We analysed trends in corpus uteri cancer mortality in 26 EU member states from 1970 onward.
METHODS: Population numbers and number of uterine cancer deaths were extracted from the World Health Organisation mortality database. Corpus uteri cancer mortality rates were corrected for certification problems using different reallocation rules for deaths registered as uterine cancer not otherwise specified, or using mixed disease codes. Join point regression was used to study the annual percentage change of age-standardised corpus uteri cancer mortality rates. Changes in corpus uteri cancer mortality rates by calendar period and standardised cohort mortality ratios were also estimated.
RESULTS: In 2008, 12,903 women died from corpus uteri cancer in the EU. Corrected age-standardised corpus uteri cancer mortality rates have decreased significantly over the past decades in most member states, with exception of Malta and Bulgaria, where rates increased; Greece, where rates remained low but stable; and Sweden, where rates have been stable since 1970. Original member states showed a steeper decrease than newer member states. The standardised cohort mortality ratios indicated that corpus uteri cancer mortality does not decrease further, nor does it increase, among women born after 1940, although these birth cohorts may still be too young for corpus uteri cancer incidence to be fully evaluated.
CONCLUSION: Our corrected corpus uteri cancer mortality rates showed a decrease in most EU member states among women born before 1940.
Cancer Registry of Norway, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Genetic Epidemiology, Folkhälsan Research Center, H...

Lindholm ML, Brudin L, Sandin RH
Cumulated time with low bispectral index values is not related to the risk of new cancer or death within 5 years after surgery in patients with previous or prevailing malignancy.
Anesth Analg. 2014; 118(4):782-7 [PubMed] Related Publications
BACKGROUND: Preclinical data indicate that anesthesia and surgery may promote cancer growth. We previously found no increased risk of malignant disease within 5 years regarding duration of general anesthesia (TANESTH) and time with Bispectral Index (BIS) under 45 (TBIS < 45) in patients without any diagnosis or history of malignancy before or within 1 month after surgery. Because immunocompetence may be different in patients with previous malignant disease, we investigated the corresponding risk in patients with earlier or existing malignant disease at the time of surgery.
METHODS: In a prospective cohort of 766 BIS-monitored patients anesthetized with sevoflurane, new malignant diagnoses and death within 5 years after surgery were retrieved. Cox regression was used to assess the risk of new cancer and all-cause death during follow-up in relation to (TANESTH) and (TBIS <45).
RESULT: Fifty-one patients (6.7%) were assigned 54 new malignant diagnoses within 5 years after surgery. Cancer surgery comprised 387 (51%) of the index operations. Two hundred ninety-three (38 %) of the patients died during follow-up. No relation between TANESTH or TBIS <45 and new malignant disease (hazard ratio [HR] 0.64-1.11 and 0.76-1.30, respectively) or death was found (HR 0.85-1.05 and 0.94-1.16, respectively). Nor were any corresponding significant relations obtained when other thresholds for BIS (i.e., < 30, 40, and 50, respectively) were investigated.
CONCLUSION: In patients with previous or existing malignant disease, neither duration of anesthesia nor increased cumulative time with profound sevoflurane anesthesia was associated with an increased risk for new cancer or death within 5 years after surgery. Monitoring "depth of anesthesia" is not expected to alter the risk of cancer proliferation after surgery.

Related: Cancer Prevention and Risk Reduction
From the Departments for *Anesthesia and Intensive Care and †Clinical Physiology, Lanssjukhuset, Kalmar; Department of Medicine and Health Sciences, University Hospital Linköping, Linköping; and ‡Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, St...

Mäkinen N, Heinonen HR, Sjöberg J, et al.
Mutation analysis of components of the Mediator kinase module in MED12 mutation-negative uterine leiomyomas.
Br J Cancer. 2014; 110(9):2246-9 [PubMed] Article available free on PMC after 29/04/2015 Related Publications
BACKGROUND: Kinase module of Mediator complex ('CDK8 submodule') consists of four subunits: CDK8, Cyclin C, MED12, and MED13. Recently, we reported recurrent MED12 mutations in 70% of uterine leiomyomas. The aim of this study was to analyse whether mutations in other components of the module contribute to the development of these lesions.
METHODS: Mutation screening of altogether 70 MED12 mutation-negative uterine leiomyomas was carried out by direct sequencing.
RESULTS: None of the tumours displayed somatic mutations in the coding regions of CDK8/CDK19, CCNC, or MED13.
CONCLUSIONS: Mutations in CDK8/CDK19, CCNC, and MED13 do not frequently contribute to genesis of uterine leiomyomas.
Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, PO Box 63, 00014 Helsinki, Finland.

Chen H, Jiang J, Gao J, et al.
Tumor volumes measured from static and dynamic 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan: comparison of different methods using magnetic resonance imaging as the criterion standard.
J Comput Assist Tomogr. 2014 Mar-Apr; 38(2):209-15 [PubMed] Related Publications
OBJECTIVE: The objective of this study was to compare the accuracy of calculating the primary tumor volumes using a gradient-based method and fixed threshold methods on the standardized uptake value (SUV) maps and the net influx of FDG (Ki) maps from positron emission tomography-computed tomography (PET-CT) images.
MATERIALS AND METHODS: Newly diagnosed patients with head and neck cancer were recruited, and dynamic PET-CT scan and T2-weighted magnetic resonance imaging were performed. The maps of Ki and SUV were calculated from PET-CT images. The tumor volumes were calculated using a gradient-based method and a fixed threshold method at 40% of maximal SUV or maximal Ki. Four kinds of volumes, VOLKi-Gra (from the Ki maps using the gradient-based method), VOLKi-40% (from the Ki maps using the threshold of 40% maximal Ki), VOLSUV-Gra (from the SUV maps using the gradient-based method), and VOLSUV-40% (from the SUV maps using the threshold of 40% maximal SUV), were acquired and compared with VOLMRI (the volumes acquired on T2-weighted images) using the Pearson correlation, paired t test, and similarity analysis.
RESULTS: Eighteen patients were studied, of which 4 had poorly defined tumors (PDT). The positron emission tomography-derived volumes were as follows: VOLSUV-40%, 2.1 to 41.2 cm (mean [SD], 12.3 [10.6]); VOLSUV-Gra, 2.2 to 28.1 cm (mean [SD], 13.2 [8.4]); VOLKi-Gra, 2.4 to 17.0 cm (mean [SD], 9.5 [4.6]); and VOLKi-40%, 2.7 to 20.3 cm (mean [SD], 12.0 [6.0]). The VOLMRI ranged from 2.9 to 18.1 cm (mean [SD], 9.1 [3.9]). The VOLKi-Gra significantly correlated with VOLMRI with the highest correlation coefficient (PDT included, R = 0.673, P = 0.002; PDT excluded, R = 0.841, P < 0.001) and presented no difference from VOLMRI (P = 0.672 or 0.561, respectively, PDT included and excluded). The difference between VOLKi-Gra and VOLMRI was also the smallest.
CONCLUSIONS: The tumor volumes delineated on the Ki maps using the gradient-based method are more accurate than those on the SUV maps and using the fixed threshold methods.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology
From the *Department of Radiology, Guangzhou Panyu Central Hospital; †Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou; ‡Department of Radiology, Peking University Shenzhen Hospital, Shenzhen; §Department of Diagnostic Radiology, The University o...

Davies AR, Sandhu H, Pillai A, et al.
Surgical resection strategy and the influence of radicality on outcomes in oesophageal cancer.
Br J Surg. 2014; 101(5):511-7 [PubMed] Related Publications
BACKGROUND: The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic (TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO.
METHODS: This was a cohort study based on two prospectively created databases. Short- and long-term outcomes for patients undergoing THO and TTO were compared. The primary outcome measure was overall survival, with secondary outcomes including time to recurrence and patterns of disease relapse. A Cox proportional hazards model provided hazard ratios (HRs) and 95 per cent confidence intervals (c.i.), with adjustments for age, tumour stage, tumour grade, response to chemotherapy and lymphovascular invasion.
RESULTS: Of 664 included patients (263 THO, 401 TTO), the distributions of age, sex and histological subtype were similar between the groups. In-hospital mortality (1·1 versus 3·2 per cent for THO and TTO respectively; P = 0·110) and in-hospital stay (14 versus 17 days respectively; P < 0·001) favoured THO. In the adjusted model, there was no difference in overall survival (HR 1·07, 95 per cent c.i. 0·84 to 1·36) or time to tumour recurrence (HR 0·99, 0·76 to 1·29) between the two operations. Local tumour recurrence patterns were similar (22·8 versus 24·4 per cent for THO and TTO respectively). No subgroup could be identified of patients who had benefited from more radical surgery on the basis of tumour location or stage.
CONCLUSION: There was no difference in survival or tumour recurrence for TTO and THO.

Related: Cancer of the Esophagus Esophageal Cancer
Department of Surgery, St Thomas' Hospital, King's College London, London, UK; Department of Surgery, Royal Marsden Hospital, King's College London, London, UK; Gastrointestinal Cancer, Division of Cancer Studies, King's College London, London, UK; Unit of Upper Gastrointestinal Research, Departmen...

Harris HR, Orsini N, Wolk A
Vitamin C and survival among women with breast cancer: a meta-analysis.
Eur J Cancer. 2014; 50(7):1223-31 [PubMed] Related Publications
BACKGROUND: The association between dietary vitamin C intake and breast cancer survival is inconsistent and few studies have specifically examined vitamin C supplement use among women with breast cancer. The purpose of this study was to summarise results from prospective studies on the association between vitamin C supplement use and dietary vitamin C intake and breast cancer-specific mortality and total mortality.
METHODS: Studies were identified using the PubMed database through February 6, 2014 and by examining the references of retrieved articles. Prospective studies were included if they reported relative risks (RR) with 95% confidence intervals (95% CIs) for at least two categories or as a continuous exposure. Random-effects models were used to combine study-specific results.
RESULTS: The ten identified studies examined vitamin C supplement use (n=6) and dietary vitamin C intake (n=7) and included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72-0.91) for total mortality and 0.85 (95% CI 0.74-0.99) for breast cancer-specific mortality. The summary RR for a 100mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59-0.89) for total mortality and 0.78 (95% CI 0.64-0.94) for breast cancer-specific mortality.
CONCLUSION: Results from this meta-analysis suggest that post-diagnosis vitamin C supplement use may be associated with a reduced risk of mortality. Dietary vitamin C intake was also statistically significantly associated with a reduced risk of total mortality and breast cancer-specific mortality.

Related: Breast Cancer
Unit of Nutritional Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA. Electronic address:

Isaksson J, Salander P, Granström B, Laurell G
Critical incidents reveal how patients with head and neck cancer construct their "secure base" as a "helping system".
J Psychosoc Oncol. 2014; 32(3):322-41 [PubMed] Related Publications
Most studies of the psychosocial needs of patients with head and neck cancers (HNC) use predefined categories and explicitly ask for specified needs. These studies are important but should be complemented with inductive studies based on patients' own descriptions of experiences. This qualitative study is such a contribution. In repeated interviews positive and negative incidents were collected from 137 patients with HNC, and these experiences were categorized in dimensions expressing needs. A core category--"being included--neglected by a helping system"--emerged from the narrated incidents and was based on the dimensions engagement, competence, and information. The findings are easily related to attachment theory by stressing the significance of establishing trustful relationships with the health care staff, as attachment figures, who respond flexibly and sensitively to the patient's needs. In the constitution of health care as a helping system, all encounters between the patient and health care staff matters. Further research should preferably focus on the creation of guidelines for the constitution of health care as a helping system, that is, how the found factors of a helping system can be operationalized in clinical practice.

Related: Head and Neck Cancers Head and Neck Cancers - Molecular Biology
a Department of Social Work , Umeå University , Umeå , Sweden.

Ghalali A, Ye ZW, Högberg J, Stenius U
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and PH domain and leucine-rich repeat phosphatase cross-talk (PHLPP) in cancer cells and in transforming growth factor β-activated stem cells.
J Biol Chem. 2014; 289(17):11601-15 [PubMed] Article available free on PMC after 29/04/2015 Related Publications
Akt kinase controls cell survival, proliferation, and invasive growth and is a critical factor for cancer development. Here we describe a cross-talk between phosphatases that may preserve levels of activated/phosphorylated Akt and confer aggressive growth of cancer cells. In prostatic cancer cells, but not in non-transformed cells or in prostate stem cells, we found that the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) overexpression down-regulated PH domain and leucine-rich repeat phosphatase (PHLPP) and that PHLPP overexpression down-regulated PTEN. We also show that silencing PTEN by siRNA increased the levels of PHLPPs. This cross-talk facilitated invasive migration and was mediated by epigenetic alterations, including activation of miR-190, miR-214, polycomb group of proteins, as well as DNA methylation. A role for the purinergic receptor P2X4, previously associated with wound healing, was indicated. We also show that TGF-β1 induced cross-talk concomitant with epithelial-mesenchymal transition in stem cells. The cross-talk emerged as an integrated part of epithelial-mesenchymal transition. We conclude that cross-talk between PTEN and PHLPPs is silenced in normal prostate cells but activated in TGF-β1 transformed prostate stem and cancer cells and facilitates invasive growth.

Related: PTEN Prostate Cancer
From the Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden.

Bill-Axelson A, Holmberg L, Garmo H, et al.
Radical prostatectomy or watchful waiting in early prostate cancer.
N Engl J Med. 2014; 370(10):932-42 [PubMed] Related Publications
BACKGROUND: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.
METHODS: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.
RESULTS: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).
CONCLUSIONS: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).

Related: Prostate Cancer Watchful Waiting - Prostate Cancer
From the Departments of Surgical Sciences (A.B.-A., M.H.) and Immunology, Genetics, and Pathology (C.B.), and the Regional Cancer Center Uppsala Örebro (L.H., H.G.), Uppsala University Hospital, Uppsala, the School of Health and Medical Sciences, Örebro University and Department of Urolog...
Research funded by:

Joneborg U, Marions L
Current clinical features of complete and partial hydatidiform mole in Sweden.
J Reprod Med. 2014 Jan-Feb; 59(1-2):51-5 [PubMed] Related Publications
OBJECTIVE: To describe the current clinical presentation of complete (CHM) and partial (PHM) hydatidiform mole in a Swedish setting.
STUDY DESIGN: A retrospective analysis of medical charts from 331 women with hydatidiform mole (HM) between 1991 and 2010 was performed. Demographics and clinical features were analyzed, and symptoms in women with CHM were compared to those from a historic group (1988 to 1993) from the New England Trophoblastic Disease Center.
RESULTS: In women with CHM, bleeding was more common than in women with PHM (57% vs. 41%, p < 0.001) but significantly less common as compared to the historic group (84%). Women with CHM and PHM were diagnosed before the onset of symptoms in 32% and 53%, respectively, compared to the previously reported 10% (p < 0.001). There was a significantly higher proportion of women 240 years of age with CHM than with PHM (23% vs. 7%). Ultrasound predicted the molar diagnosis in 73% of CHMs and 35% of PHMs (p < 0.001).
CONCLUSION: In our study a large proportion of molar pregnancies were asymptomatic at the time of diagnosis. This confirms earlier reports of the changing clinical presentation of HM and shows that this trend continues. Age, ultrasound findings and hCG levels can add valuable information.
Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.

Sclafani F, Gonzalez D, Cunningham D, et al.
RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial.
Eur J Cancer. 2014; 50(8):1430-6 [PubMed] Related Publications
BACKGROUND: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial.
METHODS: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed.
RESULTS: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n=40; CAPOX-C, n=38). In this population, after a median follow-up of 63.8months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p=0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p=0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p=0.20).
CONCLUSIONS: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted.

Related: Fluorouracil Oxaliplatin Capecitabine Cetuximab (Erbitux)
The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.

Stålberg K, Svensson T, Lönn S, Kieler H
The influence of comorbidity on mortality in ovarian cancer patients.
Gynecol Oncol. 2014; 133(2):298-303 [PubMed] Related Publications
BACKGROUND: Ovarian cancer is a severe disease with a peak incidence in the older age groups where concurrent morbidity is common and could potentially influence mortality rates.
OBJECTIVES: The aim was to study the influence of common comorbidity diagnoses on mortality in ovarian cancer patients.
METHODS: The study population was patients with ovarian cancer in Sweden 1993-2006 (n=11.139) identified in the national Cancer Register. Comorbidity data was obtained from the Patient Register and mortality from Cause of Death Register. Mortality was analyzed with Cox' proportional hazards models and subgroup analyses were performed by age and tumor histology.
RESULTS: Almost all of the assessed comorbidities increased mortality in ovarian cancer patients. Thromboembolism was the most hazardous comorbidity (HR=1.95, <1 year after cancer diagnosis and HR=7.83, 1-5 years after cancer diagnosis) followed by hematologic complications (HR=1.84 and 7.11 respectively) and infectious disease (HR=1.48 and 5.28 respectively). The occurrence of diabetes mellitus and hypertension had less impact on mortality.
CONCLUSION: Thromboembolism, hematologic complications and infections had a pronounced effect on mortality rates in women with ovarian cancer. The impact of comorbidity was mainly apparent among those with a more prosperous prognosis, such as longer time since cancer diagnosis, less aggressive tumors and younger age.

Related: Germ Cell Tumors Ovarian Cancer Soft Tissue Sarcomas
Department of Women's and Children's Health, Uppsala University, 75185 Uppsala, Sweden. Electronic address:

Al-Haidari AA, Syk I, Thorlacius H
HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation.
Biochem Biophys Res Commun. 2014; 446(1):68-72 [PubMed] Related Publications
BACKGROUND: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects.
AIM: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration.
METHODS: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay.
RESULTS: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells.
CONCLUSIONS: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via inhibition of geranylgeranylation and RhoA activation. Thus, statins, such as simvastatin, might be effective tools to antagonize CCL17-dependent migration and metastasis of colon cancer cells.

Related: Apoptosis RHOA
Department of Clinical Sciences, Section of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.

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