Literature on familial risk of carcinomas in situ (CISs) is limited because many cancer registries do not collect information on CIS. In Sweden CISs are collected, and we used these data to analyze familial relative risks (RRs) for concordant (CIS-CIS) types of anogenital (cervical, other female and male genital and anal) and skin squamous cell CIS; additionally RRs were assessed between CIS types and between CIS and invasive forms. RRs were calculated for the offspring generations when family members were diagnosed CIS. Case numbers for CIS ranged from 330 in anal to 177,285 in cervical CIS. Significant concordant CIS-CIS RRs were 2.74 for female genital, 1.77 for cervical and 2.29 for SCC skin CISs. The CIS forms associated also with each other, except for cervical and skin CIS types. RRs for concordant CIS-invasive cancer associations were lower than CIS-CIS associations. Cervical CIS associated with non-Hodgkin CIS which may suggest immune dysfunction as a contributing factors. The results for anogenital CIS types suggest that life style related human papilloma virus infections contributed to the observed familial associations. Lower risks for CIS-invasive cancer than CIS-CIS suggest that CIS and invasive cancers share only partially risk factors that underlie familial clustering.

Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.

Introduction Hurthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. Methods We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. Results Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. Conclusion This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

There are many known endocrine complications after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood including increased risk of biochemical hypogonadism. However, little is known about sexuality in adulthood following childhood HSCT. In this multicenter study, sexual functions and possible risk factors were assessed comprehensively in two national cohorts (Finland and Denmark) of male adult survivors of childhood HSCT. Compared to a healthy control group (n= 56), HSCT survivors (n= 97) reported less sexual fantasies, poorer orgasms, lower sexual activity with a partner and reduced satisfaction with their sex life, even in the presence of normal erectile functions and a similar frequency of autoerotic acts. Of the HSCT survivors, 35% were cohabitating/married and 66% were sexually active. Risk factors for poorer self-reported sexual functions were partner status (not cohabitating with a partner), depressive symptoms, CNS and testicular irradiation. Sexual dysfunction increased by age in the HSCT group with a pace comparable to that of the control group. However, because of the lower baseline level of sexual functions in the HSCT group, they will reach the level of clinically significant dysfunction at a younger age. Hence, male survivors of childhood HSCT should be interviewed in detail about their sexual health beyond erectile functions.

Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi-directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (2458 for insitu and 763 for invasive), Merkel cell carcinoma (1436), Hodgkin lymphoma (716) and Kaposi sarcoma (676). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 1535 after myeloid neoplasia. HCL showed reciprocally increased RRs with non-Hodgkin lymphoma and melanoma. The concordance between RRs for bi-directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi-directional risks with skin cancers and other immune-related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.

Background Distinguishing intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic lesions is essential since IPMNs carry the risk of becoming malignant. Differentiating the main pancreatic duct involving IPMNs (MD-IPMNs) through conventional imaging is deficient. Single-operator peroral pancreatoscopy (SOPP) represents a promising method offering additional information on suspected lesions in the pancreatic main duct (MD). We aimed to determine the role of SOPP in the preoperative diagnostics of suspected MD-IPMNs and identify factors contributing to SOPP-related complications. Materials and Methods In this primarily retrospective study, SOPPs were performed at three high-volume centers on suspected MD-IPMNs. Primary outcome was the clinical impact of SOPP to subsequent patient care. Additionally, we documented post-SOPP complications and analyzed several assumed patient- and procedure-related risk factors. Results One hundred and one (101) SOPPs were performed. Subsequent clinical management was affected due to the findings in 86 (85%) cases. Surgery was planned for 29 (29%) patients. A condition other than IPMN explaining MD dilatation was found in 28 (28%) cases. In 35 (35%) cases, follow-up with MRI was continued. Post-SOPP pancreatitis occurred in 20 (20%) patients and one of them was fatal. A decrease in odds of post-SOPP pancreatitis was seen as the MD diameter increases (OR 0.714 for 1.0 mm increase in MD diameter, CI 95% 0.514-0.993, p = 0.045). Furthermore, a correlation between lower MD diameter values and higher severity post-SOPP pancreatitis was seen (T-JT = 599, SE = 116.6, z = - 2.31; p = 0.020). History of pancreatitis after endoscopic retrograde cholangiopancreatography was a confirmed risk factor for post-SOPP pancreatitis. Conclusions between complications and other risk factors could not be drawn. Conclusion SOPP aids clinical decision-making in suspected MD-IPMNs. Risk for post-SOPP pancreatitis is not negligible compared to non-invasive imaging methods. The risk for pancreatitis decreases as the diameter of the MD increases.

Objective: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to bile duct strictures and fibrosis, and predisposing to cholangiocarcinoma (CCA). Biliary dysplasia is a known precursor of CCA. In our unit, PSC patients undergo regular surveillance with ERC and brush cytology (BC), and liver transplantation is an option in case with biliary dysplasia. We evaluated the risk factors for biliary dysplasia and CCA based on ERC imaging, BC and liver function tests. Patients and methods: Seven hundred and eighty-eight ERCs were performed with BC for 447 PSC patients. ERC images were evaluated using the modified Amsterdam score, neutrophilic inflammation was assessed in BC, and liver function tests were collected. Ploidy analysis with DNA flow cytometry was performed in cases with advanced PSC or previous suspicious BC/aneuploidy. The endpoint was either a benign disease course (follow-up for >= 2.4 years after the latest ERC), benign histology, biliary dysplasia or CCA. Results: Benign disease course was seen in 424/447 (including 23 cases with biliary dysplasia), and CCA in 17 (3.8%) patients. Gallbladder carcinoma/carcinoma in situ was diagnosed in three patients. Advanced ERC findings, male gender, suspicious BC, aneuploidy in flow cytometry, inflammation, and elevation of ALP, bilirubin, ALT, AST, GGT, CEA and CA19-9 represented significant risk factors for CCA in univariate analysis. Conclusions: PSC patients with advanced bile duct disease and elevated liver enzymes, CEA or CA19-9, inflammation or suspicious BC are most likely to develop CCA. These patients may benefit from surveillance with BC if early liver transplantation is possible.

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.

Introduction and aim: Venous thromboembolism (VTE) is a severe complication associated both with major orthopaedic surgery and cancer. However, survival and postoperative complications of skeletal metastases despite their thrombogenic potential, have received little attention in both the clinical management and research setting. This single-centre observational cohort study aimed to evaluate the incidence and impact of VTE in association with cancer surgery targeted to the management of fractures secondary to skeletal metastases. Methods: Data were collected retrospectively from the medical database. We included consecutive 306 patients operated for 343 non-spinal skeletal metastases during a 15-year period (1999-2014). The incidence of VTE and its risk factors were assessed using binary logistic regression analysis. Kaplan-Meier and Cox regression analyses were used to evaluate variables affecting survival. Results: The rate of symptomatic VTE was 10% (30/306) during the 3-month postoperative period, while 79% received thromboprophylaxis. Fatal pulmonary embolism (PE) rate was high, 3.3% (10/306) after surgery. Intraoperative oxygen saturation drop, pulmonary metastases and intramedullary nailing were independent risk factors for VTE. Indicators of decreased survival were lung cancer, intramedullary nailing, multiple skeletal and pulmonary metastases, anaemia, leukocytosis, and PE. Conclusion: Relationship between fractures secondary to skeletal metastases and VTE needs further clinical attention. Whether the survival of patients with fractures secondary to skeletal metastases can be improved by targeted thromboprophylactic means should be studied further. (C) 2016 Elsevier Ltd. All rights reserved.