Citations

Abstract A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P < 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.

Clonal eosinophilic disorders are rare among hematological malignancies. Most eosinophilia tends to be due to secondary causes such as infections, hypersensitivity conditions, drug reactions, and connective tissue disorders. The presence of a primary clonal eosinophilic disorder such as chronic eosinophilic leukemia—not otherwise specified (NOS) in the presence of a synchronous large cell lymphoma—is rare making the diagnosis challenging. We present a case of a 51-year-old female with the aforementioned presentation and demonstrate the extensive workup performed to identify the diagnosis.

Central nervous system metastases as the presentation of primary cardiac sarcoma are a very rare entity, with only a few previously reported cases. Sarcomas specifically make up 10 to 20% of all primary cardiac tumors. Patients with primary cardiac tumors typically present with cardiac symptomatology that may include arrhythmias, obstruction to blood flow and valve function, or symptoms of heart failure. We report a unique case of a patient with a primary cardiac sarcoma who presented with progressive neurologic dysfunction secondary to brain metastases without any preceding cardiac symptoms. We describe our novel management of these unique cases and discuss the current medical and surgical approaches to treating neurologic metastases from cardiac sarcoma.

Shapiro syndrome and periodic hypothermia have been reported approximately fifty times in the literature. Shapiro syndrome is defined as the constellation of periodic hypothermia and hyperhidrosis along with agenesis of the corpus callosum by Shapiro et al. in 1969. Periodic hypothermia is a more broad diagnosis with a number of proposed mechanisms; it occurs in patients without structural brain abnormalities. Hematologic abnormalities beyond iron-deficiency anemia have not been documented in any of the reported cases of Shapiro syndrome or periodic hypothermia. Though accidental and therapeutic hypothermia have been associated with thrombocytopenia, this is, to our knowledge, the first reported case of periodic intrinsic hypothermia causing bicytopenia. In this report, we present the case of a patient with Shapiro syndrome who experienced cyclic bicytopenia mirroring hypothermic episodes. We address the differential diagnosis of bicytopenia, review the mechanisms proposed for cytopenias related to hypothermia, and propose possible mechanisms for the finding in this case.

The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.

Background The heart and lungs are intimately linked anatomically and physiologically, and, as a result, heart failure (HF) patients often develop changes in pulmonary function. This study examined the prognostic value of resting pulmonary function (PF) in HF. Methods and Results In all, 134 HF patients (enrolled from January 1, 1999 Through December 31, 2005; ejection fraction (EF) = 29% ± 11%; mean age = 55 ± 12 years; 65% male) were followed for 67 ± 34 months with death/transplant confirmed via the Social Security Index and Mayo Clinic registry. PF included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), diffusing capacity of the lungs for carbon monoxide (DL CO ), and alveolar volume (VA). Patients were divided in tertiles according to PF with survival analysis via log-rank Mantel-Cox test with chi-square analysis. Groups for FVC included (1) >96%, (2) 96% to 81%, and (3) <81% predicted (chi-square = 18.9, P< 0.001). Bonferroni correction for multiple comparisons (BC) suggested differences between groups 1 and 3 (P < 0.001) and 2 and 3 ( P = 0.008). Groups for FEV 1 included (1) >94%, (2) 94% to 77%, and (3) <77% predicted (chi-square = 17.3, P < 0.001). BC suggested differences between groups 1 and 3 ( P < 0.001). Groups for DL CO included (1) >90%, (2) 90% to 75%, and (3) <75% predicted (chi-square = 11.9, P = 0.003). BC suggested differences between groups 1 and 3 >( P < 0.001). Groups for VA included (1) <97%, (2) 97% to 87%, and (3) <87% predicted (Chi-square = 8.5, P = 0.01). BC suggested differences between groups 1 and 2 ( P = 0.014) and 1 and 3 >( P = 0.003). Conclusions In a well-defined cohort of HF patients, resting measures of PF are predictive of all-cause mortality.

Key Points A continued monoclonal protein response after ASCT in the absence of further therapy is prognostic in MM patients.