Hereditary Settings Research Articles

Treatment of Microsatellite-Unstable Rectal Cancer in Sporadic and Hereditary Settings.

Microsatellite instability is rare in rectal cancer and associated with younger age of onset and Lynch syndrome. All rectal cancers should be tested for microsatellite instability prior to treatment decisions. Patients with microsatellite instability are relatively resistant to chemotherapy. However, recent small studies have shown dramatic response with neoadjuvant immunotherapy. Patients with Lynch syndrome have a hereditary predisposition to cancer and thus an elevated risk of metachronous cancer. Therefore, while "watch and wait" is a well-established practice for sporadic rectal cancers that obtain a complete clinical response after chemoradiation, its safety in patients with Lynch syndrome has not yet been defined. The extent of surgery for patients with Lynch syndrome and rectal cancer is controversial and there is significant debate as to the relative advantages of a segmental proctectomy with postoperative endoscopic surveillance versus a therapeutic and prophylactic total proctocolectomy. Surgical decision making for the patient with Lynch syndrome and rectal cancer is complex and demands a multidisciplinary approach, taking into account both patient- and tumor-specific factors. Neoadjuvant immunotherapy show great promise in the treatment of these patients, and further maturation of data from prospective trials will likely change the current treatment paradigm. Patients with Lynch syndrome and rectal cancer who do not undergo total proctocolectomy require yearly surveillance colonoscopies and should consider chemoprophylaxis with aspirin.

τ-exceptional sequences

We introduce the notions of τ-exceptional and signed τ-exceptional sequences for any finite dimensional algebra. We prove that for a fixed algebra of rank n, and for any positive integer t≤n, there is a bijection between the set of signed τ-exceptional sequences of length t, and (basic) ordered support τ-rigid objects with t indecomposable direct summands. If the algebra is hereditary, our notions coincide with exceptional and signed exceptional sequences. The latter were recently introduced by Igusa and Todorov, who constructed a similar bijection in the hereditary setting.

Discovering the Mutational Profile of Early Colorectal Lesions: A Translational Impact.

Simple SummaryColorectal cancer (CRC) is one of the most common malignancies worldwide. Next-generation sequencing technologies have identified new candidate genes and deepened the knowledge of the molecular mechanisms underlying the progression of colonic adenomas towards CRC. The main genetic, epigenetic, and molecular alterations driving the onset and progression of CRC in both hereditary and sporadic settings have also been investigated. The evaluation of the CRC risk based on the molecular characterization of early pre-cancerous lesions may contribute to the development of targeted preventive strategies development, help define specific risk profiles, and identify patients who will benefit from targeted endoscopic surveillance.Colorectal cancer (CRC) develops through a multi-step process characterized by the acquisition of multiple somatic mutations in oncogenes and tumor-suppressor genes, epigenetic alterations and genomic instability. These events lead to the progression from precancerous lesions to advanced carcinomas. This process requires several years in a sporadic setting, while occurring at an early age and or faster in patients affected by hereditary CRC-predisposing syndromes. Since advanced CRC is largely untreatable or unresponsive to standard or targeted therapies, the endoscopic treatment of colonic lesions remains the most efficient CRC-preventive strategy. In this review, we discuss recent studies that have assessed the genetic alterations in early colorectal lesions in both hereditary and sporadic settings. Establishing the genetic profile of early colorectal lesions is a critical goal in the development of risk-based preventive strategies.

The Fair Division of Hereditary Set Systems

We consider the fair division of indivisible items using the maximin shares measure. Recent work on the topic has focused on extending results beyond the class of additive valuation functions. In this spirit, we study the case where the items form a hereditary set system. We present a simple algorithm that allocates each agent a bundle of items whose value is at least 0.3666 times the maximin share of the agent. This improves upon the current best known guarantee of 0.2 due to Ghodsi et al. The analysis of the algorithm is almost tight; we present an instance where the algorithm provides a guarantee of at most 0.3738. We also show that the algorithm can be implemented in polynomial time given a valuation oracle for each agent.

Les cancers du rein héréditaires vus par le pathologiste en 2020

Hereditary predispositions to adult kidney tumors involve around 5% of tumors and include a dozen of autosomal dominant syndromes. The most frequent tumors encountered in these setting are clear cell renal cell carcinomas, papillary renal cell carcinomas, chromophobe renal cell carcinomas and angiomyolipomas. Their detection is essential in order to adapt individual care and perform genetic screening of at-risk relatives, especially in the national french network PREDIR, labeled by the National Cancer Institute and dedicated to hereditary predispositions to kidney tumors. Targeted genetic analysis, which was guided in particular by the renal tumor subtype, has recently evolved into genetic analysis using panels of genes. Pathologist contribution's remains however central in the diagnosis of hereditary forms since we currently have immunohistochemical biomarkers that allow us to diagnose two specifically hereditary entities: hereditary leiomyomatosis and renal cell carcinoma associated-renal cell carcinoma, associated with a loss of fumarate hydratase and succinate dehydrogenase-deficient renal cell carcinoma associated with a loss of succinate deshydrogenase B expression. These diagnoses must however be confirmed by the identification of pathogenic germline variation in the corresponding genes. Improvement of kidney tumors characterization has also lead to identify new subtypes, expanding the algorithm of renal tumors associated with hereditary setting. Here we aim to review all subtypes of adult renal tumors encountered in predisposition syndromes.

Un léiomyome utérin particulier

Fumarate hydratase (FH)-deficient uterine leiomyomas represent 1% of all uterine leiomyomas. They show distinctive morphology, and are often associated with a loss of expression of FH protein, secondary to the inactivation of the FH gene. They can occur sporadically or in the hereditary setting of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome associated with germline mutations of FH gene. So, it is relevant to consider this diagnosis in case of young women with numerous or bulky leiomyomas and evocative microscopic features, in particular at nuclear level. Genetic screening is essential to identify hereditary forms, which require appropriate surveillance and genetic screening of relatives. Here, we report the case of a 20cm uterine leiomyoma in a young 32-year-old woman, whose morphologic and immunohistochemical characteristics were suggestive of FH-deficient leiomyoma.

Moment Problems in Hereditary Function Spaces

Abstract We introduce a concept of hereditary set of multi-indices, and consider vector spaces of functions generated by families associated to such sets of multi-indices, called hereditary function spaces. Existence and uniquenes of representing measures for some abstract truncated moment problems are investigated in this framework, by adapting the concept of idempotent and that of dimensional stability, and using some techniques involving C*-algebras and commuting self-adjoint multiplication operators.

Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity.

Approximately 5-10% of cutaneous melanoma occurs in kindreds with a hereditary predisposition. Mutations in the CDKN2A gene are found to occur in approximately 20-40% of these kindreds. The first historical mention of what is now called the familial atypical multiple mole melanoma syndrome appears to be from 1820, with more reports throughout the 1950s, 1960s, and later years. In 1991, Lynch and Fusaro described an association between familial multiple mole melanoma and pancreatic cancer and work continues to elucidate the syndrome's genotypic and phenotypic heterogeneity. Individuals at risk for familial melanoma need periodic screenings. Unfortunately, adequate screening for pancreatic cancer does not currently exist, but pancreatic cancer's prominence in the hereditary setting will hopefully act as a stimulus for development of novel screening measures.

Extreme cycles. The center of a Leavitt path algebra

In this paper we introduce new techniques in order to deepen into the structure of a Leavitt path algebra with the aim of giving a description of the center. Extreme cycles appear for the first time; they concentrate the purely infinite part of a Leavitt path algebra and, jointly with the line points and vertices in cycles without exits, are the key ingredients in order to determine the center of a Leavitt path algebra. Our work will rely on our previous approach to the center of a prime Leavitt path algebra \cite{CMMSS1}. We will go further into the structure itself of the Leavitt path algebra. For example, the ideal $I(P_{ec} \cup P_{c} \cup P_l)$ generated by vertices in extreme cycles ($P_{ec}$), by vertices in cycles without exits ($P_c$) and by line points ($P_l$) will be a dense ideal in some cases, for instance in the finite one or, more generally, if every vertex connects to $P_l \cup P_c\cup P_{ec}$. Hence its structure will contain much of the information about the Leavitt path algebra. In the row-finite case, we will need to add a new hereditary set: the set of vertices whose tree has infinite bifurcations ($P_{b^\infty}$).

Generic Fibrational Induction

This paper provides an induction rule that can be used to prove properties of data structures whose types are inductive, i.e., are carriers of initial algebras of functors. Our results are semantic in nature and are inspired by Hermida and Jacobs' elegant algebraic formulation of induction for polynomial data types. Our contribution is to derive, under slightly different assumptions, a sound induction rule that is generic over all inductive types, polynomial or not. Our induction rule is generic over the kinds of properties to be proved as well: like Hermida and Jacobs, we work in a general fibrational setting and so can accommodate very general notions of properties on inductive types rather than just those of a particular syntactic form. We establish the soundness of our generic induction rule by reducing induction to iteration. We then show how our generic induction rule can be instantiated to give induction rules for the data types of rose trees, finite hereditary sets, and hyperfunctions. The first of these lies outside the scope of Hermida and Jacobs' work because it is not polynomial, and as far as we are aware, no induction rules have been known to exist for the second and third in a general fibrational framework. Our instantiation for hyperfunctions underscores the value of working in the general fibrational setting since this data type cannot be interpreted as a set.

Association of hyperplastic polyposis syndrome, colorectal cancer and meningioma

Recent research has provided compelling evidence that a subset of hyperplastic polyps may be associated with a risk of colorectal cancer. Colorectal cancer with extracolonic manifestation is usually seen in a hereditary syndrome setting, but some association with meningioma has been reported. The association of colorectal cancer with hyperplastic polyposis and meningioma is extremely rare. This report in a 57-year-old female with no family history of colon cancer or polyps, could be the first case of hyperplastic polyposis syndrome, colorectal cancer and meningioma. Hyperplastic polyposis syndrome was diagnosed as per WHO criteria at the time of colon cancer diagnosis. Within 4 months of colon cancer diagnosis she developed seizures. Imaging of the brain revealed meningioma of the left cerebellopontine angle. The patient underwent surgery followed by chemotherapy.

Delaunay triangulations in O (sort( n )) time and more

We present several results about Delaunay triangulations (DTs) and convex hulls in transdichotomous and hereditary settings: (i) the DT of a planar point set can be computed in expected time O (sort( n )) on a word RAM, where sort( n ) is the time to sort n numbers. We assume that the word RAM supports the shuffle operation in constant time; (ii) if we know the ordering of a planar point set in x - and in y -direction, its DT can be found by a randomized algebraic computation tree of expected linear depth; (iii) given a universe U of points in the plane, we construct a data structure D for Delaunay queries : for any P ⊆ U , D can find the DT of P in expected time O (| P | log log | U |); (iv) given a universe U of points in 3-space in general convex position, there is a data structure D for convex hull queries : for any P ⊆ U , D can find the convex hull of P in expected time O (| P | (log log | U |) 2 ); (v) given a convex polytope in 3-space with n vertices which are colored with χ ≥ 2 colors, we can split it into the convex hulls of the individual color classes in expected time O ( n (log log n ) 2 ). The results (i)--(iii) generalize to higher dimensions, where the expected running time now also depends on the complexity of the resulting DT. We need a wide range of techniques. Most prominently, we describe a reduction from DTs to nearest-neighbor graphs that relies on a new variant of randomized incremental constructions using dependent sampling.

Risk assessment and risk reduction strategies: overview.

Abstract Abstract #MS1-1 In this mini-symposium, we will address the major risk factors for breast cancer, current risk prediction tools, and measures to reduce risk in those women deemed at high risk. Those factors that convey a significantly increased risk of breast cancer (e.g. relative risk greater than 4.0) include: strong family history of breast cancer (i.e. early onset of disease, multiple relatives with disease, including BRCA1/2 carriers); atypical hyperplasia on benign biopsy; older age; and dense breast tissue. Multiple other features are recognized as contributing to breast cancer risk but to a lesser degree. These include having a family history of breast cancer but not with a hereditary pattern (RR approximately 2.0), benign breast disease (RR 1.5), multiple reproductive factors including early menarche, late menopause, current or recent estrogen plus progesterone use, current OC use (all with relative risks in the 1.2-1.3 range); and alcohol use (e.g. 3 drinks per day) (RR∼1.3). Numerous other features such as induced abortion and sedentary lifestyle have been reported to increase risk of breast cancer but to a very minor degree and results are not consistent.
 Several risk prediction models for breast cancer focus on an individual's likelihood of carrying a hereditary predisposition to the disease (e.g. Frank, Couch, Shattuck-Eidens, Parmigiani, BRCAPRO, BOADICEA, Claus). Outside of the hereditary setting, the most widely used tool is the Gail model. Features incorporated in the Gail model include age, family history, number of breast biopsies, age at menarche, age at first live birth, and the presence of atypia on a benign biopsy. While the Gail model has been shown to be calibrated in predicting number of breast cancers likely to develop in groups of women, its discriminatory accuracy in predicting risk for individual women is limited. This limitation is not well appreciated by many clinicians.
 Regarding options for surgical risk reduction in high risk individuals, several studies examined the efficacy of both bilateral and contralateral mastectomy in women at increased risk for breast cancer, including BRCA1/2 carriers. Results consistently show a greater than 90% reduction in risk of subsequent breast cancer. A study by the Cancer Research Network (6 HMOs) examined the impact of contralateral PM on mortality from breast cancer and showed reduced death from breast cancer with CPM (HR 0.57 [0.45-0.72]).
 Studies of risk-reducing salpingo-oophorectomy (RRSO) in BRCA carriers have shown dramatic reductions in risk of subsequent ovarian/peritoneal cancer, providing approximately 90% protection. The reduction in breast cancer risk after RRSO is seen only when the oophorectomy is performed in premenopausal women. Recent data on 368 BRCA1 and 229 BRCA2 carriers from a multicenter study show a differential effect on breast cancer risk following RRSO by mutation type. The hazard ratio for risk of breast cancer in BRCA2 carriers was 0.28 (0.08-0.92) (p 0.04) but for BRCA1 carriers was 0.61 (0.30-1.22) (p 0.16). This appeared to be due to the preponderance of ER-negative breast cancers in BRCA1 carriers, where no risk reduction with RRSO was seen. (N Kauff et al, JCO, 3/10/08) Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr MS1-1.

When an Atomic and Complete Algebra of Sets is a Field of Sets with Nowhere Dense Boundary

We consider pairs 〈 A, H ( A )〉 where A is an algebra of sets from some class called the class of algebras of type 〈 κ , λ 〉 and where H ( A ) is the ideal of hereditary sets of A . We characterize which of the above pairs are topological, that is, which are fields of sets with nowhere dense boundary for some topology together with the ideal of nowhere dense sets for this topology. Making use of a theorem of Fichtenholz and Kantorovich which says that in P ( κ ) there is an independent family of cardinality 2 κ , we construct an example of a pair 〈algebra, ideal〉 with complete quotient algebra and the hull property but not topological. This countrexample, given in ZFC, provides the complete solution of a problem posed in [Balcerzak, Bartoszewicz, Ciesielski, Real Anal. Exchange 29: 265–273, 2003/04]. Such an algebra was constructed in [Bartoszewicz, Topology Appl. 149: 9–15, 2005] under some aditional set theoretic assumption.

Increased Risk of Lymph Node Metastasis in Multifocal Hereditary and Sporadic Medullary Thyroid Cancer

In sporadic and hereditary medullary thyroid cancer, tumor multifocality may constitute an independent risk factor of lymph node metastasis on top of primary tumor size when the diameter of the largest primary tumor is the same. Included in this institutional cohort study were 232 consecutive patients operated on at our institution for hitherto untreated medullary thyroid cancer. Associations of clinicopathologic variables with lymph node metastasis were investigated simultaneously using multivariate Cox regression analysis. On univariate analysis, multifocal cancers developed lymph node metastases significantly more often (p < or = 0.005) than unifocal cancers, in both the sporadic (90% vs. 41%) and the hereditary setting (48% vs. 14%). On multivariate Cox regression analysis on lymph node metastasis as a function of primary tumor diameter, only multifocal (vs. unifocal) tumor growth was significantly associated with lymph node metastasis (odds ratio [OR] = 2.5; p = 0.01). When multifocal growth was removed as an independent variable from the Cox model, heredity became the only significant predictor (OR = 3.1; p < 0.0001). The excess risk of lymph node metastasis of 34%-49% in multifocal medullary thyroid cancer seems to be caused by concurrent smaller thyroid cancers. A diagnosis of more than one medullary thyroid cancer signifies a higher risk of lymph node metastasis, warranting systematic lymph node dissection.

GANDY'S PRINCIPLES FOR MECHANISMS AND MEMBRANE COMPUTING

The interconnections between membrane computing [9,11] and Gandy's principles for mechanisms in [3] are discussed. The embedding of the classes of hereditary finite sets (used to formulate Gandy's principles) into the class of abstract membrane systems is shown. A concept of a hereditary finite multiset is introduced as a special case of hereditary finite sets and then a representation of finite abstract membrane systems by hereditary finite multisets is presented. In this framework, a counterpart of the idea of reassemblance of hereditary finite sets is obtained for membrane systems.

Numbers, Reference and Russellian Propositions

Stewart Shapiro and John Myhill tried to reproduce some features of the intuitionistic mathematics within certain formal intensional theories of classical mathematics. Basically they introduced a knowledge operator and restricted the ways of referring to numbers and to finite hereditary sets. The restrictions are very interesting, both because they allow us to keep substitutivity of identicals notwithstanding the presence of an epistemic operator and, especially, because such restrictions allow us to see, by contrast, which ways of reference are not compatible with the simultaneous maintenance of substitutivity of identicals and the classical notions of truth and knowledge. In this paper the difference between the restricted and the unrestricted kind of reference is put in relation with Russell's ideas on naming and it is argued that the latter as well is compatible with a certain Russellian conception of the understanding of sentences. Then it is discussed whether and how numbers could be conceived as objects of acquaintance. Finally a general question about the notion of logical form is raised.

Microsatellite Instability in Gastrointestinal Tract Cancers: A Brief Update

Microsatellite instability (MSI) was initially reported in colorectal cancer and, particularly, in hereditary nonpolyposis colorectal cancer (HNPCC). Since mutations in the genes functioning in DNA mismatch repair (MMR) were found in HNPCC kindred, this phenotype has been connected to a deficiency in MMR. The MSI(+) phenotype is associated with various human malignancies. As MSI(+) tumors appear to form a unique clinicopathological and molecular entity that is clearly distinct from that of classical colorectal tumors, which are accompanied by chromosomal instability (CIN), an exclusive pathway of tumorigenesis has been proposed in colorectal cancer. However, this scheme, comprising two mutually exclusive pathways, is now being reexamined, in light of a series of evidence accumulating in the literature, which relates to (a) distinction between high-level MSI (MSI-H) and low-level MSI (MSI-L), (b) heterogeneity in MSI-H, particularly in the sporadic and hereditary settings, (c) molecular mechanisms underlying the MSI(+) phenotypes, and (d) relationships between the MSI(+) and CIN phenotypes. Several molecular mechanisms may underlie repeat instability in eukaryotic cells. The relationship between MSI and defective MMR may be more complicated than has been suspected. The role of MMR deficiency in tumorigenesis in the digestive tract appears to be diverse and is not simple, even in the colorectum.

Lynch Syndrome (HNPCC) and Microsatellite Instability

A departure from the concept of simple adenoma to carcinoma sequence is the realization that colorectal cancer (CRC) develops through at least two major molecular pathogenic pathways, namely chromosomal instability (CIN) and microsatellite instability (MSI) [1,2]. The mechanisms underlying CIN might have been the first to be deciphered but they are just being understood in detail. It is proposed that CIN may be associated with defects in mitotic spindle apparatus hence tumors arising through this pathway are usually characterized by widespread chromosomal deletions, translocations and loss of heterozygosity at the molecular level. On the other hand, MSI pathway is responsible for up to 15% of all CRCs that also include a number of familial syndromes [3,4]. Hereditary non-polyposis colorectal cancer (HNPCC also known as Lynch syndrome) is the prototype for the tumors characterized by MSI. Tumors developing through this pathway have alterations in the length of short, repeated (usully mononucleotide or dinucleotide) sequences of DNA, i.e., microsatellites [5–10]. This phenomenon reflects the underlying defect in the DNA mismatch repair (MMR) system which is a multi-protein complex responsible for correction of errors arising during normal cell division [5,7,11,12]. In 1997, the National Cancer Institute Workshop on Hereditary Non-polyposis Colorectal Cancer Syndrome proposed specific markers for MSI assessment which included BAT25, BAT26, D5S346, D2S123 and D17S250, known as Bethesda panel [13]. If no alterations are found the tumor is classified as microsatellite stable (MSS) and if two or more loci are abnormal the tumor is classified as showing a high level of microsatellite instability (MSI-H). In cases showing abnormalities at one locus, testing of an additional five loci is recommended. If abnormal loci constitute less than 40% of the tested markers, the tumor is classified as showing a low level of microsatellite instability (MSIL). MSS cancers account for up to 85% of all CRCs and occur in sporadic and hereditary settings such as familial adenomatous polyposis (FAP) and attenuated FAP. The biological significance and underlying genetic abnormalities in cancers with the MSI-L phenotype are debated and remain to be fully characterised. It has been reported that on morphological grounds, MSS and MSI-L cancers are indistinguishable. MSI-H cancers constitute up to 15% of all CRCs. MSI-H cancers (sporadic and in hereditary non-polyposis colorectal cancer (HNPCC) patients) have characteristic anatomical and histological features. Proximal colon incidence is seen in the majority of cases. Most of the tumors are polypoid masses and some may display a mucinous cut surface [14,15]. Stricture formation due to a diffuse growth pattern is uncommon; however, extensive necrosis is often observed. The tumors usually have a well-defined margin. A significant fraction of tumors are also classified as poorly differentiated. A characteristic feature of diagnostic importance is the presence of tumor infiltrating lymphocytes (TIL), most of which are cytotoxic T cells. B lymphocytes’ aggregates are

On -hereditary Sets and Consequences of the Axiom of Choice

On -hereditary Sets and Consequences of the Axiom of Choice