ABSTRACT
BACKGROUND: Treatment option decisions for low-risk squamous cell carcinoma in situ (SCCIS) are hampered by a paucity of management-type-specific outcomes data. OBJECTIVE: Describe SCCIS tumor outcomes managed by watchful waiting and risk factors associated with poor cancer outcomes. MATERIALS AND METHODS: Retrospective cohort study. Setting: Single academic hospital in a rural setting. Patients: Adults with SCCIS diagnosed between January 01, 2014, and December 31, 2016. Main Outcomes and Measures: Hazard ratios (HRs) for local recurrence (LR), nodal metastases (NM), distant metastases (DM), and disease-specific death (DSD). RESULTS: A total of 411 consecutive SCCIS tumors that were considered clinically resolved at follow-up and managed with watchful waiting were included. Seventeen tumors recurred locally. No instances of NM, DM, or DSD were identified. Multivariate analysis found that solid-organ transplant recipient status conferred the highest risk of local recurrence [HR, 9.979 (95% CI, 2.249-39.69)]. Additional risk factors predicting LR include anatomic location on the vermilion lip or ear [HR, 9.744 (95% CI, 1.420-69.28)], anatomic location on the head and neck [HR, 6.687 (95% CI, 1.583-36.15)], and a biopsy with tumor extending to the deep edge [HR, 6.562 (95% CI, 1.367-39.04)]. CONCLUSION: Watchful waiting for SCCIS with a clinically resolved biopsy site has a local recurrence rate of 4%.
Subject(s)
Carcinoma, Squamous Cell , Neoplasm Recurrence, Local , Skin Neoplasms , Watchful Waiting , Humans , Watchful Waiting/statistics & numerical data , Male , Retrospective Studies , Female , Middle Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Skin Neoplasms/mortality , Risk Factors , Biopsy , Carcinoma in Situ/pathology , Carcinoma in Situ/therapy , Lymphatic Metastasis , Adult , Aged, 80 and overABSTRACT
Nevus sebaceus (NS) and scalp whorl are both benign congenital findings that have not previously been reported to occur simultaneously. In most cases, the isolated finding of a single, classic-appearing NS or a single hair whorl can be followed clinically with observation. However, the number of lesions, distribution, and size of NS along with atypical placement of a scalp hair whorl can indicate an underlying syndrome or even underlying cranial abnormalities. We present a unique case of NS arising within a hair whorl on the vertex scalp of an otherwise healthy male neonate. After ultrasound showed no vascular malformations or proliferations and no cranial extension at the site, the lesion was later treated with surgical excision at six months old per the parents' preference, thus allowing for histologic confirmation of NS. Additionally, we discuss herein the diagnostic implications, recommendations for work-up, and treatment options of NS.
Subject(s)
Caustics/poisoning , Sanguinaria/poisoning , Skin Ulcer/chemically induced , Skin Ulcer/pathology , Aged , Humans , MaleABSTRACT
OBJECTIVE: To compile current legislation of indoor tanning throughout the world and compare them with existing legislation found in 2003. DESIGN: Cross-sectional study. SETTING: International. PARTICIPANTS: All nations with legislation regarding access to indoor tanning found through web-based Internet search. MAIN OUTCOME MEASURES: Number of nations with legislation and changes to laws regarding access to indoor tanning since 2003. RESULTS: The number of countries with nationwide indoor tanning legislation restricting youth 18 years or younger increased from 2 countries in 2003 to 11 countries in 2011. Six states or territories in Australia restricted indoor tanning in all minors; a province and a region in Canada implemented youth tanning laws; and 8 states, in addition to 3 preexisting state laws, in the United States implemented indoor tanning legislation since 2003. CONCLUSION: Since 2003, access to indoor tanning has become increasingly restricted around the world.
Subject(s)
Beauty Culture/legislation & jurisprudence , Ultraviolet Rays/adverse effects , Adolescent , Child , Cross-Sectional Studies , Global Health , Humans , Melanoma/etiology , Melanoma/prevention & control , Skin Neoplasms/etiology , Skin Neoplasms/prevention & controlABSTRACT
Chromosomal translocations generating the BCR-ABL oncogene cause chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia. The BCR-ABL(T315I) mutation confers drug resistance to FDA-approved targeted therapeutics imatinib mesylate, dasatinib, and nilotinib. We tested the ability of a recombinant yeast-based vaccine expressing the T315I-mutated BCR-ABL antigen to stimulate an anti-BCR-ABL(T315I) immune response. The yeast-based immunotherapy significantly reduced or eliminated BCR-ABL(T315I) leukemia cells from the peripheral blood of immunized animals and extended leukemia-free survival in a murine model of BCR-ABL(+) leukemia compared to animals receiving sham injection or yeast expressing ovalbumin. With immunization, leukemic cells harboring BCR-ABL(T315I) were selectively eliminated after challenge with a mixed population of BCR-ABL and BCR-ABL(T315I) leukemias. In summary, yeast-based immunotherapy represents a novel approach against the emergence of cancer drug resistance by the pre-emptive targeted ablation of tumor escape mutants.
Subject(s)
Cancer Vaccines/immunology , Fusion Proteins, bcr-abl/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Amino Acid Sequence , Animals , Disease-Free Survival , Genes, MHC Class I , Immunotherapy , Leukemia, Experimental/immunology , Leukemia, Experimental/therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Molecular , Molecular Sequence Data , Protein Structure, Tertiary , Saccharomyces cerevisiae , Vaccines, Synthetic/immunologyABSTRACT
The possibility that organophosphorus (OP) compounds contribute to motor neuron disease (MND) is supported by association of paraoxonase 1 polymorphisms with amyotrophic lateral sclerosis (ALS) and the occurrence of MND in OP compound-induced delayed neuropathy (OPIDN), in which neuropathy target esterase (NTE) is inhibited by organophosphorylation. We evaluated a consanguineous kindred and a genetically unrelated nonconsanguineous kindred in which affected subjects exhibited progressive spastic paraplegia and distal muscle wasting. Affected subjects resembled those with OPIDN and those with Troyer Syndrome due to SPG20/spartin gene mutation (excluded by genetic linkage and SPG20/spartin sequence analysis). Genome-wide analysis suggested linkage to a 22 cM homozygous locus (D19S565 to D19S884, maximum multipoint LOD score 3.28) on chromosome 19p13 to which NTE had been mapped (GenBank AJ004832). NTE was a candidate because of its role in OPIDN and the similarity of our patients to those with OPIDN. Affected subjects in the consanguineous kindred were homozygous for disease-specific NTE mutation c.3034A-->G that disrupted an interspecies conserved residue (M1012V) in NTE's catalytic domain. Affected subjects in the nonconsanguineous family were compound heterozygotes: one allele had c.2669G-->A mutation, which disrupts an interspecies conserved residue in NTE's catalytic domain (R890H), and the other allele had an insertion (c.2946_2947insCAGC) causing frameshift and protein truncation (p.S982fs1019). Disease-specific, nonconserved NTE mutations in unrelated MND patients indicates NTE's importance in maintaining axonal integrity, raises the possibility that NTE pathway disturbances contribute to other MNDs including ALS, and supports the role of NTE abnormalities in axonopathy produced by neuropathic OP compounds.
Subject(s)
Axons/physiology , Carboxylic Ester Hydrolases/genetics , Motor Neuron Disease/genetics , Amino Acid Sequence , Chromosome Mapping , Female , Genetic Linkage , Humans , Male , Molecular Sequence Data , Mutation , PedigreeABSTRACT
BACKGROUND: Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that occur spontaneously while at rest and following caffeine or alcohol consumption. Previously, we and others identified a locus for autosomal dominant PDC on chromosome 2q33-2q35. OBJECTIVE: To identify the PDC gene. DESIGN: Analysis of PDC positional candidate genes by exon sequencing and reverse transcription-polymerase chain reaction. SETTING: Outpatient clinical and molecular genetic laboratory at a university hospital. Patients Affected (n = 12) and unaffected (n = 26) subjects from 2 unrelated families with PDC and 105 unrelated control subjects. RESULTS: We identified missense mutations in the myofibrillogenesis regulator gene (MR-1) in affected subjects in 2 unrelated PDC kindreds. These mutations were absent in control subjects and caused substitutions of valine for alanine at amino acid positions 7 and 9. The substitutions disturb interspecies conserved residues and are predicted to alter the MR-1 gene's amino-terminal alpha helix. The MR-1 exon containing these mutations (exon 1) was expressed only in the brain, a finding that explains the brain-specific symptoms of subjects with these mutations. CONCLUSIONS: Although MR-1 gene function is unknown, the precedence of ion channel disturbance in other episodic neurologic disorders suggests that the pathophysiologic features of PDC also involve abnormal ion localization. The discovery that MR-1 mutations underlie PDC provides opportunities to explore this condition's pathophysiologic characteristics and may provide insight into the causes of other paroxysmal neurologic disorders as well as the neurophysiologic mechanisms of alcohol and caffeine, which frequently precipitate PDC attacks.
Subject(s)
Athetosis/genetics , Chorea/genetics , Dystonia/genetics , Genes, Regulator/physiology , Muscle Development/genetics , Mutation , Athetosis/physiopathology , Chorea/physiopathology , Chromosomes, Human, Pair 2/genetics , Dystonia/physiopathology , Female , Genes, Regulator/genetics , Genetic Linkage/genetics , Haplotypes/genetics , Humans , Male , Pedigree , Physical Chromosome MappingABSTRACT
BACKGROUND: Distal myopathies (MPDs) are genetically heterogeneous. Genetic causes within this subgroup of muscle disorders remain largely unknown. An MPD linked to chromosome 14q11-q13 (MPD1) is rare, and to our knowledge, only one family with definitive linkage has been described. OBJECTIVE: To describe the results of clinical and genetic analysis of the second kindred with MPD1. PATIENTS AND METHODS: We have identified a family with an MPD segregating in an autosomal dominant fashion. We tested linkage to previously identified genetic loci on chromosomes 2p, 2q, and 14q. The coding sequence of PABP2 (the polyadenylate-binding protein 2 gene) was analyzed. RESULTS: Every affected individual had selective weakness of foot extensors, with the average age of symptom onset at 20 years. Some patients also had proximal weakness, but none had signs of finger or hand extensor muscle involvement, even in advanced stages of the disease. Two typically affected individuals had signs of idiopathic dilated cardiomyopathy. Genetic analysis detected a tight linkage to chromosome 14q11-q13. Recombination at the telomeric end of the 14q11-q13 locus was found in an unaffected individual who was not considered to be at risk, potentially reducing the locus interval by 2 centimorgans. No mutations in the PABP2 gene were identified. CONCLUSIONS: To our knowledge, our described family is only the second known kindred with a chromosome 14-linked MPD in whom the linkage has been unequivocally established. We did not detect signs of involvement of hand or finger extensors and neck muscles, seen in the original family with MPD1. The degree and frequency of proximal weakness seem to be more prominent than in other patients with MPD1. Haplotype analysis suggests that the gene is located between polymorphic microsatellite markers D14S283 and D14S1034 on chromosome 14q11-q13. The presence of cardiomyopathy in some affected individuals may help in the identification of candidate genes.