Cause of death in squamous cell carcinoma of the head and neck. An autopsy study on 31 patients.

A series of 31 autopsied patients, with a history of head and neck squamous cell carcinoma is reported, with the emphasis on the cause of death. There were 26 males and 5 females; mean age being 64 years (range 44-88 years). Locoregional disease (LRD) was the cause of death in 19 patients (61%) and was present in 2 patients dying of an unrelated cause. Distant metastasis (DM) was found in 8 patients (26%) but had caused death in only 1 of them. A shorter survival time for patients with DM than for those without (8 months versus 13 months) indicates that DM is established early in the course of the disease. Therefore, a longer survival time will not result in an increase in DM and we infer that a better locoregional control will also not result in a real increase in DM but only in an apparent one, due to a shift of cause of death from LRD to DM in a group of patients that formerly would have died of LRD before the already present DM had become manifest.     

Longitudinal Study of Extended-Spectrum-β-Lactamase- and AmpC-Producing Enterobacteriaceae in Household Dogs

A longitudinal study was performed to (i) investigate the continuity of shedding of extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae in dogs without clinical signs, (ii) identify dominant plasmid-mediated ESBL genes, and (iii) quantify ESBL-producing Enterobacteriaceae in feces. Fecal samples from 38 dogs were collected monthly for 6 months. Additional samples were collected from 7 included dogs on a weekly basis for 6 weeks. Numbers of CFU per gram of feces for non-wild-type Enterobacteriaceae were determined by using MacConkey agar supplemented with 1 mg/liter cefotaxime (MCC), and those for total Enterobacteriaceae were determined by using MacConkey agar. Cefotaxime-resistant isolates were screened by PCR and sequence analysis for the presence of bla_CTX-M, bla_CMY, bla_SHV, bla_OXA, and bla_TEM gene families. Bacterial species were identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis. PCR-negative isolates were tested by a double-disk synergy test for enhanced AmpC expression. A total of 259 samples were screened, and 126 samples were culture positive on MCC, resulting in 352 isolates, 327 of which were Escherichia coli. Nine dogs were continuously positive during this study, and 6 dogs were continuously negative. Monthly or weekly shifts in fecal shedding were observed for 23 dogs. Genotyping showed a large variety of ESBL genes and gene combinations at single and multiple consecutive sampling moments. The ESBL genes bla_CTX-M-1, bla_CTX-M-14, bla_CTX-M-15, bla_SHV-12, and bla_CMY-2 were most frequently found. The mean number of CFU of non-wild-type Enterobacteriaceae was 6.11 × 10⁸ CFU/g feces. This study showed an abundance of ESBL-producing Enterobacteriaceae in dogs in the Netherlands, mostly in high concentrations. Fecal shedding was shown to be highly dynamic over time, which is important to consider when studying ESBL epidemiology.     

A gene expression profile for non-smoking and non-drinking patients with head and neck cancer

Oral Diseases (2012) 18 , 178–183 Objective: A small subset of patients with head and neck squamous cell carcinoma are non‐smoking and non‐drinking and have distinct clinical characteristics. We aimed to identify a possible different genetic profile for these patients when compared with their smoking and drinking counterparts. Materials and Methods: The gene expression data previously detected from primary tumors located in the oral cavity and oropharynx, using DNA microarray was analyzed for their differential expression between non‐smoking and non‐drinking patients (n = 15) and smoking and drinking patients (n = 89). Student’s T‐test (P < 0.05) and 10‐fold cross‐validation procedure (100 times repeated) were performed to determine differentially expressed genes. Results: Non‐smoking and non‐drinking patients were older, mostly female and had oral cavity‐localized tumors, whereas smoking and drinking patients were younger male patients with 81% oral cavity and 19% oropharynx tumors. A set of 49 differentially expressed genes were detected. Among others, seven genes related to interferon‐γ were upregulated and two genes linked to NFKB pathway were downregulated. Conclusions: Differentially expressed genes in non‐smoking and non‐drinking patients possibly indicate the presence of a different cellular response to carcinogenic events in these patients. Further studies are warranted to validate this gene set and explore possible therapeutic implications to improve prognosis for these patients.     

Electrocautery therapy for refractory anastomotic strictures of the esophagus

BACKGROUND: Anastomotic esophageal stenoses after esophageal resection are common and sometimes are refractory to Savary bougie dilation. The efficacy of electrocautery needle-knife treatment in these patients is described. METHODS: Twenty patients with a refractory anastomotic stricture of the esophagus were treated with electrocautery and were followed for 12 months. All patients had recurrence of dysphagia despite repeated bougienage. OBSERVATIONS: All 12 patients with a stricture shorter than 1 cm remained without dysphagia after a single treatment. In all 8 patients with a long-segment stenosis of 1.5 to 5 cm, dysphagia recurred, and a mean of 3 treatments were necessary. The interval between electrocautery treatments was significantly longer compared with bougienage. There were no complications. The body weight of all patients increased. CONCLUSIONS: Electrocautery seems to be a good single-treatment modality for refractory short-segment anastomotic strictures, whereas longer-segment stenoses appear to require repeated treatment sessions before similar results are obtained.     

A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome)

Rump P, Niessen RC, Verbruggen KT, Brouwer OF, de Raad M, Hordijk R. A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome). Opitz–Kaveggia syndrome is a rare X‐linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty‐three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz–Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.     

Kohlschütter–Tönz Syndrome: Mutations in ROGDI and Evidence of Genetic Heterogeneity

Kohlschütter–Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschütter in 1974, and to date, only a total of 20 pedigrees have been reported. The genetic etiology of KTS remained elusive until recently when mutations in ROGDI were independently identified in three unrelated families and in five likely related Druze families. Herein, we report a clinical and genetic study of 10 KTS families. By using a combination of whole exome sequencing, linkage analysis, and Sanger sequencing, we identify novel homozygous or compound heterozygous ROGDI mutations in five families, all presenting with a typical KTS phenotype. The other families, mostly presenting with additional atypical features, were negative for ROGDI mutations, suggesting genetic heterogeneity of atypical forms of the disease.     

A 3-base pair deletion,c.9711_9713del,in DMD results in intellectual disability without muscular dystrophy

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy.     

A 649 kb microduplication in 1p34.1, including POMGNT1, in a patient with microcephaly,coloboma and laryngomalacia; and a review of the literature

We report on a male patient with intra-uterine growth retardation, microcephaly, coloboma, laryngomalacia and developmental delay. Array CGH analysis revealed a 649 kb duplication on chromosome 1p34.1. Only five patients with overlapping duplications have been reported thus far. Ten known genes are located in the duplicated region, including the POMGNT1 gene encoding for O-mannose beta-1,2-N-acetylglucosaminyltransferase. This gene, mutated in muscle–eye–brain disease, might be causative for the observed phenotype in our patient.