Thyroglossal Duct Lipoma: A Case Report and a Systematic Review of the Literature for Its Management

Thyroglossal duct (TGD) remnants in the form of cysts or fistulas usually present as midline neck masses and they are removed along with the central body of the hyoid bone (Sistrunk’s procedure). For other pathologies associated with the TGD tract, the latter operation might be not necessary. In the present report, a case of a TGD lipoma is presented and a systematic review of the pertinent literature was performed. We present the case of a 57-year-old woman with a pathologically confirmed TGD lipoma who underwent transcervical excision without resecting the hyoid bone. Recurrence was not observed after six months of follow-up. The literature search revealed only one other case of TGD lipoma and controversies are addressed. TGD lipoma is an exceedingly rare entity whose management might avoid hyoid bone excision

Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However, the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking male was diagnosed with anaplastic lymphoma kinase -positive pulmonary adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in complete objective response in the thorax and partial response in the abdomen, but after 8 months of therapy the patient acquired resistance and progressed. Biopsies from new metastases revealed development of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations concomitant with the original anaplastic lymphoma kinase gene rearrangement and without signs of anaplastic lymphoma kinase fusion gene amplification or secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver mutations, usually considered mutually exclusive, may coexist in advanced non-small cell lung carcinoma that becomes resistant to crizotinib, presumably because heterogeneous tumor clones utilize epidermal growth factor receptor and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by crizotinib. The identification of new targetable somatic mutations by tumor re-biopsy may help clarify the mechanism behind the development of the acquired crizotinib resistance and pave the way for combined strategies involving multiple targeted therapies

How has peritoneal dialysis changed over the last 30 years: experience of the Verona dialysis center

The last decade has witnessed considerable improvement in dialysis technology and changes in clinical management of patients in peritoneal dialysis (PD) with a significant impact on long term clinical outcomes. However, the identification of factors involved in this process is still not complete.METHODS:Therefore, to assess this objective, we retrospectively analyzed clinical records of 260 adult patients who started PD treatment from 1983 to 2012 in our renal unit. For the analysis, we divided them into three groups according to the time of starting dialysis: GROUP A (n: 62, 1983-1992), GROUP B (n: 66, 1993-2002) and GROUP C (n: 132, 2003 to 2012).RESULTS:Statistical analysis revealed that patients included in the GROUP C showed a reduction in mean patients' age (p = 0.03), smoking habit (p = 0.001), mean systolic blood pressure (p < 0.0001) and an increment in hemoglobin levels (p < 0.0001) and residual diuresis (p = 0.016) compared to the other two study groups. Additionally, patients included in GROUP C, mainly treated with automated peritoneal dialysis, showed a reduced risk of all-causes mortality and a decreased risk to develop acute myocardial infarction and cerebrovascular disease. Patients' age, diabetes mellitus and smoking habit were all positively associated with a significant increased risk of mortality in our PD patients, while serum albumin levels and residual diuresis were negatively correlated.CONCLUSIONS:Therefore, the present study, revealed that in the last decade there has been a growth of our PD program with a concomitant modification of our patients' characteristics. These changes, together with the evident technical advances, have caused a significant improvement of patients' survival and a decrement of the rate of hospitalization. Moreover, it reveals that our pre-dialysis care, modifying the above-mentioned factors, has been a major cause of these clinical improvements

Downregulation of nuclear-encoded genes of oxidative metabolism in dialyzed chronic kidney disease patients.

BACKGROUND:Mitochondria, essential eukaryotic cells organelles defined as the "powerhouse of the cell" because of their ability to produce the vast majority of energy necessary for cellular metabolism, may have a primary role in the oxidative stress-related intracellular machinery associated to chronic kidney disease (CKD).METHODS:To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in peritoneal dialysis (PD, n\u200a=\u200a15) using several bio-molecular methodologies.RESULTS:RT-PCR experiments demonstrate that the expression level of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1\u3b1) and nuclear respiratory factor-1 (NRF-1), two genes primarily involved in mitochondrial biogenesis and functions, were significantly hypo-expressed in peripheral blood mononuclear cells of PD patients compared to healthy subjects (HS, n\u200a=\u200a15). Additionally, mRNA levels of several PGC1-\u3b1 downstream target genes (TFAM, COX6C,COX7C, UQCRH and MCAD) were profoundly down-regulated in PD cells. TFAM protein analysis confirmed gene-expression results. High plasmatic concentration of Malondialdehyde found in PD patients, confirmed the contribution of the oxidative stress to these biological effects. Finally, Nuclear factor erythroid-derived 2-like 2 (NRF2 or NFE2L2), a transcription factor for numerous antioxidant/detoxifying enzymes and one of its target genes, superoxide dismutase-2 mitochondrial (SOD2) were up-regulated in PD compared to HS.CONCLUSIONS:Our results revealed, for the first time, that CKD-PD patients' PBMC, through a complex intracellular biochemical machinery, are able to modulate their mitochondrial functions probably in the attempt to reduce oxidative metabolic damage and to turn on a valuable defense cellular strategy against oxidative stress

Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study.

Objective: To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. Design: Partially retrospective cohort study. Setting: Two Italian transplantation centers. Patients: The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. Main Outcome Measures: Cumulative incidences and risk factors of the first and subsequent NMSCs. Results: Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a secondNMSCafter a median follow-up after the firstNMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. Conclusions: Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable

Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution

Ambulatory blood pressure monitoring and renal functions in children with a solitary kidney

The aim of this study is to investigate the blood pressure (BP) profile, microalbuminuria, renal functions, and relations with remaining normal kidney size in children with unilateral functioning solitary kidney (UFSK). Sixty-six children with UFSK were equally divided into three groups: unilateral renal agenesis (URA), unilateral atrophic kidney (UAK), and unilateral nephrectomy (UNP). Twenty-two age-, weight-, and height-matched healthy children were considered as a control group. The serum creatinine level and first-morning urine microalbumin and creatinine concentrations were determined by the standard methods. Also, the BP profile was determined by ambulatory blood pressure monitoring (ABPM). We found that the serum creatinine level was higher and creatinine clearance was lower in each patient groups compared to those of the control group (p < 0.05). Compared with the controls, each group of patients had mean office, 24-h, daytime, and night-time systolic and diastolic BP values similar to those of the controls (p > 0.05). An inverse correlation was found between the renal size standard deviation scores (SDS) of normal kidneys and 24-h systolic and diastolic BP load SDS in all of the patients (p < 0.05; r = −0.372, r = −0.295, respectively). The observed relationship between renal size SDS and 24-h mean arterial pressure (MAP), systolic and diastolic BP load SDS suggests that children with UFSK should be evaluated by using ABPM for the risk of hypertension

The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both <it>in vivo </it>and <it>in vitro</it>. We found in an <it>in-silico </it>search tight co-regulation between <it>matriptase </it>and <it>claudin-7 </it>expression. We have previously shown that the <it>matriptase </it>expression level decreases during colorectal carcinogenesis. In the present study we investigated whether <it>claudin-7 </it>expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue.</p> <p>Methods</p> <p>The mRNA level of <it>claudin-7 </it>(CLDN7) was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings.</p> <p>Results</p> <p>A 2.7-fold reduction in the <it>claudin-7 </it>mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p < 0.001). Reductions in the <it>claudin-7 </it>mRNA levels were also detected in mild/moderate dysplasia (p < 0.001), severe dysplasia (p < 0.01) and carcinomas (p < 0.01), compared to a control sample from the same individual. The decrease at mRNA level was confirmed at the protein level by immunohistochemical stainings.</p> <p>Conclusions</p> <p>Our results show that the <it>claudin-7 </it>mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.</p