What do you really need to know about imaging of peritoneal metastases? Radiologists...
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What do you really need to know about imaging of peritoneal metastases? Radiologists...
Read more on AuntMinnieEurope.com
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Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of keratinocytes. Mutations in nine genes including PNPLA1 are known to cause non-syndromic forms of ARCI. To date, only ten distinct pathogenic mutations in PNPLA1 have been reported.
To identify new causative PNPLA1 mutations, we screened genetically unresolved cases including our ARCI collection comprising more than 700 families. Here, we report on 16 novel mutations present in patients from 17 families.
The screening for mutations was performed either by direct Sanger sequencing or in combination with a multi gene panel, followed by sequence and mutation analysis.
While all previously reported mutations and most of our novel mutations are located within the core patatin domain, here we report on five novel PNPLA1 mutations, which are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation.
We estimate the frequency of PNPLA1 mutations amongst ARCI patients to around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotype variation in a small percentage of patients with PNPLA1 mutations.
The variability of the clinical manifestations as well as the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.
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Mammogram: An X-ray of the breast that is taken with a device that compresses and flattens the breast. A mammogram can help a health professional decide whether a lump in the breast is a gland, a harmless cyst, or a tumor. A mammogram can cause pressure, discomfort, and some soreness that lasts for a little while after the procedure. If the mammogram result raises suspicions about cancer, a biopsy is usually the next step. The American Cancer Society and the American College of Surgeons currently recommend that a woman obtain her first, baseline, mammogram between the ages of 35 and 40. After the age of 40, a mammogram should be done yearly. Women who are at high risk for developing breast cancer may need to obtain mammograms earlier than these recommendations and at more frequent intervals.
Symptomatic adverse event (AE) monitoring is essential in cancer clinical trials to assess patient safety, as well as inform decisions related to treatment and continued trial participation. As prior research has demonstrated that conventional concordance metrics (e.g., intraclass correlation) may not capture nuanced aspects of the association between clinician and patient-graded AEs, we aimed to characterize differences in AE grading thresholds between doctors (MDs), registered nurses (RNs), and patients using the Bayesian Graded Item Response Model (GRM).
From the medical charts of 393 patients aged 26–91 (M = 62.39; 43% male) receiving chemotherapy, we retrospectively extracted MD, RN and patient AE ratings. Patients reported using previously developed Common Terminology Criteria for Adverse Events (CTCAE) patient-language adaptations called STAR (Symptom Tracking and Reporting). A GRM was fitted to calculate the latent grading thresholds between MDs, RNs and patients.
Clinicians have overall higher average grading thresholds than patients when assessing diarrhea, dyspnea, nausea and vomiting. However, RNs have lower grading thresholds than patients and MDs when assessing constipation. The GRM shows higher variability in patients’ AE grading thresholds than those obtained from clinicians.
The present study provides evidence to support the notion that patients report some AEs that clinicians might not consider noteworthy until they are more severe. The availability of GRM methodology could serve to enhance clinical understanding of the patient symptomatic experience and facilitate discussion where AE grading discrepancies exist. Future work should focus on capturing explicit AE grading decision criteria from MDs, RNs, and patients.
Leukemia cutis (LC) is a rare clinical presentation of leukemia that is associated with poor prognosisabs. To date, the value of radiotherapy (RT) for the treatment of LC remains controversial. Therefore, the aim of this study was to analyse the effectiveness of various RT doses for LC.
Between January 2000 and January 2016, 13 patients underwent RT at our institution after exhibiting progressive disease following other treatment modalities.
A total of 36 radiation courses were administered to 13 patients (8 females, 5 males) with a median age of 41 years (range 2–76). Radiation modalities included 32 focal treatments, while total skin electron beam therapy was applied to four patients. The median RT dose was 27 Gy (range 8–34). A complete response rate (CRR) to RT was achieved for 32/36 (89%) lesions (100% for AML lesions versus 33% for the other leukemias; P < 0.001). The median duration of local control (DOLC) for the entire cohort was 38 months (range 0–98), while the median survival (MS) from the time of LC presentation was 13 months (range 2.5–106). The CRR for the LC lesions treated with high-dose regimens (>26 Gy) versus low-dose regimens (≤26 Gy) was 95 versus 83%, respectively (P = 0.26), and the median DOLC was 44 months versus 10 months, respectively (P = 0.019). AML patients had a better long-term outcome than the other patients according to median DOLC (40 months versus 2 months, respectively; P < 0.001) and MS (24 versus 6 months, P = 0.004). RT was well tolerated without significant adverse events.
A radiation dose ≤26 Gy confer a comparable CRR to high-dose regimens and appears to be an effective treatment for controlling LC progression. However, radiation doses >26 Gy were associated with a longer DOLC. LC patients with underlying AML are associated with better outcome compared with other types of leukemia.
The p42.3 gene is identified recently, and the upregulated expression has been characterized in a variety of human cancers and embryonic tissues but not yet in malignant melanoma. In this study, we explored the role of p42.3 gene in the development of melanoma.
The expression of p42.3 was detected by immunohistochemistry staining of 261 cases of patient lesions, including nevi and melanoma, and its correlation with clinical pathological characteristics and prognosis was analyzed. Furthermore, a series of in vitro assays were used to investigate the biological function of p42.3 in melanoma cells.
Immunohistochemistry staining showed an elevated expression level of p42.3 in melanoma compared to nevi (P = 0.001). Statistical analysis indicated that this high level was well correlated with patients’ clinical stage (P = 0.045), but not with gender, age, clinical type, mitotic rate, and overall survival (P > 0.05). Moreover, in vitro assays showed knockdown p42.3 gene expression could inhibit the biological profiling, including proliferation, migration, and invasion of melanoma cells, and also affect PI3K/Akt pathway, MAPK pathway, and β-catenin.
This study suggests that p42.3, acting like an oncogene, is involved in the malignant transformation process of melanoma and may serve as a biomarker for diagnostic and treatment purposes.
In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC.
In this retrospective study, tissue samples from 472 Japanese patients with CRC, stratified for MSI, were analyzed to determine the prognostic value of BRAF V600E, as assessed using IHC. Mutations in 254 patients were evaluated using the direct sequencing method to check for concordance.
The frequency of MSI-H was 9.3 % (44/472), and BRAF V600E mutation was detected immunohistochemically in 8.7 % patients (41/472). The sensitivity and specificity for detection of BRAF V600E mutations by IHC were 100 % (17/17) and 98.7 % (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical tumor site (P = 0.0035), histological type (P < 0.0001), and MSI status (P < 0.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio = 1.500, P = 0.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard ratio = 2.621, P = 0.0004).
IHC using a BRAF V600E-specific antibody was useful for diagnosis and concurred with direct sequencing results. CRC cases could be stratified by combining BRAF V600E mutation and MSI status as a prognostic factor in Japanese patients.