Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review.

PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

Breast Cancer Screening and Prophylactic Mastectomy for High-Risk Women in Romania.

Breast cancer remains a significant contributor to morbidity and mortality within oncology. Risk factors, encompassing genetic and environmental influences, significantly contribute to its prevalence. While germline mutations, notably within the BRCA genes, are commonly associated with heightened breast cancer risk, a spectrum of other variants exists among affected individuals. Diagnosis relies on imaging techniques, biopsies, biomarkers, and genetic testing, facilitating personalised risk assessment through specific scoring systems. Breast cancer screening programs employing mammography and other imaging modalities play a crucial role in early detection and management, leading to improved outcomes for affected individuals. Regular screening enables the identification of suspicious lesions or abnormalities at earlier stages, facilitating timely intervention and potentially reducing mortality rates associated with breast cancer. Genetic mutations guide screening protocols, prophylactic interventions, treatment modalities, and patient prognosis. Prophylactic measures encompass a range of interventions, including chemoprevention, hormonal inhibition, oophorectomy, and mastectomy. Despite their efficacy in mitigating breast cancer incidence, these interventions carry potential side effects and psychological implications, necessitating comprehensive counselling tailored to individual cases.

A New Frameshift Mutation of PTEN Gene Associated with Cowden Syndrome-Case Report and Brief Review of the Literature.

Cowden syndrome (CS) is a rare disease that was first described in 1963 and later included in the large group of genodermatoses. It is the most common syndrome among the PTEN-associated hamartomatous tumor syndromes (PHTS). CS has an autosomal dominant inheritance pattern, with increased penetrance and variable expressivity, making early diagnosis difficult. Mutations in the PTEN gene (phosphatase and TENsin homolog) are involved in its pathogenesis, involving many organs and systems originating in the three embryonic layers (ectodermum, endodermum, and mesodermum). The consequence is the development of hamartomatous lesions in various organs (brain, intestines, thyroid, oropharyngeal cavity, colon, rectum, etc.). Multiple intestinal polyps are common in patients with CS, being identified in over 95% of patients undergoing colonoscopy. The authors describe the case of a patient who presented the first signs of the disease at 3 ½ years (tonsil polyp) but was diagnosed only at the age of 20 following a colonoscopy that revealed hundreds of intestinal polyps, suggesting further molecular testing. A heterozygous frameshift mutation was identified in the PTEN gene, classified as a potentially pathogenic variant (c.762del.p(Val255*)). The authors present this case to highlight the path taken by the patient from the first symptoms to the diagnosis and to emphasize the clinical aspects of this mutational variant that have still not been identified in other patients with this syndrome.

Hereditary Breast Cancer in Romania-Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country.

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018-2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

Association between IL-17F, IL-17RA Gene Polymorphisms and Response to Biological Drugs in Psoriasis and Beyond.

Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.

Molecular basis and therapeutic targets in prostate cancer: A comprehensive review.

Prostate cancer is one of the most significant causes of morbidity and mortality in male patients. The incidence increases with age, and it is higher among African Americans. The occurrence of prostate cancer is associated with many risk factors, including genetic and hereditary predisposition. The most common genetic syndromes associated with prostate cancer risk are BRCA-associated hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. Local-regional therapy, i.e., surgery is beneficial in early-stage prostate cancer management. Advanced and metastatic prostate cancers require systemic therapies, including hormonal inhibition, chemotherapy, and targeted agents. Most prostate cancers can be treated by targeting the androgen-receptor pathway and decreasing androgen production or binding to androgen receptors (AR). Castration-resistant prostate cancer (CRPC) usually involves the PI3K/AKT/mTOR pathway and requires targeted therapy. Specific molecular therapy can target mutated cell lines in which DNA defect repair is altered, caused by mutations of BRCA2, partner and localizer of BRCA2 (PALB2), and phosphatase and tensin homolog (PTEN) or the transmembrane protease serine 2-ERG (TMPRSS2-ERG) fusion. Most benefits were demonstrated in cyclin dependent-kinase 12 (CDK12) mutated cell lines when treated with anti-programmed cell death protein 1 (PD1) therapy. Therapies targeting p53 and AKT are the subject of ongoing clinical trials. Many genetic defects are listed as diagnostic, prognostic, and clinically actionable markers in prostate cancer. Androgen receptor splice variant 7 (AR-V7) is an important oncogenic driver and an early diagnostic and prognostic marker, as well as a therapeutic target in hormone-resistant CRPC. This review summarizes the pathophysiological mechanisms and available targeted therapies for prostate cancer.

Do Polymorphisms of the TERT, GSTM1, and GSTT1 Genes Increase Laryngeal Cancer Susceptibility in Smokers of Romanian Descent?

Background and Objectives: The aim of this study was to investigate the association between smoking status and single-nucleotide polymorphism in candidate genes that had a known association with smoking-related tumors in previous studies and to explore their link to laryngeal cancer risk in a population of northern Romanian descent. The genes selected have key functions in xenobiotic metabolism (GSTs: the glutathione S-transferases family: GSTM1 and GSTT1) and chromosomal management (TERT). Materials and Methods: The genotype frequencies of TERTRs2736100 and the GST subfamilies (GSTM1 and GSTT1) were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The relationship between the polymorphisms and the risk of laryngeal cancer was analyzed in a retrospective case-control study of 92 laryngeal cancer cases and 101 controls, all of whom were smokers. Results: Subjects presenting the GSTT1-null variant had a two-fold increase in risk (OR = 2.05, 95% CI = 1.07-3.95, p = 0.02). While no individual risk was observed for the TERTRs2736100 polymorphism, stratification based on gender revealed a nine-fold increase in risk for carriers of the "C" allele in the heterozygote variant who were male (OR = 9, 65% CI = 3.51-26.51, p = 0.0000). Conclusions: The results showed that the GSTT1-null genotype and the mutant heterozygote variant of TERTRs2736100 genes may play a significant role in laryngeal cancer susceptibility in subjects of northern Romanian descent. There may be no association between the susceptibility to laryngeal carcinoma and the GSTM1 polymorphism. The results could not confirm the carcinogenic influence smoking has on laryngeal cancer development for the studied polymorphisms.

Influence of vitamin D receptor polymorphism rs2228570 on pathological scarring.

The physiological process of scarring is a common denominator of interest in a plethora of medical specialties. The molecular basis whereby this process results in pathological scarring for some individuals is poorly understood at present, with clues pointing towards individual predisposition for pathological scarring. Vitamin D and its subsequent pathway plays a key role in skin metabolism and homeostasis, with alterations in the level of vitamin D receptor (VDR) seen within pathological scars. The present study investigated the role of the rs2228570 polymorphism of VDR with regards to scar formation and evolution in a group of 71 female patients recovering from Caesarian section. Blood samples were taken at the time of surgery, and the follow-up was collected remotely at 3 and 6 months after surgery. The rs2228570 polymorphism was investigated using an RFLP-PCR protocol. The results demonstrated that the CC genotype, in combination with the Patient Observer Scar Assessment Scale (POSAS) and SCAR scores are associated with pathological scarring, with more studies being necessary to draw a firm conclusion.

First documented case of Myhre syndrome in Romania: A case report.

Myhre syndrome is a rare genetic autosomal dominant connective tissue disorder, characterized by developmental delay, characteristic facial features, various bone and joint abnormalities, distinctive cardiovascular, ophthalmological and ear, nose and throat (ENT) manifestations, in association with mild to moderate intellectual disability and autism or autism spectrum disorder-like behaviour. The diagnosis of Myhre syndrome is established corroborating the clinical findings with SMAD4 heterozygous mutation identified in the majority of the patients. SMAD4 gene mutations result in abnormal TGF-ß signalling in several cell types, which affects the development of several body systems and leads to the specific phenotype of Myhre syndrome. We herein report the case of an 18-year-old female patient who was diagnosed at the age of 17 years with Myhre syndrome, the first documented case of this syndrome in Romania. Sequence analysis of protein-coding genes using whole-exome analysis identified a 'de novo', heterozygous missense variant of SMAD4, c.1498A>G, p. (Ile500Val), which is pathogenic for Myhre syndrome. Although this condition is rare, a series of particularities were identified in the present case, consisting of severe allergic reactions, recurrent ENT tumour development and delayed dental eruption, which have not been described in Myhre syndrome to date, to the best of the authors' knowledge.

Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients and the Role of Hepatitis B Surface Antigen (HBsAg).

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Hepatitis B virus (HBV) infection is among the main risk factors for HCC. The risk of HCC is not eliminated completely after viral suppression, due to HBV DNA integrated into human chromosomes. Cirrhosis, HBV viral DNA levels, age, male gender, the immune response of the host against HBV, and a combination of obesity and diabetes are among the main risk factors for HCC. Active viral replication and long-standing active disease with inflammation are associated with a higher risk of HCC. Treatment of HBV with nucleos(t)ide analogues (NAs) decreased HCC risk by effectively decreasing viral load and inflammation. Similar risk factors have been reported in hepatitis B patients after seroclearance. Studies have reported decreased risk of HCC after seroclearance, but there were also conflicting results from a few studies indicating no difference in risk of developing HCC. The difference in HCC rates could be because of other factors such as coinfection, occult HBV infection, family history, HBV genotype, and other comorbidities. Due to the persistent risk of HCC after seroclearance, HCC surveillance is critical for early detection, especially in high-risk patients. However, long-term studies might be needed to further validate the results.

Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study.

BACKGROUND & AIMS: Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). METHODS: We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. RESULTS: Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19. CONCLUSIONS: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084.

Role of Adiponectin and Tumor Necrosis Factor-Alpha in the Pathogenesis and Evolution of Type 1 Diabetes Mellitus in Children and Adolescents.

Type 1 diabetes mellitus (T1DM) is a complex condition caused by the destruction of pancreatic beta cells by autoimmune mechanisms. As a result, insulin deficiency and subsequent hyperglycemia occur. The aim of the present study is to investigate the role of adiponectin and tumor necrosis factor alpha (TNF-α) in the development of T1DM. The study is designed as an observational case-control study, involving 52 diabetic patients and 66 controls. Z scores for Body Mass Index (BMI), weight, height, and adiponectin and TNF-α serum levels were assessed in both groups. The T1DM group had significantly higher TNF-α levels and a significantly higher proportion of high-risk patients for inflammation based on TNF-α values as compared to the control group, while both groups had statistically similar adiponectin levels and a similar proportion of high/medium-risk patients based on adiponectin values. TNF-α plays a significant role in the pathogenesis and evolution of T1DM and it may represent an additional marker of disease progression, as well as a potential target of immunotherapeutic strategies. In the present study, no statistically significant differences were recorded in adiponectin levels neither in diabetic patients and controls, nor in high/medium severity risk diabetic patients.

Do we know enough about the genetic involvement in laryngeal cancer susceptibility and prognostic outcome?

INTRODUCTION: Advances in molecular biology have opened the door to a wide range of research material through the usage of genetic testing on certain variables within the human genome known as single-nucleotide polymorphisms (SNPs).The purpose of this article is to present a review on the influence variants within SNPs have on the outcome of laryngeal cancer when associated with different variables, such as external toxins or survival rate. Amongst these toxins, the most frequent and most studied have been alcohol and tobacco consumption, with a proven increased rate of overall cancer risk within the aero-digestive tract. MATERIALS AND METHODS: The review was realized utilizing available studies on the subject of genetic polymorphisms analysis of deoxyribonucleic acid (DNA) samples using polymerase chain reaction (PCR) assays and laryngeal cancer published in the PubMed database. RESULTS: Statistical analysis of 262 polymorphisms shows a predominantly positive association between two genetic variants of the human genome (mutant homozygote and heterozygote) and cancer risk with significant influence on patient outcome and survival. Genotype combinations were divided into two categories depending on the individual 'at risk' and 'protective' allele within the loci of each inherited gene block. Amongst the genes involved with aero-digestive cancers, the most studied were those belonging to the xenobiotic metabolism, nucleotide excision repair (NER) and DNA repair pathways. The presence of toxins has a distinct cumulative effect within the genotype-phenotype relationship, which further influences the presence of malignancy depending on the adaptability of each individual genome. CONCLUSIONS: Laryngeal cancer evolution is linked to inherited risk factors found within the genetic code. Most studied were the genes belonging to NER pathways, DNA repair and xenobiotic metabolism, which all favored mutant homozygote and heterozygote variants, as high risk factors. Only five articles focused on overall survival rates with insufficient results to undisputedly predict the risk variants. The consumption of external toxins has a positive effect on the overall cancer risk in consumers. Most articles affirmed further evaluation or replication was needed in a larger scale population to conclusively validate their results.

Psoriasis: Association of interleukin-17 gene polymorphisms with severity and response to treatment.

Psoriasis is a chronic, inflammatory disease with a complex pathogenesis that is not yet fully understood. Although it is a multifactorial disease, the genetic factor has a major role in the pathogenesis of psoriasis. Genome wide association studies have identified over 50 genetic loci associated with psoriasis risk. Beside TNF-α or IL-23, the IL-17 family is a newer group that has proven implications in the pathogenesis of psoriasis. The most important members of the family, with pro-inflammatory qualities, are IL-17A and IL-17F. These interleukins are produced by a varied number of cells, but by far the most important are Th17 cells. Of the patients 20-30% present moderate-to-severe psoriasis, therefore, systemic medication (phototherapy, methotrexate, cyclosporine, acitretin or biologic agents) is mandatory. The necessity of an individualized treatment plan, for each patient, is imperative in order to establish the best strategy for non-responders to classical treatment or to other biologic treatments. The discovery of Th17 pathway improved the treatment and prognosis of psoriasis. Anti-psoriatic agents against IL-17 or its receptors are a novel group of biologic agents; these include ixekizumab, secukinumab and brodalumab. Polymorphisms of IL-17 family have been correlated with the severity and response to treatment in psoriasis, and also with the risk of inflammatory, infectious, autoimmune or neoplastic pathologies. The significant difference in the presence or absence of susceptibility loci in different population is due to genetic background and environmental factors that have a major impact on disease predisposition. In this study, we reviewed the importance and influence of the IL-17 polymorphisms as predictors of response to treatment and severity of the disease.

Multi gene panel testing for hereditary breast cancer - is it ready to be used?

Breast cancer is one of the most common malignancies and the leading cause of death among women worldwide. About 20% of breast cancers are hereditary. Approximately 30% of the mutations have remained negative after testing BRCA1/2 even in families with a Mendelian inheritance pattern for breast cancer. Additional non-BRCA genes have been identified as predisposing for breast cancer. Multi gene panel testing tries to cover and explain the BRCA negative inherited breast cancer, improving efficiency, speed and costs of the breast cancer screening. We identified 23 studies reporting results from individuals who have undergone multi gene panel testing for hereditary breast cancer and noticed a prevalence of 1-12% of non-BRCA genes, but also a high level of variants of uncertain significance. A result with a high level of variants of uncertain significance is likely to be more costly than bring benefits, as well as increase the anxiety for patients. Regarding further development of multi gene panel testing, more research is required to establish both the optimal care of patients with cancer (specific treatments like PARP inhibitors) and the management of unaffected individuals (chemoprevention and/or prophylactic surgeries). Early detection in these patients as well as prophylactic measures will significantly increase the chance of survival. Therefore, multi gene panel testing is not yet ready to be used outside clear guidelines. In conclusion, studies on additional cohorts will be needed to better define the real prevalence, penetrance and the variants of these genes, as well as to describe clear evidence-based guidelines for these patients.

Comparison of the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo).

PURPOSE: To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo). METHODS: MoCo PET/DCE-MRI of the upper abdomen was acquired in 44 consecutive oncologic patients and compared with non-MoCo PET/MRI. SUVmax and MTV of FDG-avid upper abdominal malignant lesions were assessed on MoCo and non-MoCo PET images. Image quality was compared between MoCo DCE-MRI and non-MoCo CE-MRI, and between fused MoCo PET/MRI and fused non-MoCo PET/MRI images. RESULTS: MoCo PET resulted in higher SUVmax (10.8 ± 5.45) than non-MoCo PET (9.62 ± 5.42) and lower MTV (35.55 ± 141.95 cm3) than non-MoCo PET (38.11 ± 198.14 cm3; p < 0.005 for both). The quality of MoCo DCE-MRI images (4.73 ± 0.5) was higher than that of non-MoCo CE-MRI images (4.53±0.71; p = 0.037). The quality of fused MoCo-PET/MRI images (4.96 ± 0.16) was higher than that of fused non-MoCo PET/MRI images (4.39 ± 0.66; p < 0.005). CONCLUSION: MoCo PET/MRI provided qualitatively better images than non-MoCo PET/MRI, and upper abdominal malignant lesions demonstrated higher SUVmax and lower MTV on MoCo PET/MRI.

Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases - the significance of the histopathological examination.

UNLABELLED: Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen-vascular and other autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute otomastoiditis. CASE REPORTS: The present report describes our experience with three such cases initially misdiagnosed. Their predominating symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) in one case, middle ear tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical inflammatory states of the ear resolved. CONCLUSIONS: As a group, systemic diseases of the middle ear and temporal bone are uncommon, but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic examination of the affected tissue, required for an accurate diagnosis and effective treatment.

XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

BACKGROUND AND AIMS: Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. METHODS: We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. CONCLUSION: In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

Direct costs of care for hepatocellular carcinoma in patients with hepatitis C cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) is the commonest cause of hepatocellular carcinoma (HCC) in the United States. The benefits of HCV therapy may be measured in part by the prevention of HCC and other complications of cirrhosis. The true cost of care of the HCV patient with HCC is unknown. METHODS: One hundred patients were randomly selected from a cohort of all HCC patients with HCV at a US transplant center between 2003 and 2013. Patients were categorized by the primary treatment modality, Barcelona class, and ultimate transplant status. Costs included the unit costs of procedures, imaging, hospitalizations, medications, and all subsequent care of the HCC patient until either death or the end of follow-up. Associations with survival and cost were assessed in multivariate regression models. RESULTS: Overall costs included a median of $176,456 (interquartile range [IQR], $84,489-$292,192) per patient or $6279 (IQR, $4043-$9720) per patient-month of observation. The median costs per patient-month were $7492 (IQR, $5137-$11,057) for transplant patients and $4830 for nontransplant patients. The highest median monthly costs were for transplant patients with Barcelona A4 disease ($11,349) and patients who received chemoembolization whether they underwent transplantation ($10,244) or not ($8853). Transarterial chemoembolization and radiofrequency ablation were independently associated with a 28% increase and a 22% decrease in costs, respectively, with adjustments for the severity of liver disease and Barcelona class. CONCLUSIONS: These data represent real-world estimates of the cost of HCC care provided at a transplant center and should inform economic studies of HCV therapy.