Neoadjuvant immunotherapy in microsatellite instability-high (MSI-H) duodenal adenocarcinoma leads to pathological complete response and paves the way for new strategies.

Duodenal adenocarcinoma is a rare digestive cancer, often diagnosed at a late stage and harbours a poor prognosis. The arrival of immunotherapy has changed the prognosis of many neoplasia, including digestive adenocarcinomas with MSI-H status. Hereby, we describe three cases of MSI-H locally advanced duodenal adenocarcinoma who received neoadjuvant treatment with a PD1 inhibitor, pembrolizumab. A partial metabolic and endoscopic response was observed in all patients after 2 cycles. Duodenopancreatectomy was performed at the end of treatment (4-6 cycles), and anatomopathological analysis demonstrated pathological complete response in all patients. Our case series paves the way for prospectively exploring neoadjuvant immunotherapy in duodenal MSI-H adenocarcinoma and raises the question of organ sparing surgery in case of complete clinical response as observed in gastric and colo-rectal adenocarcinomas.

Case report: Sclerosed hemangioma of the liver: A diagnostic challenge.

Hemangiomas are the most common noncystic benign hepatic tumors and are usually incidentally discovered during routine radiological examinations. The diagnosis of hepatic hemangiomas with a typical presentation is generally easy with plain and cross-sectional imaging; however, it can be complicated when hemangiomas undergo histological changes such as fibrosis. Sclerosed hepatic hemangioma (SHH) is the extreme presentation of this fibrotic process. These atypical lesions can be misdiagnosed as primary hepatic malignancies or metastasis. Their diagnosis is established by histological examination. We report the case of a patient with an SHH, which was misdiagnosed as an intrahepatic cholangiocarcinoma. This article's aim is to draw attention to this infrequent pathology and underline the features of this benign tumor that could suggest its diagnosis prior to surgery to avoid unnecessary hepatic resections.

Complete response of a hepatocellular carcinoma with complex macrovascular invasion after combined treatment with chemoembolization and immunotherapy: a case report.

Hepatocellular carcinoma accounts for 90% of primary liver cancers and represents a growing health problem worldwide. We report the complex case of a 71 year-old patient diagnosed with a large hepatocellular carcinoma and presenting an extensive vascular invasion of the middle hepatic vein and the inferior caval vein ascending to the right atrium with no extrahepatic spread. Due to several comorbidities, a systemic treatment by tyrosine kinase inhibitors was contraindicated. After discussion at the multidisciplinary hepatology tumor board, he was referred for selective internal radiation therapy. Unfortunately, the work-up showed an important lung shunt not allowing radioembolization. No clear recommendations are available in this situation. The decision was made to propose a combination treatment by transarterial chemoembolization, that was performed using a new generation of radio-opaque microspheres loaded with doxorubicin, followed by immunotherapy. This allowed a complete response with a very good quality of life.

Optimum imaging of chronic pancreatitis.

Chronic pancreatitis is an inflammatory process of the pancreas characterized by progressive parenchyma destruction, resulting in pain and exocrine and endocrine insufficiency. In the advanced stages the diagnosis by imaging is usually straightforward, while in the early phases of the disease there can be a paucity of findings at imaging, thus making an early diagnosis challenging. Different imaging modalities can have a role in the initial diagnosis and in the longitudinal follow-up of patients affected by chronic pancreatitis, also enabling to assess the complications of the disease. Radiography, Ultrasonography, CT and MRI can all provide morphological information, and MRI with the administration of secretin can also provide functional information. The use of an appropriate technique is fundamental for optimizing the examination to the clinical question.

ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis.

Grade IV astrocytoma or glioblastoma multiforme (GBM) is one of the most aggressive and lethal tumors affecting humans. ADAR2-mediated A-to-I RNA editing, an essential post-transcriptional modification event in brain, is impaired in GBMs and astrocytoma cell lines. However, the role of ADAR2 editing in astrocytomas remains to be defined. Here, we show that ADAR2 editing rescue in astrocytomas prevents tumor growth in vivo and modulates an important cell cycle pathway involving the Skp2/p21/p27 proteins, often altered in glioblastoma. We demonstrate that ADAR2 deaminase activity is essential to inhibit tumor growth. Indeed, we identify the phosphatase CDC14B, which acts upstream of the Skp2/p21/p27 pathway, as a novel and critical ADAR2 target gene involved in glioblastoma growth. Specifically, ADAR2-mediated editing on CDC14B pre-mRNA increases its expression with a consequent reduction of the Skp2 target protein, as shown both in vitro and in vivo. We found that, compared to normal brain, both CDC14B editing and expression are progressively impaired in astrocytomas from grade I to IV, being very low in GBMs. These findings (1) demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, (2) identify ADAR2-editing enzyme as a novel candidate tumor suppressor gene and (3) provide proof of principle that ADAR2 or its substrates may represent a suitable target(s) for possible novel, more effective and less toxic approaches to the treatment of GBMs.

The cost of vision loss in Canada. 1. Methodology.

OBJECTIVE: This paper outlines the methodology used to estimate the cost of vision loss in Canada. The results of this study will be presented in a second paper. DESIGN: The cost of vision loss (VL) in Canada was estimated using a prevalence-based approach. This was done by estimating the number of people with VL in a base period (2007) and the costs associated with treating them. The cost estimates included direct health system expenditures on eye conditions that cause VL, as well as other indirect financial costs such as productivity losses. Estimates were also made of the value of the loss of healthy life, measured in Disability Adjusted Life Years or DALY's. To estimate the number of cases of VL in the population, epidemiological data on prevalence rates were applied to population data. The number of cases of VL was stratified by gender, age, ethnicity, severity and cause. The following sources were used for estimating prevalence: Population-based eye studies; Canadian Surveys; Canadian journal articles and research studies; and International Population Based Eye Studies. Direct health costs were obtained primarily from Health Canada and Canadian Institute for Health Information (CIHI) sources, while costs associated with productivity losses were based on employment information compiled by Statistics Canada and on economic theory of productivity loss. Costs related to vision rehabilitation (VR) were obtained from Canadian VR organizations. CONCLUSIONS: This study shows that it is possible to estimate the costs for VL for a country in the absence of ongoing local epidemiological studies.

The cost of vision loss in Canada. 2. Results.

OBJECTIVE: This study was conducted to provide the financial underpinnings necessary for effective planning for the provision of eye health services in Canada. Canada is facing an aging demographic and all the major eye diseases are diseases associated with aging. It is essential that we have information based on the best available data to support national and provincial vision health plans. DESIGN: The design associated with the prevalence-based approach used in this study was outlined previously in detail in The Cost of Vision Loss in Canada: Methodology. METHODS: The methods associated with the prevalence-based approach used in this study were previously outlined in detail in The Cost of Vision Loss in Canada: Methodology. RESULTS: The financial cost of VL in Canada in 2007 was estimated to be $15.8 billion per annum: $8.6 billion (54.6%) represents direct health system expenditure; $4.4 billion (28.0%) was productivity lost due to lower employment, higher absenteeism, and premature death of Canadians with VL; $1.8 billion (11.1%) was the dead weight losses (DWL) from transfers including welfare payments and taxation forgone; $0.7 billion (4.4%) was the value of the care for people with VL; $305 million (1.9%) was other indirect costs such as aids and home modifications and the bring forward of funeral costs. Additionally, the value of the lost well-being (disability and premature death) was estimated at a further $11.7 billion. In per capita terms, this amounts to a financial cost of $19370 per person with VL per annum. Including the value of lost well-being, the cost is $33704 per person per annum. CONCLUSIONS: There is a growing awareness in Canada and around the world of the impact of VL on health costs and on the economy in general. This awareness is supported by the growing number of independent studies on the cost of vision loss both nationally and globally. Because most of these studies are limited by the minimal amount of available data, the overall cost of vision loss is likely underestimated. Nevertheless, this study reports the cost of vision loss in Canada as being greater than previously reported, making the problem even more urgent to address. A comprehensive national vision health plan, that is a coordinated federal, provincial and territorial initiative dealing with all aspects of vision loss prevention, sight restoration, and vision rehabilitation is called for.

Economic impact of primary open-angle glaucoma in Australia.

BACKGROUND: Glaucoma is the World's leading cause of irreversible blindness, and poses serious public health and economic concerns. DESIGN: Review. SAMPLES: Published randomized trials and population-based studies since 1985. METHODS: We report the economic impact of primary open-angle glaucoma and model the effect of changes in detection rates and management strategies. MAIN OUTCOME MEASURES: The cost-effectiveness of different interventions to prevent vision loss from primary open-angle glaucoma was measured in terms of financial cost (Australian dollars) and disability-adjusted life years. RESULTS: The prevalence of glaucoma in Australia is expected to increase from 208 000 in 2005 to 379 000 in 2025 because of the aging population. Health system costs over the same time period are estimated to increase from $AU355 million to $AU784 million. Total costs (health system costs, indirect costs and costs of loss of well-being) will increase from $AU1.9 billion to $AU4.3 billion in Australia. CONCLUSION: Primary open-angle glaucoma poses a significant economic burden, which will increase substantially by 2025. This dynamic model provides a valuable tool for ongoing policy formulation and determining the economic impact of interventions to better prevent visual impairment and blindness from glaucoma.

Economic cost of visual impairment in Japan.

OBJECTIVE: To quantify the total economic cost of visual impairment in Japan. METHODS: A prevalence-based approach was adopted using data on visual impairment, the national health system, and indirect costs to capture the economic impact of visual impairment in 2007. RESULTS: In 2007, visual impairment affected more than 1.64 million people in Japan and cost around yen 8785.4 billion (US $72.8 billion) across the economy, equivalent to 1.7% of Japan's gross domestic product. The loss of well-being (years of life lost from disability and premature mortality) cost yen 5863.6 billion (US $48.6 billion). Direct health system costs were yen 1338.2 billion (US $11.1 billion). Other financial costs were yen 1583.5 billion (US $13.1 billion), including productivity losses, care takers' costs, and efficiency losses from welfare payments and taxes. Community care was the largest component of other financial costs and was composed of paid and unpaid services that provide home and personal care to people with visual impairment. The findings of this study are in line with those of similar studies in Australia and the United States. CONCLUSIONS: Visual impairment imposes substantial costs on society, particularly to individuals with visual impairment and their families. Eliminating or reducing disabilities from visual impairment through public awareness of preventive care, early diagnosis, more intensive disease treatment, and new medical technologies could significantly improve the quality of life for people with visual impairment and their families, while also potentially reducing national health care expenditure and increasing productivity in Japan. The results of this study should provide a first step in helping policymakers evaluate policy effects and to prioritize research expenditures.

Prevalence of visual impairment in the adult Japanese population by cause and severity and future projections.

PURPOSE: To present a comprehensive estimate of the total number of people with visual impairment in the adult Japanese population by age, gender, severity and cause, and to estimate future prevalence based on population projections and expected demographic changes. METHODS: Definitions of visual impairment used in this study were based on the United States criteria. Total visual impairment was calculated as the sum of low vision and blindness. The prevalence estimates were based on input from a number of Japanese epidemiological surveys, census material and official population projections. RESULTS: There were an estimated 1.64 million people with visual impairment in 2007 in Japan. Of these, 187,800 were estimated to be blind. The prevalence of visual impairment in Japan increased with age and half of the people with visual impairment were aged 70 years or older. The leading causes of visual impairment in Japan were glaucoma (24.3%), diabetic retinopathy (20.6%), degenerative myopia (12.2%), age-related macular degeneration (10.9%), and cataract (7.2%). These five major causes comprised three-quarters of all visual impairment. The prevalence of visual impairment was projected to increase from 1.3% of the population in 2007 to 2.0% by 2050. CONCLUSIONS: This comprehensive study presents the prevalence of total visual impairment in the adult Japanese population. The projected increases in the prevalence of visual impairment over time reflect the demographic changes of a declining and aging Japanese population. These projections highlight that the burden of disease due to visual impairment and imposed on society is likely to increase.

Cost of treating otitis media in Australia.

OBJECTIVE: Otitis media (OM) is an inflammation of the middle ear. It is very common and associated with serious complications, including hearing loss. This study aimed to estimate the treatment costs of OM in Australia and the associated burden of disease (in disability-adjusted life-years). METHODS: Little Australia-wide epidemiological information is available, so international studies in the main were used to estimate the incidence and prevalence by age and gender. These were triangulated against the available Australian data. Australian health data sets and data collected from the emergency department of a tertiary pediatric hospital were used to estimate the costs of primary care, pharmaceuticals, pathology and imaging, emergency department presentations, specialists, and admitted hospital care. RESULTS: Excluding the costs of the complications and comorbidities associated with OM, treatment costs for the disease in 2008 were between AUS$100 and 400 million. Visits to general practitioners and medicines constituted a high proportion of these costs. Antibiotic prescribing rates remain high despite clear evidence for a limited benefit from antibiotics for most OM cases and concerns regarding bacterial resistance. CONCLUSION: Treatment costs of OM in Australia are high and can only be estimated within a broad range. Further research on the links between antibiotics for OM and antibiotic resistance, and on the cost-effectiveness of prevention or amelioration of OM would be useful.

Vertebroplasty as treatment of aggressive and symptomatic vertebral hemangiomas: up to 4 years of follow-up.

INTRODUCTION: This study aimed to illustrate the validity of the treatment with vertebroplasty (VP) in patients with aggressive or symptomatic vertebral hemangioma (VH) with or without epidural extension. METHODS: From January 2003 to December 2007, 24 consecutive patients have been treated with VP, for a total of 36 vertebral bodies affected by VH: two cervical, ten dorsal, 24 lumbar. All the patients complained of a pain syndrome resistant to continuous medical medication; four of 24 patients also presented aggressive magnetic resonance features of the vertebral lesion and two patients showed also epidural extension. A unipedicular approach has been performed in 16 patients; a bipedicular approach has been performed in six, while for the cervical spine an anterior-lateral approach with manual dislocation of the carotid axis has always been performed. Bone biopsy was never done. All procedures have been carried out with local anesthesia, except for the treatment of the cervical hemangiomas which has always been performed under general anesthesia. Four vertebral bodies in the same session have been treated in one case. RESULTS: Results have been evaluated with the visual analog scale and the Oswestry Disability Index methods. In all the patients, in the following 24-72 h, a successful outcome has been observed with a complete resolution of pain symptom. Extravertebral vascular or discal cement leakage has been observed in four patients, without any onset of clinical radicular syndrome due to epidural diffusion. Clinical and radiological follow-up until 4 years has been performed in 12 patients and it showed stability of the treatment and absence of pain. CONCLUSIONS: Percutaneous treatment with VP for aggressive and symptomatic vertebral hemangiomas even with epidural extension is a valuable, mini-invasive, and quick method that allows a complete and enduring resolution of the painful vertebral symptoms without findings of fracture of a vertebral body adjacent or distant to the one treated.

A comparison of minimally invasive techniques in percutaneous treatment of lumbar herniated discs. A review.

Low back pain is the commonest spine disease causing absence from work in developed countries. Low back pain with classical irradiation along the course of the nerve root affected is more frequently due to disc disease. In 60-80% of patients with herniated disc, radicular symptoms disappear with conservative treatment after about six weeks, the remainder are treated surgically with a 2-6% of incidence of true recurrence of herniation post-intervention and with failed back surgery syndrome in 15% of cases. Recently minimally invasive techniques have developed as "alternative" treatments to surgical intervention. This review aimed to assess the pathogenesis of low back pain caused by lumbar disc hernia as a basis for action of minimally invasive techniques; to illustrate the techniques already used or currently in use, to compare them in technical guidance, indications and complications, exposing for each of them the inclusion/exclusion criteria in enrolling patients and the imaging guide technique of choice. Minimally invasive techniques can be a valuable alternative to traditional surgery with low cost, low risk of complications, easy feasibility, and in the event of failure they do not exclude subsequent surgery.

Management of vertebral re-fractures after vertebroplasty in osteoporotic patients.

SUMMARY: This study illustrates the usefulness of vertebral biopsy in osteoporotic patients previously treated with vertebroplasty (VP) who present at follow-up with a new fracture in a vertebral soma adjacent or distant from the collapsed vertebral body. Five hundred and fifty patients with osteoporotic vertebral collapse underwent a minimally invasive treatment with vertebroplasty (VP) for a total of 980 vertebral bodies. The approach was unipedicular in 520 patients and bipedicular in 30. Only cases with unclear findings at MR or CT (23 patients) were scheduled for a vertebral biopsy before VP treatment. The biopsy results were positive for haematological disease in only eight patients. A vertebral biopsy was carried out during re-treatment with VP in all patients who presented a vertebral refracture in the three month follow-up at a site adjacent to or distant from the previously treated vertebra (21 patients). We have found new fractures of adjacent vertebrae in 15 patients and new fractures of distant vertebrae in 16 patients at three month follow-up examination. Five of the 31 cases (16%) of spinal refracture, where during vertebroplasty treatment a bone biopsy and a sternal medullary aspiration had been carried out, an anatomopathological response to multiple myeloma was responsible for the refracture. It is useful to perform a spinal bone biopsy during re-treatment of the vertebroplasty procedure to rule out multiple myeloma or other disease as the cause of the new collapse in patients with osteoporotic disease presenting a new vertebral fracture in an adjacent or distant site from the previously collapsed vertebral body.

Gastrointestinal disorders in elderly patients.

Gastrointestinal disorders are common in elderly patients, and the clinical presentation, complications, and management may differ from those in younger patient. Most impairment occurs in the proximal and distal tract of the gastrointestinal system. Swallowing abnormalities with a wide span of symptoms and pelvic floor pathologies involving all the pelvic compartments are common. Acute abdomen, often from small bowel obstruction or mesenteric ischemia, can pose a diagnostic challenge, because a mild clinical presentation may hide serious visceral involvement. In this setting, the radiologist often is asked to suggest the appropriate management options and to guide the management.

Maxillofacial fibrous dysplasia: personal experience with gadoliniumenhanced magnetic resonance imaging.

PURPOSE: The authors sought to identify radiological criteria assisting in the diagnosis of craniofacial fibrous dysplasia and differential diagnosis of fibro-osseous lesions by comparing computed tomography (CT) and magnetic resonance imaging (MRI) findings and histological results in 23 patients with presumed fibrous dysplasia. MATERIALS AND METHODS: From February 2000 to March 2005, 23 patients (17 women and six men, aged 9-66 years) with facial bone disease underwent CT and MRI studies. Imaging findings were compared with the results of histological examination performed within 1 month of the radiological diagnosis. RESULTS: The combination of CT and MRI led to a presumptive diagnosis of fibrous dysplasia in all cases, but histology confirmed the diagnosis in 18 cases only. In two cases that had initially been considered cyst-like variants of fibrous dysplasia and were associated with irregular enhancement at MRI, histology characterised the lesions as single locations of multiple myeloma. In one case, targeted biopsy of areas showing intense enhancement led to a diagnosis of low-grade fibrosarcoma; in the remaining two cases, the definitive diagnoses were ossifying fibroma and myeloproliferative disease. CONCLUSIONS: MRI proved useful in differentiating fibrous dysplasia from other bone diseases, defining clinical behaviour, identifying neoplastic foci within dysplastic tissue and distinguishing benign from malignant bone lesions. The authors suggest a broader use of contrast-enhanced MRI for the diagnosis and follow-up of dysplastic lesions of the facial bones and for planning appropriate surgical treatment.

Lipomatous lesions of the head and neck region: imaging findings in comparison with histological type.

PURPOSE: Aim of the study is to demonstrate the main role of magnetic resonance imaging in the identification and characterization of lipomatous lesions of the head and neck. MATERIALS AND METHODS: CT and MRI findings of 78 patients (43 male, 35 female) aged 12-80 (mean 47.5) years surgically treated for lipomatous lesions of the head and neck region between January 1995 and June 2005 were retrospectively analysed and correlated with the histological results. RESULTS: On CT images, lipomas and fibrolipomas appeared as smooth (38/50 cases) or lobulated (12/50 cases) well-defined masses associated with moderate displacement of surrounding tissues; tumours had high signal intensity on MR T1-weighted images, with relative decreasing signal on T2-weighted images. Infiltrating lipomas appeared as expansile ill-defined masses with heterogeneous signal. Angiolipomas showed a characteristic contrast enhancement on both CT and MRI. In one case of sialolipoma, the lesion appeared markedly heterogeneous in signal. MR and CT images of Madelung's disease showed multiple symmetrical lipomatous masses involving the neck region. Intraosseous fatty lesions appeared as well-defined hypodense masses sometimes associated with cortical expansion and disruption. CONCLUSIONS: Both CT and MRI exams are useful for detecting lipomatous lesions. MRI, however, is more accurate in the evaluation of their extent and in the characterisation of uncommon lipomatous lesions of the head and neck, and intravenous administration of gadolinium better depicts the margins of the tumour and its vascularisation.