Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature.

Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFß and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors' proliferative index (Ki67) increased from 5-6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

Effect of radiation dose reduction on image quality in adult head CT with noise-suppressing reconstruction system with a 256 slice MDCT.

The purpose of our study was to investigate the effect of iterative reconstruction (IR) as a dose reduction system on the image quality (IQ) of the adult head computed tomography (CT) at various low-dose levels, and to identify ways of setting the amount of dose reduction. We performed two noncontrast low-dose (LD) adult head CT protocols modified by lowering the tube current with IR which were decided in the light of a group of phantom studies. Two groups of patients, each 100 underwent noncontrast head CT with LD-I and LD-II, respectively. These groups were compared with 100 consecutive standard dose (STD) adult head CT protocol in terms of quantitative and qualitative IQ. The signal-to-noise ratio (SNR) of the white matter (WM) and gray matter (GM) and contrast-to-noise ratio (CNR) values in the LD groups were higher than the STD group. The differences were statistically significant. When the STD and the LD groups were compared qualitatively, no significant differences were found in overall quality. By selecting the appropriate level of IR 34%, radiation dose reduction in adult head CT can be achieved without compromising IQ.

Compression of the Celiac Artery by the Median Arcuate Ligament: Multidetector Computed Tomography Findings and Characteristics.

PURPOSE: The prevalence of the celiac artery stenosis caused by median arcuate ligament (MAL) compression and its multidetector computed tomography (MDCT) characteristics were evaluated in patients who underwent abdominal MDCT procedures, retrospectively. METHODS: Totally 1121 patients who had abdominal MDCT with arterial phase or MDCT angiography of the abdominal aorta for various indications were analyzed for celiac artery compression by the MAL. RESULTS: Fifty (ie, 4.6%) patients showed typical MDCT features of MAL compression. Focal narrowing of the proximal celiac artery, a characteristic hooked appearance of the narrowed segment without calcification and atherosclerotic changes were diagnostic. Poststenotic dilatation was detected in 22 (44%) patients with MAL compression. The ratio of the stenosis of the celiac artery was between 35%-50% in 15 patients and 51%-80% in 35 patients. The gastroduodenal artery diameter of these patients was not significantly different from the asymptomatic control group. CONCLUSION: MALS is an uncommon entity but it should be kept in mind in the presence of unexplained gastrointestinal symptoms. MDCT is a minimally invasive and plays a dominant role in the diagnosis of MAL compression especially with reformatted and 3-D reconstructed images.

Our Experience with MR Imaging of Perianal Fistulas.

Magnetic resonance imaging (MRI) depicts infectious foci in the perianal region better than any other imaging modality. MRI allows definition of the fistula, associated abscess formation and its secondary extensions. Accurate information is necessary for surgical treatment and to obtain a decrease in the incidence of recurrence and complications. Radiologists should be familiar with anatomical and pathological findings of perianal fistulas and classify them using the MRI - based grading system. The purpose of this article was to provide an overview for evaluation of perianal fistulas, examples of various fistula types and their classification.

Unusual left atrial mass: inverted left atrial appendage caused by massive pericardial effusion.

Left atrial appendage inversion is a very rare cause of left atrial mass that usually occur after cardiac surgery. Its echocardiographic appearance often misleads clinicians to the diagnosis of thrombus or cardiac neoplasms. Unfortunately, misdiagnosed patients often undergo unnecessary anticoagulation or surgical treatment. We are presenting a case of left atrial appendage inversion caused by massive pericardial effusion in a patient with no previous history of cardiac surgery together with demonstrative images of transesophageal echocardiography and magnetic resonance imaging.

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case.

BACKGROUND: Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients' serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community. METHODS: MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder. RESULTS: MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment. CONCLUSIONS: IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.

A pedunculated left ventricular hemangioma initially misdiagnosed as thrombus in a woman with atypical chest pain.

The incidence of cardiac masses increased as echocardiography is becoming increasingly popular. Benign tumors of the heart constitute about 72% of all primary cardiac neoplasms and hemangioma accounts for 5-10% of benign cardiac tumors. Cardiac hemangiomas are generally asymptomatic and diagnosed incidentally during echocardiography or magnetic resonance imaging (MRI). We reported a 52-year-old woman presented with atypical chest pain and exertional dyspnea. The echocardiographic examination revealed a hyperechoic round mass in the left ventricle. With an initial diagnosis of left ventricular thrombus, the patient underwent cardiac MRI. The mass was found compatible with cardiac hemangioma. It was removed surgically and histopathologic evaluation identified a cardiac hemangioma. As reports of cardiac hemangioma are extremely rare and cardiac masses are mostly thought to be thrombi or myxomas (being the most common primary cardiac tumor), such hemangioma cases warrant attention as possibility of hemangioma should also be kept in mind.

Large apical thrombus in a patient with persistent heart failure and hypereosinophilia: Löffler endocarditis.

Idiopathic hypereosinophilic syndrome is an uncommon leukoproliferative systemic disorder characterized by the overproduction of eosinophils and poor prognosis. A major source of morbidity and mortality of this syndrome is the associated cardiac involvement represented by endocardial thickening and mural thrombi. We report a 64-year-old woman with persistent symptoms of heart failure despite standard medical therapy. Echocardiography revealed reduced left ventricular filling due to a large apical mass; an abnormal diastolic filling pattern was also noticed. Complete blood count revealed remarkable hypereosinophilia. Cardiac magnetic resonance imaging demonstrated an apical thrombus and intense linear enhancement of the endocardium, which were compatible with Löffler endocarditis. Medical therapy, including corticosteroids and anticoagulation, was initiated promptly. The symptoms improved as the peripheral hypereosinophilia resolved in 15 days. The patient was asymptomatic at the 1-year follow-up visit with complete regression of the apical thrombus and no evidence of restrictive cardiomyopathy. We report this case to draw attention to this particularly rare condition with poor prognosis since quick and accurate diagnosis and prompt initiation of therapy may improve symptoms and survival.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.

Histogram Analysis Parameters Apparent Diffusion Coefficient for Distinguishing High and Low-Grade Meningiomas: A Multicenter Study.

Low grade meningiomas have better prognosis than high grade meningiomas. The aim of this study was to measure apparent diffusion coefficient (ADC) histogram analysis parameters in different meningiomas in a large multicenter sample and to analyze the possibility of several parameters for predicting tumor grade and proliferation potential. Overall, 148 meningiomas from 7 institutions were evaluated in this retrospective study. Grade 1 lesions were diagnosed in 101 (68.2%) cases, grade 2 in 41 (27.7%) patients, and grade 3 in 6 (4.1%) patients. All tumors were investigated by MRI (1.5 T scanner) by using diffusion weighted imaging (b values of 0 and 1000 s/mm2). For every lesion, the following parameters were calculated: mean ADC, maximum ADC, minimum ADC, median ADC, mode ADC, ADC percentiles P10, P25, P75, P90, kurtosis, skewness, and entropy. The comparison of ADC values was performed by Mann-Whitney-U test. Correlation between different ADC parameters and KI 67 was calculated by Spearman's rank correlation coefficient. Grade 2/3 meningiomas showed statistically significant lower ADC histogram analysis parameters in comparison to grade 1 tumors, especially ADC median. A threshold value of 0.82 for ADC median to predict tumor grade was estimated (sensitivity = 82.2%, specificity = 63.8%, accuracy = 76.4%, positive and negative predictive values were 83% and 62.5%, respectively). All ADC parameters except maximum ADC showed weak significant correlations with KI 67, especially ADC P25 (P = -.340, P = .0001).

Brachial artery thrombosis mimicking De Quervain's syndrome: a case report.

Upper limb occlusions are rare and the clinical presentation may vary depending on the affected arteries. A detailed history and physical examination may reveal possible causes and can facilitate the differential diagnosis. It can be misdiagnosed as musculoskeletal diseases due to similar clinical manifestations. In this report, we present a case with wrist pain mimicking de Quervain's syndrome diagnosed as subacute brachial artery thrombosis due to factor II gene mutation. In conclusion, physicians should be cautious to avoid unnecessary delay in the diagnosis of thrombosis in young patients.

Whorling-sclerosing meningioma. A review on the histological features of a rare tumor including an illustrative case.

Whorling-Sclerosing variant of meningioma (WSM) is a very rare variant of meningioma and only 28 cases were previously reported in the English medical literature. The term "whorling" describes different morphological features including psammoma bodies formed by precipitated calcium or by layered whorling sheets of tumor cells in meningothelial meningiomas. In WSM, the sclerosing structures are formed by typical paucicellular or acellular collagen whorls which form the majority of tumor volume. Hence, diagnosis of these tumors is based more often on morphological and histochemical features rather than on immunohistochemical findings. WSMs often contain cells with both fibroblast-like spindle cell morphology predominantly immunopositive for vimentin and meningoepithelial cells immnunopositive for EMA. The range of their Ki-67 indices differs between 0 and 4 percent. These tumors show no focal pleomorphism, necrosis and high mitotic activity. In some WSMs, entrapped GFAP immunopositive astrocytes may be seen during invasion of the adjacent neural parenchyma. Brain invasion by WSMs may give rise to erroneous diagnoses, i.e. malignant (Grade-3) meningioma, meningiosarcoma, ganglioglioma and even astrocytoma, leading detrimental overtreatment. However; hitherto, no WSM was reported exerting any aggressive behavior. Besides reviewing the literature, we also report a new WSM with abundant uncalcified paucicellular collagen whorls forming aggregates of nodules. Unlike to previous reports, this tumor was costained with p53 and progesterone receptor. The tumor showed no morphological malignancy characteristics, e.g. cellular atypia, prominent nucleoli, hypercellularity, micronecrosis/geographical necrosis, sheeting and small cells. This rare meningioma variant should be kept in mind among differential diagnoses to avoid overtreatment that might endanger patients' outcome.

Management of Failed Cranioplasty.

AIM: Failed cranioplasty attempts may lead to numerous complications in a broad spectrum including cosmetic problems, infection, neurological deterioration and even death. Selection of the most appropriate surgical technique for second and further surgical attempts for these patients still remains a debate. We aimed to share our experience and technical pitfalls on management of failed cranioplasty, particularly for patients with large cranial defects. MATERIAL AND METHODS: A retrospective data analysis of cranioplasty cases in our series was performed including the time period between 2002 and 2012. Patients required recurrent cranioplasty were analyzed in detail. RESULTS: Totally, 101 patients underwent cranioplasty for bony defect. Of 101 patients, eleven required a revision surgery due to infection or spontaneous resorption of the bone flap. All patients underwent revision cranioplasty with pre-surgical plaster cast mold technique modified from previous studies and/or tissue expansion technique. Polymethyl-metacrylate (PMMA) was used as substitute for reconstructions. Mean follow-up was 36 months. Two out of eleven cases (18.1%) developed major complications, which led to further revision. At the end, a satisfactory reconstruction was achieved for all patients. CONCLUSION: Our modified molded plaster cast technique is a safe and cost-effective approach for the revision of failed cranioplasty. We believe that the tissue expanding techniques have also great contribution to achieve successful results.

Portal biliopathy, magnetic resonance imaging and magnetic resonance cholangiopancreatography findings: a case series.

Portal biliopathy (PB) is a rare disorder, characterized by biliary ductal and gallbladder wall abnormalities seen in patients with portal hypertension. It most commonly occurs due to idiopathic extrahepatic portal vein obstruction (EHPVO). The abnormalities consist mainly of bile duct compression, stenoses, fibrotic strictures and dilation of both extrahepatic and intrahepatic bile ducts, as well as gallbladder varices. PB may mimic cholangiocarcinoma, sclerosing cholangitis, or choledocholithiasis. Misdiagnosis can be avoided using appropriate imaging modalities to prevent complications. We present the magnetic resonance imaging (MRI) and magnetic resonance cholangiography (MRCP) features of three patients with PB.

Meandering right pulmonary vein associated with retrocaval ureter and vertebral fusion anomalies.

We present multimodality imaging of a meandering right pulmonary vein in a 29-year-old female patient. It was associated with right retrocaval ureter causing hydronephrosis and stone formation, vertebral fusion anomalies and corrected cardiac anomalies (patent ductus arteriosus and ventricular septal defect). To the best of our knowledge, only a few meandering right pulmonary vein have been presented in the literature until now and this is the first reported case that is associated with retrocaval ureter and vertebral fusion anomalies.

Relation of apparent diffusion coefficient with Ki-67 proliferation index in meningiomas.

OBJECTIVE: The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and apparent diffusion coefficient (ADC) values of low-grade and atypical/anaplastic (high-grade) meningiomas. METHODS: Pre-operative diffusion-weighted imaging and histopathological evaluation of 44 patients with meningiomas were performed retrospectively. Regions of interest (ROIs) were manually drawn on the ADC images. In total six ROI measurements were taken in three consecutive slices, and the average of the mean ADC value was used. The relationship between the ADC and Ki-67 values was investigated, and the ADC values of the low-grade and high-grade meningiomas were compared. RESULTS: 31 (70%) patients had low-grade the meningiomas. 10 (23%) patients had atypical and 3 (7%) had anaplastic meningiomas. ADC values of the low-grade and high-grade meningiomas were 0.81 ± 0.12 × 10(-3) and 0.66 ± 0.08 × 10(-3) mm(2) s(-1), respectively. Ki-67 proliferation indexes were 2.19% ± 1.14% for low-grade and 11.20% ± 9.80% for high-grade meningiomas. A statistically significant negative correlation between Ki-67 proliferation index and ADC values of the low-grade and high-grade meningiomas was detected (r(2) = 0.326, p < 0.001). High-grade meningiomas had lower ADC values than that of low-grade meningiomas. There was statistically significant difference between the ADC values of the low-grade and high-grade meningiomas (p < 0.001). CONCLUSION: Our data provide an inverse correlation between the ADC and Ki-67 proliferation index values of meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning. ADVANCES IN KNOWLEDGE: The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and ADC values of low-grade and atypical/anaplastic (high-grade) meningiomas. In addition, we compared the ADC and Ki-67 proliferative index values of the low-grade and atypical/anaplastic (high-grade) meningiomas. We concluded that there was an inverse correlation between the ADC and Ki-67 proliferation index values in meningiomas, and we have found statistically significant difference between the ADC values of the low-grade and high-grade meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning.

Problems with the Median Arcuate Ligament Should Be Recognized before Surgery; Its Importance in Pancreaticoduodenectomy.

BACKGROUND: Celiac artery stenosis (CAS) is a not a rare finding in the general population. The median arcuate ligament (MAL) is a fibrous arch that unites the diaphragmatic crura on either side of the aortic hiatus and, while it normally passes cranial to the origin of the celiac truncus, a low-lying ligament may lead to compression of the celiac artery and is the one of the major causes of CAS. CASE REPORT: In this paper, we present a patient with a mass in the gastric bulbus who was diagnosed with celiac artery stenosis during the pancreaticoduodenectomy (PD). MAL was the cause of the celiac artery stenosis, determined based on the findings of preoperative computed tomography (CT). CONCLUSION: Although CAS is usually asymptomatic due to the collateral blood supply, it may be associated with potentially disastrous results due to ischemia of the upper abdominal organs as a result of disruption of the collateral pathways. It is especially important to recognize the presence of CAS and its etiology before interventional procedures. With the increasing use of multidetector computed tomography (MDCT), it becomes essential for radiologists to be aware of this entity and the cross-sectional findings.

Relationship of intraoperative ultrasound characteristics with pathological grades and Ki-67 proliferation index in intracranial gliomas.

OBJECTIVE: The purpose of the present study was to investigate the relationship between the intraoperative ultrasonographic appearances and the histopathological characteristics of glial tumors using the pathological grading system and the Ki-67 proliferation index. MATERIALS AND METHODS: Patients with glial tumors who underwent surgery with the aid of intraoperative ultrasonography (IOUS) between September 2013 and August 2014 were included in the study. The lesions' IOUS characteristics were analyzed and compared with the results of surgical histopathological characteristics. Lesions were classified as low-grade gliomas (grade I-II, LGG) and high-grade gliomas (grade III-IV, HGG). The glioblastoma multiforme (grade IV, GBM) group was classified according to the Ki-67 values for further evaluation. The Chi square test (Fisher's exact test) was used for comparing the ultrasonographic characteristics of the low-grade and high-grade gliomas; HGG with different Ki-proliferation indexes. A value of P < 0.05 was considered statistically significant. RESULTS: A total of 41 patients were included. The histopathological findings revealed 15 LGG and 26 HGG. Twenty of the 26 HGG were GBM. Differences were found between the intraoperative ultrasonographic characteristics of the low-grade and high-grade glial tumors. The majority of LGGs were mildly hyperechoic and homogeneous, with distinct margins and a regular contour. HGGs were mostly highly hyperechoic, with indistinct margins, irregular contours, and a heterogeneous internal texture. Surrounding edema was seen more often in HGGs. The differences in the echogenicity of the solid parts, the internal echo patterns, margins, contours, and peripheral edema (P < 0.05) were statistically significant, but the difference in the presence of cysts (P > 0.05) was not significant. In the GBM group, all of the lesions with distinct margins and regular contours had Ki-67 values ≤15 %. We compared the intraoperative ultrasonographic characteristics of the Ki-67 > 15 % group with those of the Ki-67 ≤ 15 % group for statistical significance. The difference between the echogenicity of the solid parts, margins, and contours was statistically significant between the groups (P < 0.05). The difference in the internal echo pattern, presence of cyst, and peripheral edema was insignificant (P > 0.05). CONCLUSIONS: IOUS is a very useful imaging technique not only in defining the borders but also in characterizing the tumoral tissue. The IOUS characteristics of the glial tumors were a valuable tool in differentiating the grades of the glial tumors and might have a relationship with the Ki-67 proliferation index. We think this theory requires further investigation in more detailed comparative studies with larger numbers of patients.

Focal megalencephaly: intraoperative ultrasound imaging in epilepsy surgery.

Hemimegalencephaly is a rare neuronal migration disorder that can be defined as abnormal neural and glial proliferation localized to all or part of a cerebral hemisphere. Most patients demonstrate intractable epilepsy, with early onset before 1 year of age. Surgical resection is one of the treatment options. In recent years, many advanced intraoperative techniques have been used for brain surgery for various pathologies. Intraoperative ultrasonography is a time-saving and noninvasive method for intraoperative imaging. In this report, we present the use of intraoperative ultrasonography in a patient with focal megalencephaly as an anatomical navigation with the functional navigation system, electrocorticography. In this report, we present the use of intraoperative ultrasonography in a patient with focal megalencephaly as an anatomical navigation with the functional navigation system, electrocorticography.