Transient ischemic attack and minor stroke as "surgeons affairs": a narrative review.

OBJECTIVE: The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications. MATERIALS AND METHODS: The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion. RESULTS: Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases. CONCLUSIONS: TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management.

DNA methylation of HOXA10 in eutopic and ectopic endometrium.

STUDY QUESTION: Does the methylation status of the promoter region of the HOXA10 gene differ in eutopic and ectopic endometrium? SUMMARY ANSWER: The eutopic endometrium in women with endometriosis is significantly more methylated when compared with controls. WHAT IS KNOWN ALREADY: Expression of the HOXA10 gene, which is important for successful implantation, is reduced in women affected by endometriosis. STUDY DESIGN, SIZE AND DURATION: A pilot study was carried out including 18 women admitted for surgery for endometriosis-related pain (cases) and 12 women admitted for surgery because of non-endometriotic disease (control). Sample collection and analysis were performed between November 2010 and July 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissue (eutopic and ectopic) underwent sodium bisulfite DNA modification, PCR amplification of two regions of the HOXA10 promoter and pyrosequencing analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The eutopic endometrium of women with endometriosis was significantly more methylated compared with endometrium from the control group (sequence 1: 8.68% in cases and 6.25% in the control group: P = 0.037, sequence 2: 11.89% in cases and 9.25% in the control group: P = 0.032). The eutopic endometrium was significantly more methylated than the ectopic tissue in patients with endometriosis (mean difference -3.6 sequence 1: P = 0.001 and -6.0 sequence 2: P = 0.0001). LIMITATIONS, REASONS FOR CAUTION: The study had a limited sample size and the fertility status of the majority of patients in our study was unknown. WIDER IMPLICATIONS OF THE FINDINGS: Our data regarding methylation state of the ectopic tissues contribute to a better etiopathologic understanding of endometriosis. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no conflicts of interests to declare.

Endometrial carcinoma in high-risk populations: is it time to consider a screening policy?

Endometrial carcinoma (EC) is the leading female genital tract malignancy in industrialized countries. It will become an important public health problem in the coming years in the USA and Europe, where its incidence is increasing, and next-generation interventions should include periodical screening in high-risk women. In this review, we discuss the importance to gynaecologists of detecting women at high risk and offering an adequate screening programme. Screening for EC is particularly challenging and there is currently no proven programme for the surveillance of women estimated to be at an increased risk of developing this form of cancer. The data in the literature, including this and previous issues of Cytopathology, and personal experience suggest that endometrial liquid-based cytology (LBC) might play an essential role in a screening policy for EC. LBC may enable practitioners to reduce age-adjusted mortality for women at high risk for EC.

[Tamoxifen, endometrial cancer risk and liquid based cytology. A paradigmatic case]. / Tamoxifene, rischio oncologico endometriale e citologia in fase liquida. Un caso clinico paradigmatico.

Long-term users of tamoxifen (TMX) are at increased risk for developing endometrial cancer. Early diagnosis is mainly based on transvaginal scan (TVS) and hysteroscopy with endometrial biopsy. Nevertheless, TVS does not provide a definitive diagnosis in most cases, particularly due to its high false-positive rate. In addition TMX related changes, such as "pseudocistic" pattern, affect endoscopic evaluation of the endometrium and biopsy sampling (in particular blind procedures) frequently yields insufficient tissue for diagnosis. The cause of the high inadequacy rate of endometrial biopsies in women on TMX might be related to the increase in endometrial fibrous component. The present case emphasizes the main difficulties in surveillance and early diagnosis of endometrial pathologies in TMX users. Liquid-based endometrial cytology played a determinant role in the diagnostic pathway of this patient. We believe it could be used solely or in association with TVS leading to many advantages in the surveillance of women receiving TMX.

Prospective evaluation of a prevention protocol for lymphedema following surgery for breast cancer.

Lymphedema is a common complication of axillary dissection and thus emphasis should be placed on prevention. Fifty-five women who had breast-conserving surgery or modified radical mastectomy for breast cancer with axillary dissection were randomly assigned to either the preventive protocol (PG) or control group (CG) and assessments were made preoperatively and at 1, 3, 6, 12 and 24 months postoperatively. Arm volume (VOL) was used as measurement of arm lymphedema. Clinically significant lymphedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. The preventive protocol for the PG women included preoperative upper limb lymphscintigraphy (LS), principles for lymphedema risk minimization, and early management of this condition when it was identified. Assessments at 2 years postoperatively were completed for 89% of the 55 women who were randomly assigned to either PG or CG. Of the 49 women with unilateral breast cancer surgery who were measured at 24 months, 10 (21%) were identified with secondary lymphedema using VOL with an incidence of 8% in PG women and 33% in CG women. These prophylactic strategies appear to reduce the development of secondary lymphedema and alter its progression in comparison to the CG women.

The role of lymphoscintigraphy in the diagnosis of lymphedema in Turner syndrome.

Lymphedema can be present in patients affected by Turner syndrome (TS) with the dorsum of the hands and feet most commonly affected. This lymphedema results from underdevelopment of the lymphatic system before birth, and it usually decreases during childhood. The aim of our study was to evaluate the role of lymphoscintigraphy as a diagnostic tool in patients with TS to assess possible impairments in the lymphatic system. Eighteen patients with TS were karyotyped to confirm diagnosis and were evaluated by lymphoscintigraphy. Lymphatic dysfunction was demonstrated in 15/18 patients. Lymphoscintigraphic studies showed: 1) lymphatic channels, 2) collateral lymphatic channels, 3) interrupted lymphatic structures, and 4) lymph nodes of the deep lymphatic system. Our data demonstrate that lymphoscintigraphy should be mandatory not only in patients affected by Turner syndrome with signs of lymphatic dysplasia but also in those with minimal or absent signs of lymphatic impairment in order to obtain a very early diagnosis and to provide substantial information for possible medical or surgical treatment.

Clinical utility of liquid-based cytology for the characterization and management of endometrial polyps in postmenopausal age.

The proper management of endometrial polyps still represents a clinical ongoing challenge, especially when they are asymptomatic and occasionally discovered. The aim of this study was to evaluate liquid-based endometrial cytology to manage endometrial polyps in postmenopausal age by its ability to exclude hidden premalignant and malignant changes within polyps. Three hundred fifty-nine consecutive postmenopausal patients who underwent hysteroscopic diagnosis of endometrial polyp over a 3-year period and who were scheduled for surgical removal within the three subsequent months were retrospectively evaluated. Histologic results after resection during operative hysteroscopy or during hysterectomy were compared with liquid-based cytology and endometrial biopsy obtained at the time of diagnostic hysteroscopy. Eight of 359 patients (2.2%) had malignant or premalignant polyps interpreted as benign finding at hysteroscopy. Unsatisfactory samples were higher for endometrial biopsy compared to liquid-based cytology in the whole series and in the subgroup of low-risk asymptomatic patients (P < 0.001). Endometrial biopsy and liquid-based cytology revealed a sensitivity of 62% and 87.5%, respectively and a 100% specificity. Considering the subgroup of low-risk asymptomatic patients, liquid-based cytology disclosed all the five pathologic lesions with a 100% sensitivity and specificity. In conclusion, liquid-based cytology proved to be a useful tool to establish the nature of endometrial polyps in postmenopausal patients. Complete removal of the lesion should be offered to all symptomatic patients and those with established risk factors for endometrial cancer. Conversely, a wait and see attitude should be considered in case of asymptomatic low-risk polyps with typical appearance on hysteroscopy and negative liquid-based cytology.

Occipital pilomyxoid astrocytoma in a 14-year-old girl--case report.

Pilomyxoid astrocytoma is a recently described tumor. Its most typical morphological characteristics are an angiocentric astrocytic proliferation embedded in a myxoid background. The behavior seems to be unfavorable due to the reported high rate of local recurrence. The earlier studies indicated that pilomyxoid astrocytoma typically affects young children and arises in the hypothalamic/chiasmatic region. We report a case of a 14-year-old patient with a 6-year history of absence seizure. Magnetic resonance imaging showed a right occipital lesion of approximately 3 cm in diameter. The patient underwent the surgical procedure with gross total excision. Histologically, the tumor was mainly composed of a monomorphous population of bipolar elongated piloid cells radially arranged around thin-walled blood vessels in a prominent myxoid background. There were focal hemorrhagic foci but no bona fide evidence of tumor necrosis or mitoses. Rosenthal fibers and eosinophilic granular bodies were not observed. The postoperative course was uneventful. No adjuvant therapy was administered. The patient is alive and well at 18-month follow-up. The case presented provides evidence that pilomyxoid astrocytoma can occur at a later age and can arise in regions different from hypothalamic/chiasmatic.

Tumor markers in ovarian carcinoma.

This review analyzes in 2 ways the prognostic value of markers found in ovarian carcinomas before chemotherapy. It is known that neoangiogenesis, cyclooxygenase activity, and host responsiveness to chemotherapy can be evaluated by means of specific molecules recognized as tumor markers. However, host response as well as tumor histotype, grade of differentiation, clinical characteristics, and histopathologic characteristics must also be taken into account when selecting a treatment. Analysis must therefore focus on the molecular basis of aggressive disease, on tumor peculiarity, on the efficacy of chemotherapy, and on the host's response to the tumor. Although treatment may be more aggressive in patients with unfavorable prognostic elements, it may be modulated according to the molecular and cellular biology of the tumor and the host's response. When the tumor's molecular characterization contributes to the choice of treatment, prognostic markers may turn into predictive markers.

Inducible cyclooxygenase (COX-2) in glioblastoma--clinical and immunohistochemical (COX-2-VEGF) correlations.

Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme responsible for the first step in the prostaglandin synthesis. COX-2 upregulation is demonstrated in different tumors. COX-2 products may modulate tumoral growth, apoptosis, metastasis, multidrug resistance and angiogenesis. Moreover, the antitumoral effect of the COX inhibitors has been documented. We studied the immunohistochemical expression and the prognostic value of COX-2 on 43 surgical specimens of glioblastoma-affected patients. Furthermore, we evaluated the correlation between the immunohistochemical expression of COX-2 and vascular endothelial growth factor (VEGF). Of the glioblastomas, 63% resulted as COX-2-positive. Median survival of the patients with COX-2-positive lesions was 10 months; median survival of the patients with COX-2 negative glioblastoma was 21 months (NS). All 4 patients who survived longer than 24 months had COX-2 negative lesions (p = 0.017). Concordance between COX-2 and VEGF was documented in 60% of the cases. Our findings show that glioblastoma can immunohistochemically express COX-2 and that its expression is unrelated with VEGF and significantly less frequent in the long survivors. Nevertheless, the absence of statistical correlation with survival time advises further studies on larger series to ascertain the concrete prognostic value of COX-2 in glioblastoma.

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

Oligodendrogliomas lacking O6-methylguanine-DNA-methyltransferase expression.

O6-Methylguanine-DNA-Methyltransferase (MGMT) is a DNA repair protein considered to be a chemosensitivity predictor. We evaluated the immunohistochemical MGMT expression in 28 consecutive oligodendroglial tumors (21 oligodendrogliomas, 5 mixed oligoastrocytomas, and 2 glioblastomas with prominent oligodendroglial features; 13 treated with CCNU) and compared it with that of 13 glioblastomas. Twenty-six (93%) oligodendroglial tumors were MGMT-negative, 2 (7%) were MGMT-positive. Twelve (92%) patients treated with CCNU had MGMT-negative lesions and their median survival was 73 months; 1 patient had an MGMT-positive oligodendroglioma and is alive at 28 months. Three (23%) glioblastomas were MGMT-negative and 10 (77%) MGMT-positive. The lower MGMT expression in oligodendroglial tumors compared to glioblastomas (P < 0.05), which have different chemosensitivity, suggests a possible role of MGMT in the determination of chemoresistance. Nevertheless, the heterogeneous outcome of our MGMT-negative oligodendroglial tumors treated with CCNU, indicates that MGMT expression alone is insufficient to predict the response to alkylating drugs, presumably because of the numerous mechanisms involved.

Pulmonary lymphangiectasia.

Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung and is characterized by pulmonary subpleural, interlobar, perivascular, and peribronchial lymphatic dilatation. Both frequency and etiology are unknown. PL presents at birth with severe respiratory distress, tachypnea, and cyanosis, with a very high mortality rate at or within a few hours of birth. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated to prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy present medical problems which are characteristic of chronic lung disease.

Diagnostic protocol for lymphoscintigraphy in newborns.

The purpose of this methods paper is to offer pediatricians and nuclear medicine physicians a diagnostic protocol for performing lymphoscintigraphy in newborns that may be useful for enhancing diagnosis and management of newborns with congenital lymphatic abnormalities. Indications for lymphoscintigraphy, choice of tracer, optimal dose, routes of administration, methods of data acquisition, timing, and interpretation of results for newborns are presented and discussed.

Systemic haemodynamics in renovascular hypertension: changes after revascularization with percutaneous transluminal angioplasty.

The systemic haemodynamic pattern and its changes after at least 6 months of successful percutaneous transluminal angioplasty (PTRA) was evaluated in a group of patients with renovascular hypertension (RVH). Fourteen patients, nine males and five females, aged 21 to 58 years, were studied; 12 had fibrodysplastic and two had atherosclerotic stenosing renal vascular lesions. Seven were cured and seven improved. Hypertension was characterized by increased plasma volume (PV) and total peripheral vascular resistance (TPR). Mean peripheral plasma renin activity (PRA) and 24-h urine aldosterone (UA) were elevated. However, the vasoconstriction did not appear to be related to the increased activity of the renin-angiotensin system. After at least 6 months of a successful PTRA, the fall in blood pressure (BP) was associated with a decrease in TPR; PV appeared normal, and PRA and UA became normal.

99mTc-HMPAO regional cerebral blood flow and quantitative electroencephalography in Alzheimer's disease: a correlative study.

UNLABELLED: In this study the neuropsychological status of patients with Alzheimer's disease (AD) was correlated with quantitative electroencephalography (qEEG) and regional cerebral blood flow (rCBF) both in the cortex and in deep gray matter structures. METHODS: Forty-three outpatients (mean age 72.4 +/- 7.5 y) with probable AD underwent 99mTc-hexamethyl propyleneamine oxime SPECT with a brain-dedicated gamma camera and qEEG (relative values) within 1 mo. Preliminary factorial analysis with promax rotation identified four qEEG bands (2-5.5, 6-7.5, 8-11.5 and 12-22.5 Hz, with no distinction as to topography) and six SPECT regions (the two thalami together, the two parietal cortices together, the right temporal cortex, the right hippocampus, the left hippocampus and the remaining cortical areas together) as the variables with highest statistical power. All these variables and the Mini-Mental Status Examination score (MMSE, a sensitive marker of neuropsychological deficit) were processed by a final factorial analysis and multivariate analysis of variance. RESULTS: Both the 2-5.5 Hz and the 8-11.5 Hz powers were correlated with the perfusion level in the parietal regions of interest (ROls) (P = 0.0009), whereas the 2-5.5 Hz power was correlated with the right hippocampal perfusion level (P = 0.007). The MMSE score was significantly correlated with the perfusion level, both in the right (P = 0.006) and in the left (P = 0.004) hippocampal ROls and in the parietal ROls (P = 0.01); moreover, it was correlated with both the 2-5.5 Hz (P = 0.0005) and the 8-11.5 Hz (P = 0.004) power. CONCLUSION: rCBF (bilateral parietal perfusion) and qEEG (especially the slowest frequencies, i.e., 2-5.5 Hz) are confirmed to be good descriptors of AD severity. It is especially noteworthy that bilateral hippocampal CBF was the perfusional index best correlated with the MMSE as well as being significantly correlated to qEEG. Hippocampal SPECT imaging appears to be a promising index to improve characterization of AD in respect to other forms of primary degenerative dementia and may be proposed as a marker for evaluating the effects of pharmacotherapy of AD at the neuronal level.

Inhibitory effect of luteinising hormone-releasing hormone analogues on human endometrial cancer in vitro.

We studied the effects of luteinising hormone-releasing hormone (LHRH) agonist leuproreline (1 microM for 96 h) and LHRH antagonist cetrorelix on the cell growth of primary cultures from nine human endometrial cancers using the sulphorhodamine colorimetric test. Histological examinations and reverse transcription and polymerase chain reaction amplification (RT-PCR) for LHRH receptors were also performed. The endometrial cancers examined had a medium to high degree of proliferative activity and a low degree of apoptotic power; furthermore, they expressed the LHRH receptor RNA variably, detectable in 71% of cases. The addition of leuproreline or cetrorelix to cell cultures inhibited growth in a statistically significant way compared to untreated control cells; nevertheless, the percentage of cell growth inhibition obtained was very variable. These data suggest that LHRH analogues can exert differential inhibitory effects on the growth of endometrial cancer, which seems to be independent of the expression of specific LHRH receptors.

Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma.

The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative cell-cycle regulator normally expressed in a number of adult tissues. This protein shares many structural and functional features with the product of the retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a fundamental role in growth control. The Rb2/p130 gene product associates with specific members of the E2F family and various cyclins, displaying a growth-suppressive activity specific for the G(0)/G(1) phases. It has been reported that Rb2/p130 is involved in the pathogenesis and progression of lung cancer and mesothelioma. We previously demonstrated for the first time that reduced immunohistochemical expression of Rb2/p130 was a strong independent predictor of poor outcome in endometrial cancer. The aim of the present study was to evaluate Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions to determine whether the protein plays a significant role in endometrial carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining in 102 specimens chosen to represent a spectrum of endometrial changes, including proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in proliferative endometrium and in hyperplasia without atypia, the mean percentage of stained nuclei being 66% and 60%, respectively, but was downregulated in secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of 38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale (negative v 1% to 50% v >50% positivity), endometrial cancer displayed significantly less staining than all other endometrial samples (P <.001). Poorly differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical hyperplasia showed a significantly lower immunoreactivity than either proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our findings of a progressive decrease in Rb2/p130 expression from hyperplastic endometrium through atypical hyperplasia to poorly differentiated carcinomas suggest the involvement of this negative cell-cycle regulator in endometrial carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically useful in the often difficult distinction between hyperplastic and atypical hyperplastic endometrium. HUM PATHOL 32:360-367.

Sugar residues content and distribution in atrophic and hyperplastic postmenopausal human endometrium: lectin histochemistry.

A lectin histochemical study was performed to investigate the glycoconjugate saccharidic moieties of the human postmenopausal endometrium (14 atrophic and 15 hyperplastic). For this purpose a battery of seven horseradish peroxidase-conjugated lectins (PNA, SBA, DBA, WGA, ConA, LTA and UEA I) was used. No differences in lectin binding between atrophic and hyperplastic endometria were observed. This investigation allowed us to provide a basic picture of the oligosaccharidic distribution in postmenopausal endometria. The data on the saccharidic distribution at the postmenopausal endometria showed a large amount of sugar residues at all the investigated sites, i.e. the lining and glandular epithelium, the stroma and the vessels (capillary and large vessels). Furthermore, at the endometrial lining epithelium, at the glands and at the wall of the blood vessels of some postmenopausal women the presence of alpha-L-fucosyl residues which bind via alpha (1-6) linkage to penultimate glucosaminyl residues and/or difucosylated oligosaccharides was demonstrated for the first time.