Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of ...healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s(-1)·mg(-1), P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g(-1)·min(-1), P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s(-1)·mg(-1), P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.
The purpose of this statement is to address the state of evidence on the routine use of pulse oximetry in newborns to detect critical congenital heart disease (CCHD).
A writing group appointed by the ...American Heart Association and the American Academy of Pediatrics reviewed the available literature addressing current detection methods for CCHD, burden of missed and/or delayed diagnosis of CCHD, rationale of oximetry screening, and clinical studies of oximetry in otherwise asymptomatic newborns. MEDLINE database searches from 1966 to 2008 were done for English-language papers using the following search terms: congenital heart disease, pulse oximetry, physical examination, murmur, echocardiography, fetal echocardiography, and newborn screening. The reference lists of identified papers were also searched. Published abstracts from major pediatric scientific meetings in 2006 to 2008 were also reviewed. The American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. In an analysis of pooled studies of oximetry assessment performed after 24 hours of life, the estimated sensitivity for detecting CCHD was 69.6%, and the positive predictive value was 47.0%; however, sensitivity varied dramatically among studies from 0% to 100%. False-positive screens that required further evaluation occurred in only 0.035% of infants screened after 24 hours.
Currently, CCHD is not detected in some newborns until after their hospital discharge, which results in significant morbidity and occasional mortality. Furthermore, routine pulse oximetry performed on asymptomatic newborns after 24 hours of life, but before hospital discharge, may detect CCHD. Routine pulse oximetry performed after 24 hours in hospitals that have on-site pediatric cardiovascular services incurs very low cost and risk of harm. Future studies in larger populations and across a broad range of newborn delivery systems are needed to determine whether this practice should become standard of care in the routine assessment of the neonate.
Genetic alterations in uterine myxoid leiomyosarcoma are unknown. We investigate the clinicopathologic features of 19 uterine tumors previously diagnosed as myxoid leiomyosarcomas in which tumoral ...RNA was subjected to targeted RNA sequencing. PLAG1, BCOR, BCORL1, HMGA2, and ALK break-apart fluorescence in situ hybridization (FISH) and BCOR, PLAG1, and ALK immunohistochemistry were performed in cases which failed or lacked fusions by sequencing. The diagnosis of myxoid leiomyosarcoma was confirmed in 15 cases after exclusion of 4 tumors with BCOR and ALK rearrangements. These 15 patients presented at a median age of 50 years with stage I (3), II (2), III (2), and IV (1) tumors, respectively; stage was unknown in 7 cases. Tumor size ranged from 10 to 24 cm. Matrix was myxoid in all tumors and also eosinophilic in 2. Cells were spindled, epithelioid, and both in 10, 2, and 3 tumors and showed mild, moderate, and severe nuclear atypia in 3, 8, and 4 tumors, respectively. Mitotic index ranged from <1 to 14/10 HPF, while tumor necrosis was present in 6 (40%). Novel TRPS1-PLAG1 or RAD51B-PLAG1 fusions were detected by sequencing in 4 tumors, 3 of which were also confirmed by FISH. Diffuse PLAG1 expression was seen in 7 tumors, including 4 with PLAG1 rearrangement. No morphologic differences were seen among PLAG1 fusion-positive and fusion-negative tumors. No PLAG1, HMGA2, ALK, BCOR, or BCORL1 rearrangements were detected by FISH in 11 tumors. On the basis of sequencing and FISH results, PLAG1 rearrangements resulting in PLAG1 expression underpin ~25% of myxoid leiomyosarcomas and may serve as a useful diagnostic biomarker. Immunohistochemistry, targeted RNA sequencing, and/or FISH may distinguish myxoid leiomyosarcoma from its morphologic mimics.
One hundred fifty yolk sac tumors (YSTs) of the ovary in patients from 1 to 61 (mean: 21.5) years of age are described; 75% of the patients were in the second and third decades and only 1 was above ...50 years of age. The clinical manifestations were typically related to a fast-growing adnexal mass; endocrine manifestations (hirsutism) were present in only 2 cases. The tumors were all unilateral and 70% were ≥15 cm; an associated dermoid cyst was present in 20 cases. The tumors were solid and cystic in 57% of the cases, 25% were multicystic, and 18% uniformly solid. The solid tissue was typically tan to pink or yellow and often friable with hemorrhage and necrosis; smaller solid neoplasms were sometime uniformly yellow. The most common histologic pattern was reticular composed of an irregular meshwork of spaces that was conspicuous in 68% of the neoplasms but present to at least a minor degree in all of them. That appearance almost always merged with small to large cysts that were prominent in about 40% of tumors. In 25% of the tumors, cysts sometimes associated with a cellular stroma (the polyvesicular pattern), were present but conspicuous in only half these cases. One third of the tumors had a labyrinthine pattern, 22% glands, and 6% a festoon pattern. Papillae with a central blood vessel (Schiller-Duval bodies) were seen in one-third of the tumors but were numerous in only 5% of them. Nonspecific appearing papillae were seen in 10% of the tumors. A solid growth of cells with pale cytoplasm was seen in one-third of the tumors but was conspicuous in only half of that subset. The solid appearance was typically reminiscent of that of dysgerminoma, but lacked the septa and lymphocytic infiltrate of that neoplasm. Nine tumors had a component of cells with scant cytoplasm resulting in a blastema-like appearance and 3 had cells with abundant clear cytoplasm. Cords and clusters of cells were common but did not dominate the microscopic appearance. The stroma typically had a nonspecific collagenous to edematous appearance. Stromal luteinization was seen in 12 tumors; in 5 this was likely due to the patient being pregnant. Two tumors had minor foci of cells that resembled hepatocytes. Hyaline bodies were seen in most of the tumors and were often conspicuous. The neoplastic cells typically had modest amounts of lightly staining cytoplasm and only mild nuclear pleomorphism. Cells lining cysts were often flattened sometimes resulting in a deceptively innocuous appearance. Many of the tumors (mostly consultation cases), caused diagnostic difficulty; tumors in the differential diagnosis included clear cell carcinoma, embryonal carcinoma, Sertoli-Leydig cell tumor, and juvenile granulosa cell tumor. The patient age and marked elevation of the serum alpha-fetoprotein level (if measured) is helpful in many of these considerations. The overtly malignant gross appearance of most YSTs contrasts with certain other tumors in the differential and the association of some YSTs with dermoid cyst and many clear cell carcinomas with endometriosis may be helpful. The vast majority of ovarian YSTs are dominated microscopically by merging of reticular and cystic patterns which, although focally mimicked by other neoplasms, are in general characteristic, and distinctive features of other neoplasms are absent. Immunohistochemistry, particularly for alpha-fetoprotein and glypican 3, and lack of staining for various markers of other neoplasms is helpful but overlap exists and these results must be considered in the context of the overall clinical, gross, and microscopic features. YSTs dominated by hepatoid and glandular features are rare and their categorization as YSTs should be done cautiously if thoroughly sampled tumors show no evidence of classic features of YST emphasized herein and first elaborated by the Danish investigator Gunnar Teilum whose seminal observations have stood the test of time.
Abstract The relative frequency of ovarian tumors and tumor-like lesions that occur in young females (defined in this article as up to 30 years of age) differs considerably from that seen in older ...patients. The spectrum of lesions encountered is reviewed, with emphasis on those disproportionately seen in younger patients, particularly primitive germ cell tumors, certain tumors in the sex cord-stromal family, the distinctive tumor known as small cell carcinoma of hypercalcemic type, and selected tumor-like lesions. Comments are made initially on the relative frequency of the various well-known categories of ovarian neoplasia in the first three decades, compared to females overall, and differences within the first three decades are noted. Some of the more noteworthy of these include the occurrence of follicular cysts in neonates due to in-utero maternal stimulation, and the often large size of these lesions, with sometimes dramatic clinical manifestations; the relative rarity of the commonest germ cell tumor of the ovary, the dermoid cyst, in the very early years of life; the peak incidence of all primitive germ cell tumors in the mid to late teens and early 20s; the peak of small cell carcinoma of hypercalcemic type in the early 20s; the preponderance for the juvenile granulosa cell tumor to occur in the first two decades and for one distinctive form of Sertoli–Leydig cell tumor, the retiform variant, to peak at about 15 years of age; the occasional finding of mucinous cystic tumors, usually benign, in the teenage years, and their greater frequency than other surface epithelial neoplasms; a gradual increase in frequency of all types of surface epithelial neoplasia, but particularly mucinous tumors and serous tumors as patients move through the 20s; and the rarity of metastatic neoplasia in the first three decades in general, but with occasional dramatic examples such as some Krukenberg tumors being seen in these years, as may some of the distinctive tumors of the young such as neuroblastoma. Consideration of the gross and microscopic features, and differential diagnosis, of individual neoplasms follows the introductory remarks and emphasizes the importance of gross pathology. An example of the latter is the marked difference in most cases between a dermoid cyst and an immature teratoma, the former being dominantly cystic and the latter dominantly solid, and the latter on average twice as large as the former. Caution should be exercised in entertaining a diagnosis of immature teratoma if a lesion is grossly a typical dermoid cyst. The treacherous shared gross characteristics and age distribution of the dysgerminoma and small cell carcinoma of hypercalcemic type are noted. The rarity of monodermal teratomas and malignant neoplasms such as squamous cell carcinoma arising in dermoid cysts in the first three decades is noted. The distinctive features of two recently described stromal neoplasms, microcystic stromal tumor and luteinized thecomas of the type associated with sclerosing peritonitis, are emphasized as is the varied differential diagnosis of the juvenile granulosa cell tumor and Sertoli–Leydig cell tumor. Sections on ovarian tumors and tumor-like lesions in pregnant patients and tumor-like lesions overall conclude the article.
One-hundred fourty pure dysgerminomas were evaluated with particular focus on the microscopic features as seen in 125 cases with available slides. The patients ranged from 8 to 59 years of age (mean, ...24.1 y). The tumors, bilateral in 4% of the cases and with a mean tumor diameter of 13 cm, were typically soft, lobulated, homogeneous, and creamy white to tan to yellow but necrosis was found in 13%, hemorrhage in 20%, and focal cystic change in 15%. On microscopic examination, the patterns and other notable features encountered, including their frequency, were as follows: an alveolar pattern resulting from delicate fibrovascular septa (51%), diffuse (33%), macronodular (14%), insular (26%), cords (28%), solid tubular (17%), microspaces (sometimes simulating glands) (12%), follicle-like spaces (5%), prominent fibrous bands (65%), stromal edema (56%), stromal luteinization (9%), granulomatous infiltrate (46%), lymphocytic infiltrate (100%), Langhans cell type giant cells (35%), syncytiotrophoblast giant cells (6%), prominent population of cells with pale to clear cytoplasm (73%), cells with amphophilic to eosinophilic cytoplasm (53%) and vacuolated occasionally signet ring-like cells (7%). Various constellations of the above findings often resulted in an appearance different from that usually portrayed in the literature and certain tumors of very different nature being in the differential such as undifferentiated carcinoma not otherwise specified, small cell carcinoma of hypercalcemic type, and malignant lymphoma. The correct diagnosis can be arrived at by considering the usual relative youth of the patient, often rather characteristic gross features, and most crucially careful attention to the microscopic features and awareness of variant morphologic findings. Those that are particularly problematic based on this study are diffuse growth with inconspicuous fibrovascular septa, macronodules, cords, solid tubular formations, spaces ranging from small to large, and mimicking glands or follicles, prominent fibrous to edematous stroma, and cells with amphophilic to eosinophilic cytoplasm. According to the degree of difficulty and confidence of the interpreter, well-known immunohistochemical features of dysgerminoma, which largely differ from those of other neoplasms in the differential, will aid if felt indicated.
Uncommon gynecologic cancers del Carmen, Marcela G; del Carmen, Marcela G; Schorge, John O ...
2014., 2014, 20150101, 2014-11-11, 2014-11-10
eBook
Rare gynecological cancers kill all too commonly Gynecological cancer is a frightening prospect for women. It is terrifying also for physicians who need, but often can't find, guidance on how to ...investigate and appropriately treat the tumors. Rare cancers provide greater challenges as information can be harder to find and more difficult to verify. Rare Gynecologic Cancers: Diagnosis and Management brings together all you need to know on these life-threatening diseases. Straightforward summaries of pathophysiologic processes lead to the investigations that will improve your diagnostic accuracy. This provides the basis for you to identify effective treatment strategies for your patients. Written by a world-leading team of Editors and Authors and covering cancers of the • Ovaries • Uterus • Vulva • Vagina • Cervix Rare Gynecologic Cancers: Diagnosis and Management will guide you to the best life-saving treatment for your patients.
Neuroendocrine neoplasms (NENs) of the cervix are rare aggressive tumors associated with poor prognosis and only limited treatment options. Although there is some literature on molecular ...underpinnings of cervical small cell neuroendocrine carcinomas (SCNECs), detailed morphologic and associated molecular characteristics of cervical NENs remains to be elucidated. Herein, 14 NENs (SCNEC: 6, large cell neuroendocrine carcinoma LCNEC: 6, neuroendocrine tumor NET: 2), including 5 admixed with human papillomavirus (HPV)-associated adenocarcinoma (carcinoma admixed with neuroendocrine carcinoma) were analyzed. All except 3 SCNECs were HPV16/18 positive. TP53 (3) and/or RB1 (4) alterations (3 concurrent) were only seen in SCNECs (4/6) and were enriched in the HPV16/18-negative tumors. The other most common molecular changes in neuroendocrine carcinomas (NECs) overlapping with those reported in the literature for cervical carcinomas involved PI3K/MAPK pathway (4) and MYC (4) and were seen in both SCNECs and LCNECs. In contrast, the 2 NETs lacked any significant alterations. Two LCNECs admixed with adenocarcinoma had enough material to sequence separately each component. In both pathogenic alterations were shared between the 2 components, including ERBB2 amplification in one and an MSH6 mutation with MYC amplification in the other. Overall, these findings suggest that cervical HPV-associated NETs are genomically silent and high-grade NECs (regardless of small or large cell morphology) share molecular pathways with common cervical carcinomas as it has been reported in the endometrium and are different from NECs at other sites. Molecular analysis of these highly malignant neoplasms might inform the clinical management for potential therapeutic targets.
Exposure to ionizing radiation remains a hazard for patients and healthcare providers. We evaluated the utility of an artificial intelligence (AI)-enabled fluoroscopy system to minimize radiation ...exposure during image-guided endoscopic procedures.
We conducted a prospective study of 100 consecutive patients who underwent fluoroscopy-guided endoscopic procedures. Patients underwent interventions using either conventional or AI-equipped fluoroscopy system that uses ultrafast collimation to limit radiation exposure to the region of interest. The main outcome measure was to compare radiation exposure with patients, which was measured by dose area product. Secondary outcome was radiation scatter to endoscopy personnel measured using dosimeter.
Of 100 patients who underwent procedures using traditional (n = 50) or AI-enabled (n = 50) fluoroscopy systems, there was no significant difference in demographics, body mass index, procedural type, and procedural or fluoroscopy time between the conventional and the AI-enabled fluoroscopy systems. Radiation exposure to patients was lower (median dose area product 2,178 vs 5,708 mGym, P = 0.001) and scatter effect to endoscopy personnel was less (total deep dose equivalent 0.28 vs 0.69 mSv; difference of 59.4%) for AI-enabled fluoroscopy as compared to conventional system. On multivariate linear regression analysis, after adjusting for patient characteristics, procedural/fluoroscopy duration, and type of fluoroscopy system, only AI-equipped fluoroscopy system (coefficient 3,331.9 95% confidence interval: 1,926.8-4,737.1, P < 0.001) and fluoroscopy duration (coefficient 813.2 95% confidence interval: 640.5-985.9, P < 0.001) were associated with radiation exposure.
The AI-enabled fluoroscopy system significantly reduces radiation exposure to patients and scatter effect to endoscopy personnel (see Graphical abstract, Supplementary Digital Content, http://links.lww.com/AJG/B461).
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