Synopsis Of Pathology (2013)

Hematopathology has been at the forefront in the adoption of newly available molecular techniques, and indeed the current WHO classification of hematolymphoid neoplasms has long since evolved from a morphologic classification to a classification that integrates clinical, morphologic, immunophenotypical, and molecular features in the definition of entities (37, 38).

Synopsis of Pathology (2013)

ABSTRACT: This Committee Opinion provides guidance on the current uses of hysteroscopy in the office and the operating room for the diagnosis and treatment of intrauterine pathology and the potential associated complications. General considerations for the use of diagnostic and operative hysteroscopy include managing distending media, timing for optimal visualization, and cervical preparations. In premenopausal women with regular menstrual cycles, the optimal timing for diagnostic hysteroscopy is during the follicular phase of the menstrual cycle after menstruation. Pregnancy should be reasonably excluded before performing hysteroscopy. There is insufficient evidence to recommend routine cervical ripening before diagnostic or operative hysteroscopy, but it may be considered for those patients at higher risk of cervical stenosis or increased pain with the surgical procedure. In randomized trials, patients reported a preference for office-based hysteroscopy, and office-based procedures are associated with higher patient satisfaction and faster recovery when compared with hospital-based operative hysteroscopy. Other potential benefits of office hysteroscopy include patient and physician convenience, avoidance of general anesthesia, less patient anxiety related to familiarity with the office setting, cost effectiveness, and more efficient use of the operating room for more complex hysteroscopic cases. Appropriate patient selection for office-based hysteroscopic procedures for women with known uterine pathology relies on thorough knowledge and understanding of the target pathology, size of the lesion, depth of penetration of the lesion, patient willingness to undergo an office-based procedure, physician skills and expertise, assessment of patient comorbidities, and availability of proper equipment and patient support. Both the American College of Obstetricians and Gynecologists (ACOG) and the American Association of Gynecologic Laparoscopists (AAGL) agree that vaginoscopy may be considered when performing office hysteroscopy because studies have shown that it can significantly reduce procedural pain with similar efficacy. The office hysteroscopy analgesia regimens commonly described in the literature include a single agent or a combination of multiple agents, including a topical anesthetic, a nonsteroidal antiinflammatory drug, acetaminophen, a benzodiazepine, an opiate, and an intracervical or paracervical block, or both. Based on the currently available evidence, there is no clinically significant difference in safety or effectiveness of these regimens for pain management when compared to each other or placebo. Patient safety and comfort must be prioritized when performing office hysteroscopic procedures. Patients have the right to expect the same level of patient safety as is present in the hospital or ambulatory surgery setting.

The American College of Obstetricians and Gynecologists and the American Association of Gynecologic Laparoscopists (AAGL) make the following conclusions and recommendations regarding the use of hysteroscopy for the diagnosis and treatment of intrauterine pathology:In premenopausal women with regular menstrual cycles, the optimal timing for diagnostic hysteroscopy is during the follicular phase of the menstrual cycle after menstruation. Pregnancy should be reasonably excluded before performing hysteroscopy.

Appropriate patient selection for office-based hysteroscopic procedures for women with known uterine pathology relies on thorough knowledge and understanding of the target pathology, size of the lesion, depth of penetration of the lesion, patient willingness to undergo an office-based procedure, physician skills and expertise, assessment of patient comorbidities, and availability of proper equipment and patient support.

This Committee Opinion provides guidance on the current uses of hysteroscopy in the office and the operating room for the diagnosis and treatment of intrauterine pathology and the potential associated complications.

Traditionally, targeted removal of intrauterine pathology using a monopolar or bipolar wire loop resectoscope required transcervical specimen removal of tissue fragments, often involving repetitive introduction of surgical instruments with potential for increased trauma to the cervix and uterus. Newer hysteroscopic tissue removal systems have emerged, allowing for the removal of lesions by simultaneous tissue resection and specimen extraction. Potential advantages of hysteroscopic tissue removal systems are shorter operative time and higher likelihood of complete lesion removal (endometrial polyp, type 0 or I leiomyoma) compared with conventional resectoscopy 27 28 29. Potential disadvantages of these systems include the cost of the disposable devices along with their associated fluid management systems; the lack of electrosurgical element in some of these types of devices, resulting in the inability to cauterize bleeding vessels; and limited data on the capability to treat type II leiomyomas 30. Additionally, type II leiomyomas may be more difficult to remove with these devices, compared to the loop resectoscope that could dissect the myoma from surrounding myometrium. Blind removal is not indicated where instrumentation for guided removal is available 21.

The use of office hysteroscopy has been well established for the diagnostic evaluation of abnormal uterine bleeding 36. Appropriate patient selection for office-based hysteroscopic procedures for women with known uterine pathology relies on thorough knowledge and understanding of the target pathology, size of the lesion, depth of penetration of the lesion, patient willingness to undergo an office-based procedure, physician skills and expertise, assessment of patient comorbidities, and availability of proper equipment and patient support. For example, patients with medical conditions, such as sleep apnea or cardiopulmonary disease, may not be appropriate candidates for office-based intravenous sedation without the presence of an anesthesia care team. Consideration for performing hysteroscopy in an alternative setting, such as the operating room or ambulatory surgery center, should be made for patients who have anxiety or have previously failed or not tolerated the office-based procedure.

Neuronal loss parallels the distribution of neurofibrillary tangles in AD, and it is a better correlate of cognitive deficits than the tau burden [91]. Still neurons with tangles can be long lasting, perhaps persisting as ghost tangles for decades [23]. Perhaps more importantly, it appears that synaptic loss precedes neuronal loss, and these effects are probably driven by amyloid and tau pathology [92, 93]. Numerous studies of synaptic protein markers and as well as electron microscopy have documented synaptic loss in AD and amnestic mild cognitive impairment that is thought to precede AD [92]. Synaptic loss appears to be the strongest correlate of cognitive decline in AD surpassing the associations with neuronal loss and tau burden [94]. Cognitive decline and decreases in verbal fluency early in AD are believed to reflect these decreases in synaptic density in the hippocampus and medial temporal lobes. One of the earliest studies demonstrated that declines in synapses are likely the result of axonal dysfunction affecting the presynaptic termini [95,96,97]. Gene expression studies in AD validate these findings, as proteins involved in synaptic vesicle trafficking and neurotransmitter recycling, in addition to structural elements of the synapse, are affected [92]. These pathogenic changes appear to be directly related to AD pathology, and their effects on synaptic function are associated with clinical symptoms. The route of synaptic damage may be multifocal, as impaired axonal transport resulting from tau dysfunction may be complemented by the arrival of hyperphosphorylated tau in dendritic spines and concomitant impaired synaptic transmission [98]. Interestingly, it is noted the remaining synapses become larger and more robust, lending credence to a compensatory synaptic hypothesis in AD [23].

Lewy body dementia is a term that encompasses dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) [119]. Lewy related pathology is associated with pathologic deposition of α-synuclein in neuronal cell bodies as Lewy bodies and neuronal cell processes (mostly axons) as Lewy neurites. Specific neuronal populations in the central and peripheral nervous systems are vulnerable to Lewy-related pathology. In Lewy body dementia, Lewy related pathology affects corticolimbic regions and is often associated with concurrent Alzheimer type pathologic change [120, 121]. In addition Lewy related pathology has been reported to be frequent in the substantia nigra of AD, and for a time it was suspected that patients with PD and coincident dementia had mixed (AD-PD) pathology [18, 23]. Now it is accepted that patients with Lewy pathology can have dementia caused strictly by the Lewy pathology, and this can be observed in patients who exhibit Parkinsonian clinical symptoms first, as in PDD, and those who develop dementia first, as in DLB. Almost a quarter of AD patients develop Parkinsonian features, but the relative contribution of substantia nigra tangles and Lewy bodies to this presentation is unresolved [122]. Lewy bodies in AD do not follow the same pattern of selective vulnerability associated with PD. In particular, Lewy pathology in AD is most frequent in olfactory bulb and the amygdala [23, 123]. The clinical significance of olfactory and limbic Lewy related pathology is uncertain. In the Mayo Clinic Brain Bank approximately 33% of the cases with AD also have Lewy related pathology as a secondary finding, and work is being carried out to determine what factors contribute to comorbidity. Evidence suggests that Aβ can directly affect α-synuclein toxicity, and it is also known that tau protein and α-synuclein can directly interact promoting their co-assembly [124,125,126]. Moreover there are several candidate genetic risk factors that overlap for AD and PD, most notably APOE and MAPT [127]. 041b061a72