Natasha Spencer, MD

• Department of Emergency Medicine
• Mount Sinai School of Medicine
• New York, New York

In their seminal article &om 1985 prostate zonal anatomy mri uroxatral 10 mg purchase online, Kurman and colleagues vaguely describe the architecture of simple hyperplasia as an increase in the number of glands resulting in crowding that ranges from mild to short of back-to-hack prostate oncology dr mark scholz cheap uroxatral line, and glandular shapes that may be altered due to cystic dilatation or mild irregularities in outline mens health 60 day transformation buy uroxatral australia. Just as a villous adenoma with areas of cribriforming is at a much higher risk for the development of colonic adenocarcinoma than the architecturally simple tubular adenoma mens health how to last longer in bed purchase uroxatral 10 mg without a prescription, endometrial lesions with increasing architectural complexity are associated with an increasing risk of myoinvasion106 prostate cancer 911 doctor samadi cheap uroxatral 10 mg with amex. I agree with those who continue to distinguish simple from complex architectural patterns based upon the degree of contour abnormalities of the constituent glands as described at the beginning of this paragraph, despite the more subjective nature of this approach. Although assignment of a given hyperplastic process to a simple versus complex category can be problematic, this descriptive feature is not what drives clinical management in this classification system. Instead, it is the assessment of cytologic nuclear) atypia within a hyperplastic glandular proliferation that determines whether a diagnosis of atypical hyperplasia is rendered. Cytologic atypia is recognized by variable combinations of nuclear enlargement, loss of polarity, stratification, rounding, contour irregularities, prominent nucleoli, and chromatin abnormalities that are most often manifested as chromatin clearing. Some investigators have attempted to grade the degree of cytologic atypia as mild, moderate, or sevete, but these subdivisions are not reproducible, lose relevance in a biologic system in which some well-differentiated carcinomas exhibit less cytologic atypia than some examples of atypical hyperplasia, and have not been shown to further stratify risk of progression to carcinoma. Determinarion of the presence or absence of cytologic atypia is subjective and poorly reproducible, which bas a direct and adverse impact on the ability to reliably separate abnormal endomet:rial proliferations into the clinically relevant categories of atypical versus nonatypical bype. I concur with those investigators who emphasize the importance of nuclear atypia re/4tiw to the nuclear features of nonhypcrplastic endometrial glands elsewhere in the speci· men. Artifacts related to fixation and processing can also result in perceived nuclear abnormalities such as chromatin clearing. Whenever possible, a conscious comparison of the nuclear features of the potentially atypical glandular proliferation should be made to what passes for normal in a given sample, which will help to avoid the overdiagnosis of cytologic atypia. This aercise is particularly important when considering a diagnosis of simple atypical bype. In addition to the problems of reproducibly distinguish· ing simple from complex hype. Bo1h of these examples were taken from aJthitecturally unremarkable proliferative endometria, and the nuclear features depicted were present throughout all of the glands. Over the course of decades, pathologists and clinicians have been indoctrinated with the terms hyperplasia and atypical hyperplasia, and clinip clans an: comfortable making treatment decisions based upon this classi6cation system. I suspect thar pathologists ha~ difficulty keeping these terms straight, let alone clinicians. The effort required to con~rt pathologists and clinicians to this terminology, with its attendant risks for confusion and inappropriate clinical man· agement, should not he underestimated. Although this system has not been validated, it represents a logical amalgamation of what I interpret as the most desirable features of each system. Higbp lights of this hybrid dassi6cation system are outlined below: · As advocated by the Stanford group, a glancJs. For lesions with simple architecture, obvious and diffuse atypia is necessary before the process is categorized as atypical. To summarize, the degree of cytologic atypia required for an "atypical· designation is in~rscly propor· tiona! The degree of atypia that trig· gcrs a malignant diagnosis is depicted in discussions of these entities. When esti· mating this ratio, the space occupied by the gland lumens and villoglandular structures is included in the glandular comparunent. The glands are predominantly tubular, exhibit some cystic dilatation, and are lined by pseudostratified cells wi1hout nuclear atypia. There is ample stroma separating 1he glands, but the glands-to-stoma ratio exceeds 2 to 1. This example consists of closely packed tubular glands of varying caliber that lack cytOlogic atypia and demonstrate a simple rather than complex architectural pattern. The macroglandular units of this hyperplastic proliferation are separated by variable amounts of stroma and contain internal papillary structures that lack second or third degree branching. This complex glandular proliferation lacks cytologic atypia and the glands are surrounded by a moderate amount of stroma. In this lesion, cytOlogic atypia is manifested by nuclear rounding, nuclear enlargement, distinct nucleoli, chromatin clearing, and epithelial stratification. Although the rate of progression to carcinoma reported in the 1985 study by Kunnan et al. These data provide strong support for upgrading the substantial proportion of cases that would traditionally be considered complex hyperplasia without atypia to "complex atypical hyperplasia (based on architecture)· when there are back. Topography of Endometrial Hyperplasia Endometrial hyperplasia may present as a focal. These lesions lack conventional features of cytologic atypia and are composed of architecturally complex, back-to-back glands with threadlike strands of intervening stroma. Although the glands are complex, the mazelike, labyrinthine pattern of adenocarcinoma is absent. A: An island of hyperplasia is present within a background of proliferative endometrium. B: the hyperplastic focus exhibits some cytOlogic atypia and consists of an admixture of simple and complex architectural patterns with focal morular metaplasia. In addition, the terms focal and di£iUse lack precision and are subjeaively applied to endometrial lesions. A: this low-magnification view demonstrates a mari<edly thickened endometrium composed of crowded glands with a variety of sizes and shapes. B: Numerous papillary infoldings in these crowded glands creates a pattem of architectural complexity. Foam Cells in Endometrial Hyperplasia Aggregates of stromal foam cells are most often seen in the setting of endometrial hyperplasia or well-differentiated adenocarcinoma. Although originally thought to represent a modified stromal cell, the consistent immunoreactivity of foam cells with the macrophage marker J<P. Hyperplastic glands with cystic dilatation impan a spongy appearance to ponions of the lesion. The glands-to-stroma ratio cannot be properly evaluated in areas where the stroma has been expanded by aggregates of foam cells, such as in the left side of the image. Whenever possible, the diagnosis should he based upon areas where stromal foam C(:Us arc absent or inconspicuous; if the architecture of the entire sample is altered by dusters of foam cells, the repon should include a cautiorwy note about the possibility of underdiagnosis with a recommendation for close follow-up with consideration for resampling. Behavior of Endometrial Hyperplasia the risk of progression ofsimple hyperplasia without atypia to carcinoma is negligible and within the range seen in the general population as a whole. However, this percentage is based upon the experience ofa single patknt out of 13 similarly diagnosed patients who progressed to well-differentiated adenocarcinoma over a 5-year period. In stark contrast to these data, Longacre and colleagues claim an incidence of myoinw. Differential Diagnosis of Endometrial Hyperplasia the differential diagnosis of endometrial hyperplasia includes (a) dissociation, coiling. The distinguishing features of these processes are discussed elsewhere in this chapter, hut a few points deserve reiteration. Whenever contemplating a diagno· sis of localized hyperplasia on the low end of the spectrum or a loc:al. Another poten· tia1 mimic of a localized endometrial hyperplasia relates to the common finding of increased glandular density within the basalis. Although generally not given more than a passing glance in hysterectomy specimens, this phenomenon can be misinterpreted as hyperplasia (with atypia in cases of "activated" nuclei) when encountered in fragments of tangen· tially cut endometrial samples. Note how tangential sections through fragments of basalis could simulate endometrial hyperplasia. Metaplastic hypcrplasias could just as easily be referred to as hyperplastic metaplasias, but use of the former tertn is preferred to emphasize that these processes should be regarded as a form of hyperplasia. As fOr hyperplasias of the usual type, it is recommended that metaplastic hyperplasias measure at least 1 mm in a single tissue fragment befOre being diagnosed. Metaplastic hypcrplasias without atypia are not thought to be clinically significant lesions, and can be considered to be within the spectrum of ordinary metaplasia. Although there arc limited outcome data on atypical metaplastic hyperplasias, they may be associated with low~grade adenocarcinoma dse~ where in the endometrium. When there is significant glandu~ lar crowding and complexity with scant intervening stroma. The figures in this section will help to convey my approach to this difficult area. Some metaplastic proliferations fit the definition ofa hyper· plasia by virtue ofa glands-t~stroma ratio of>2 to 1, but exhibit little architectural complexity. Glands lined by ciliated cells exhibit an architecture similar to that of the mucinous lesion in the preceding figure. As metaplastic hyperplasias increase in architectural com~ ple:xity, their classification becomes more controversial. As a practical matter, the presence of numerous ciliated cells in an endometrial proliferation is strong evidence in favor ofa benign process, since adenocarcinomas composed predominantly of ciliated ceUs arc quite rare. These moderately crowded metaplastic glands represent a form of mucinous metaplasia that is not thought to be associated with a significant risk of concurrent or subsequent carcinoma. Glandular complexity is minimal and manifested primarily by undulating folds of mucinous epithelium without nuclear atypia. The ciliated cells have round to oval, bland nuclei, some of which surrounded by a clear halo. Despite the bland nuclear features, the architectural complexity suggests that this lesion is best managed as an atypical hyperplasia. Classification ofcytologically bland mucinous endometrial pmlifcrarions with marked an:h. The pathology report should indicate that the findi~ an: suspicious for lowpgrade mucinous cucinoma, or that this possibility cannot be cx:duded. In terms of differential diagnosis, mucinous mctaplasp tic lesions of the endometrium with a micmacinar an::h. Endometrial curettings may also be contaminated by shredded, compacted strips of benign endocervical mucinous epithelium that may be mis· taken for architecturally complex mucinous lesions of endo· metria! Both of these lesions presented as nonlocalized findings within endometrial curettings. In this setting, the finely papillary and focally microacinar architecture is a worrisome feature, despite the bland nuclear features. Localized hyperplastic papillary proliferation with mucinous metaplasia involving the endometrial surface. Note the fibrovascular cores within most of the papillary structures and the bland nuclear features. Lehman and Hart have described a localli:ed hyperplastic proliferation that features a papillary architecture and associated metaplastic epithelial changes, which are usually of mucinous, eosinophilic, and/or ciliated cdl type. When small and localized, and particularly when confined to an endomctt:ial polyp as is often the case, these lesions can be n:gardcd as incidental 6ndings. Note the simple papillary architecture and bland nuclear features of this surface lesion, which facilitate its distinction from vi lloglandular endometrioid adenocarcinoma. As these various types of papillary proliferations increase in architectural complexity and become less localized, their clas· sificarion becomes more subjective and conuoversial, and data on their natural. The recommendations out· lined earlier in the discussion of architecturally complex: muci· nous endometrial proliferations apply to this situation as well. Although this is a larger and more architecturally complex lesion than the one in the preceding figure, it is confined to an endometrial polyp and has bland nuclear features. The papillae impart some architectural complexity, but there is ample stroma separating the glands and there is no cytologic atypia. This lesion could also be referred to as metaplastic hyperplasia with papillary eosinophilic cell change without atypia. Endometrial cancer patients who arc most likely to benefit ttom such studies include those (a) younger than 50 years of age, (b) with a personal or f. Such studies should be performed only at the request of the clinician and afier patient oonsent has been obtained. Although the nuclear features of this lesion are similar to those illustrated in the preceding figure, the more crowded architectural pattern warrants the designation *atypical. When seen in endometrial proliferations that are not worthy ofa diagnosis of adenocarcinoma. Endometrioid carcinomas are "Type I" twnors that are related to exposure to increased levels of estrogenic substances, which may be associated with one or more of the following: obesity, diabetes, infertility. The special situation in which dual endometrioid carcinomas of the endometrium and ovary are found. This longitudinal section through 1he tumor reveals an elevated, tan nodule as demarcated by the arrowheads. Gross detection of myometrial invasion is often more difficult in fresh as opposed to fixed specimens. The depth of invasion, as indicated by 1he vertical arrow, does not include 1he portion of the tumor that protrudes above 1he nonnal endometrial-myometrial junction (see section on myometrial invasion). The pathology report of resected endomettial carcinomas should include the following information: tumor type, tumor grade, depth of myometrial invuion, presence or absence of angiolympbatic invasion, status of the cervix, and presence or absence of involvement of any other submitted tissues (ovaries, fallopian tubes, lymph nodes, etc. Specks and/or geographic islands of pasty yellow material may represent either foci of neaos. In those tumors with myomettial infiltration, the blending of tumor with muscle often results in a rubbery tex:ture. Microscopic Features Gross Features Endometrioid carcinomas vary from polypoid masses to i. This discussion is restricted primarily to the histology of the superficial aspects of well-differentiated endometrioid card· nomas as encountered in endometrial biopsies and curettings. B: Longitudinal section of a different endometrioid carcinoma following formalin fixation with polypoid (upper left) and deeply invasive (lower right) components. A: Lightly fixed section of plaque-like tumor with superficial myometrial invasion. B: this section through a formalin-fixed tumor demonstrates invasion imo the inner half of the myometrium at left.

In these two separate examples prostate cancer incidence buy 10 mg uroxatral mastercard, note the full-1hickness atypia and crowding of 1he dysplastic nuclei and the presence of scattered mitotic figures 1hroughout all levels of 1he epithelium androgen hormone queen uroxatral 10 mg order fast delivery. Scattered mitotic figures are present throughout the dysplastic portion of the epitheliwn prostate cancer and sexual health buy cheap uroxatral 10 mg online, and atypical mitoses are usually readily apparent androgen hormone imbalance in women generic uroxatral 10 mg buy line. B: Involved gland with squamous maturation cells with abundant eosinophilic cytoplasm prostate health complex buy uroxatral 10 mg without a prescription, sometimes in association with keratinization and/or intercellular bridges). The dysplastic cells in both cases have high nuclear to cytoplasmic ratios, but exhibit different types of chromatin abnormalities. However, these lesions can he subtle and pose diagnostic difficulties in cytologic pn:parap tions, just as they do in histologic sections. S There is preservation of cell polarity and the nuclei are rc:gulady spaced from one another. Isolated cells with n:cognizable dysp plastic nuclear features are usually pn:sent. Features of endocervical gland involvement are present, as characterized by occasional cells with flattened nuclei at the periphery of the cellular aggregate (arrowhead) and smooth. The partially detached epithelial strip to the left of the arrowhead shows nuclear palisading. In this conventional Pap smear, linear streams of severely dysplastic squamous cells have formed that could be mistaken for histiocytes at low magnification. In Pap smears, severely dysplastic cells with exttemdy hyperchromatic nuclei, at least some of which have dense, orangeopbilic cytoplasm, are char. The backgrowtd often contains keratinous debris that may simulate a tumor diathesis, and dysplastic cells with spindle and tadpole shapes may be present. As discussed in the section on the Pap smear diagnosis of invasive squamous cell carcinoma, the resulting cytologic appearance can be virtually indistinguishable from invasive keratinizing twnors. The overlying layer of parakeratosis may prevent cytologic sampling of lhe dysplastic squamous cells in lhe deeper layers and result in a false negative Pap smear. A: this histologic section demonstrates the abnormal surface keratinization, which is associated wilh loosely adherent keratinous debris that contains dysplastic squamous cells. However, lha nuclear contour is smooth and this was ona of only a taw abnormal calls present in the smaar. These high-magnification images of two different cervical biopsies highlight the common finding of glycogenated squamous cells with perinuclear halos. Although not apparent at this magnification, the nuclei are of comparable size to that of normal intermediate cells, and these histologic features were present over continuous. Distinction ofkoilocyrosis from pagetoid dyskeratosis is discussed in the section on reactive and reparative processes. Mild nonspecific changes resulting in resemblance to koilocytosis (no significant abnormality). Perinuclear halos and irregular nuclear contours may result in an interpretation of koilocytosis. Tangential sectioning through the basal region of a metaplastic gland accoums for the solid cellular nodule of metaplastic cells in the lower left portion of the image. Immature Squamous Metaplasia In immatwe squamous metaplasia, there is a gradual replacement of endocervical colwnnar mucinous epithelium by parabasaltype squamous cells. Nuclear enlargemem of isolated mature squamous cells in a Pap smear from a postmenopausal woman. This so-called ·atypia of maturity* is best interpreted as being within normal limits. Although the nuclear chromatin may appear mildly abnormal in immature squamous metaplap sia, it is fairly unifonn throughout, and does not c:xb. The n:gularity in the spacing of nuclei and the presence of nudcoli also favor a metaplastic process, as does the presence of residwal mucinous epithelial cells on the surface. Atypical Immature Squamous Metaplasia There exists a subset of borderline squamous metaplastic lesions that ble. Patients with problematic lesions that remain difficult to subcategorize should receive dose clinical follow-up. B: Atrophic exocervical squamous epithelium from two different postmenopausal women. Atrophy Atrophy of exocervical and vaginal squamous epithdium is due to estrogen deprivation and is characterized by a thin layer of mitotically inactive basal and parabasal cells with oval to elongate nuclei. There is some overlap between the histologic features of atrophy and transitional cell meta~ plasia. Recognition of the uniformity of nuclear size and the lack of abnormalities in nuclear chromatin and contour in the mono· layer portion of these sheets facilitates this distinction. Another possible source of misdiagnosis in some inflamed, atrophic smears is the presence of "blue blobs," which appear to repre-sent mummified parahasal cells with precipitated hematoxylin. In postmenopausal women with atypic:al atrophic smears, a short course of estrogen therapy followed by a repeat Pap smear will often clarify the situation. The sheet is thicker in 1he left side of the image, where it gives the false impression of nuclear crowding. When the origin of the invasive <:arcinoma an be pinpointed, the depth of invasion is measured from the basement membrane of the originating epithelium to the deepest point of invasion. This sagittal section through a necrotic cervical cancer demonstrates involvement of the bladder anteriorly and the rectal wall posteriorlv. This exophvtic tumor protrudes from the external cervical os (the cervix has been amputated from a radical hysterectomy spetimen!. Wilous cell carcinoma and its variants account for approximately 75% of invasive carcinomas of the cervix. Although the mean age at presentation is 50 to 55 years, approximately 25% of tumors occur in patients under 35 years of age. Patients usually present with abnormal vaginal bleeding and/or an abnormal Pap smear; those with small tumors may be asymptomatic. Wilous cell car<:inoma almost always involves the transformation zone and may be polypoid, papillary, nodular, diffusely infiltrative, or ulccrated. The sec:tioned surfac:e of squamous <:ell carcinoma is usually gray-white and is sometimes punctuated by numerous minute specks of soft, pale yellow, paste-like material. A: this bivalved uterus exhibits diffuse replacement of the cervical wall by tumor. B: this longitudinal section through a fixed uterus demonstrates an ulceroinfiltrative tumor involving the full thickness of 1tte cervical wall. In B, the microinvasive focus also has scalloped contours and has elicited a stromal response manifested by edema and chronic inflammation. Wilous matura· tion, usually in the form of a modest increase in the amount of eosinophilic cytoplasm (more pink and less blue at low magn. An invasive process is indicated by the combination of (a irregular tongues of epithelium projecting from large crypt-1 ike structures, Ib) squamous maturation, lcl central necrosis within some of the nests, ldl associated chronic inflammation and edema, and le) in some cases, finding the abnormal epithelial nests located beneath the level of normal endocervical glands. Since the point of origin of these tumors is generally inapparent, the depth of invasion is measured from the basement membrane of the surface epithelium to the deepest point of invasion (arrows. In the lower right image, the lack of a connection between the abnormal epithelial nests and the overlying epithelium implies that the tumor seen in this section represents an extension of tumor located out of the plane of sectioning that has burrowed into the cervical stroma. A diagnosis of miaoinvasion requires that the entire lesion is present for evaluation, since a ttansected microinvasive focus or a small biopsy with super:6cial invasion may represent the "tip of the iceberg" of a much more aggressive twnor. Whenever stromal invasion is identified, the presence or absence of angiolymphatic invasion should be indicated in the pathology report (see section on retraction artifact near the end of this chapter for a discussion of the distinction between true angiolymphatic invasion and artifactual clefts surrowtd. In addition to the status of angiolymphatic invasion, reports of specimens with microinvasion should indicate the depth of strom. Stage lal tumors with angiolymphatic invasion and stage Ia2 tumors with or without angiolymphatic invasion have about an 8% risk of lymph node metastasis, which supports the use of pelvic lymphadenectomy as part of the treatment plan for these patients. This nonkeratinizing tumor exhibits stromal invasion by irregularlv shaped nests and anastomosing tongues of malignant squamous epithelium. This keratinizing tumor exhibits keratin pearl formation (arrolllf1 and jagged points project from the nests of infiltrating tumor. Keratin formation ami intercellular bridges are hallmarks of squamous differentiation. The tumor cel1 nests vary in size, and typically have a jagged or irregular contour, although rounded. The stroma generally reacts to twnor infiltration with varying combinations of chronic inflammation, edema. Keratin pearls ate typically found within the center of the nests, and consist of concentric whorls of keratin that in this context ate often associated. Infiltrative growth patterns, prominent interc:ellular bridges, and distinct ceU borders ate more typical of keratinizing tumors. This nonkeratinizing tumor infiltrates as closely packed anastomosing nests with rounded contours. This composite image highlights lhe nuclear features of two separate nonkeratinizing tumors. A rare, highly differentiated form of keratinizing squap mous cell carcinoma has been reported that exhibits extensive keratinization. Tumors with these features, when rigorously separated from small cell neuroendocrine c:arcinoma, behave similarly to conventional squamous carcinoma. The diagno· sis of adenosquamous c:arcinoma is reserved for tumors with both malignant squamous and glandular differentiation that is readily apparent in routinely swned sections. Squamous cell c:arcinomas are often divided into weD, moderately, and poorly differentiated forms. Sentinel lymph node biopsy, which is considered standard ofcare in the treatment of selected invasive breast carcinomas and cutaneous melanomas, is increasingly being utilized in the staging of patients with inV;t. Sive process may be absent in an individual case, whereupon one must rely on low-magnification architectural features to recognize stro~ mal inV;t. The inset shows a lymph node metastasis with recapitulation of this pattern (note the thin rim of rettaction artifact). Squamous cell carcinomas with clear cytoplasm due the presence of abundant glycogen. The extent and depth of this process at low magnification indicates an invasive lesion, but the sharply demarcated tumor cell nests have rounded rather than jagged contours and elicit only a mild and focal stromal response. Invasive squamous cell carcinoma with clear cell areas due to lhe presence of abundam inttacvtoplasmic glycogen. The blue-green, granular material that represents a tumor diathesis clings to scattered malignant squamous cells. Cytologic features of Squamous Cell Carcinoma In Pap smears, the malignant cells of frankly invasive squamous cell carcinoma are found both singly and in clusters. These cells are often associated with a twnor diathesis ("dirty backgro~md"), which. The components of a twnor diathesis include broken down blood products and necrosis-related granular debris associated with proteinaceous fluid. Although similar back· grounds can also be seen in benign conditions such as severe Trichomonas. In liquid-based smears, the granular debris of a tumor diathesis, which has been likened to blue-green rotton candy, tends to be loosely adherent to and intermingled with tumor cells in a pattern that has been referred to as a clinging diathesis. Since (a) there is often not a sharp cytologic distinction between keratinizing and nonkeratinizing tumors (both of which can show individual ceU keratinization) and (b) a given smear may show features of both tumor types, the Bethesda System has chosen not to subdivide squamous cell carcinomas into keratinizing and nonkerat:Wzing types. Nevertheless, it is instructive to discuss their general cytologic features separately. No definite tumor cells were found in this smear, but subsequent evaluation revealed invasive squamous cell carcinoma. A: Two elongated, wispy, orangaophilic cells with spindle-shaped, pyknotic nuclei are present. B: this image shows a monsttous orangeophilic tadpole cell with a large, intensely hyperchromatic nucleus located at 1he wider end of the cell. Nuclear detail is often obscured by intense hyperduomasia or pyknosis, hut some tumor cells with enlarged nuclei, coarsely granular chromatin, and nuclear contour abnormalities are usually apparent, and prominent nucleoli are seen occasionally. The tumor cells of nonkeratinizing squamous cell carcinoma also have enlarged nuclei with coarsely clumped chromatin, but are more likely to exhibit round nuclear contours, prominent nucleoli, cyanophilic cytoplasm, and lesser degrees of nuclear pleomorphism than keratinizing tumors. The presence of"blue blobs" in smears of atrophic vaginitis heightens the potential for misinterpretation as a malignant process. U6 Basaloid Squamous Cell Carcinoma Basaloid squamous cell carcinoma of the cervix is rare, but is probably undem:ported. Distinction from small cell carci~ noma, large cell neuroendocrine carcinoma, and the solid vari~ ant of adenoid cystic carcinoma are discussed with these entities elsewhere in this chapter. To avoid ronfusion with the much less aggressive adenoid basal carcinoma, the ambiguous tenn "basa~ loid carcinoma" should not be used. The inset shows tumor cells from a different case in which prominent nucleoli are evident. These tumors may recur locally, but do not metas-tasize if strict histologic criteria are used fOr their diagnosis. Reports of metastasizing verrucous carcinomas, such as case 2 in the report by Degefu et al. Warty Condylomatous) Carcinoma Warty (condylomatous) carcinoma is another rare variant of squamous carcinoma with a warty surface that exhibits mature squamous differentiation. These tumors are distinguished from verrucous carcinoma by the presence ofinvasive tumor cell nests that display (a) scattered central fOci ofkoilocytosis and (b) sig~ ni6cant nuclear atypia and mitotic activity in the cell layers near the epithelial-stromal interface. As is the case fOr verrucous carcinoma, then: is more experience in the literature with vulvar tumors of this unusual type. At higher magnification, some of the tumor cell nests are found to exhibit peripheral nuclear atypia wilh mitotic activity (left) and central koilocytosis (right. Such tumors may be designated papillary transitional cell carcinoma75 or papil~ lary squamotransitional cell carcinoma,t43 recognizing that classi6cation of these various subtypes of papillary carcinomas is a subjective exercise. Verrucous carcinoma is distinguished from papillary squamous cell carcinoma by its bland nuc:lei and broad, pushing interface with the underlying stroma, whereas warty carcinoma features prominent koilocy· tosis that is lacking in papillary squamous cell carcinoma. Confluent nests of well-differentiated squamous epithelium infiltrate the cervical stroma.

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Women in early labor are confined to bed if they are too uncomfortable to move about safely or if care maneuvers require it prostate oncology 76244 uroxatral 10 mg low price. However prostate 5lx side effect uroxatral 10 mg buy without a prescription, this position obstructs venous return androgen hormone zyklus cheap uroxatral 10 mg otc, thence cardiac output anti-androgen hormone therapy purchase genuine uroxatral on-line, leading to hypotension (supine hypotensive syndrome) mens health 082012 order 10 mg uroxatral with visa. The supine left lateral position keeps the uterus off the inferior vena cava, thereby improving cardiac output. Changing positions to improve maternal comfort and optimize fetal position are encouraged as long as not otherwise contraindicated by other maternal or fetal conditions. Other laboring positions might include sitting or crouching, and the use of special "birthing chairs," labor balls, or variously configured tubs of warm water. The dorsal lithotomy position is most commonly used for spontaneous and operative vaginal delivery in the United States. Fluid Management and Oral Intake Because labor is associated with decreased gastrointestinal peristalsis, aspiration during the administration of anesthesia is a concern. Patients in active labor should avoid oral ingestion of anything except moderate intake of clear fluids, occasional ice chips, and preparations for moistening the mouth and lips. When oral intake is not possible or is insufficient, intravenous therapy with 1/2 normal saline or D5 1/2 normal saline is indicated. Normal saline can be used if increased oncotic pressure is desired, but lactated fluids are generally contraindicated because of the metabolic acid deficit incurred by the lactate administration. Individual patient considerations, clinical considerations, and anticipated duration of labor will guide choice of intravenous therapy. The method chosen may depend on risk assessment at admission, the preference of the patient and the obstetric staff, and department policy. Risk factors for fetal intolerance of labor may include, but are not limited to , vaginal bleeding, acute abdominal pain, temperature >100. In the absence of risk factors on admission, the standard approach to fetal monitoring is to determine, evaluate, and record the fetal heart rate every 30 minutes in the active phase in the first stage of labor, and at least every 15 minutes in the second stage. In the presence of risk factors, fetal surveillance should be performed using either intermittent auscultation or continuous fetal monitoring using the following methods: During the active first stage of labor, auscultation should be performed every 15 minutes, preferably before, during, or after a contraction, and continuous monitoring should be evaluated at least every 15 minutes. During the second stage of labor, the fetal heart rate should be monitored every 5 minutes using either the intermittent or continuous procedure. If electronic fetal monitoring is used, an external tocodynamometer is initially used to assess uterine activity, providing information regarding the frequency and duration of contractions but not their intensity. Pain Control Management of discomfort and pain during labor is an essential part of good obstetric practice. Some patients tolerate pain by using techniques learned in childbirth preparation programs. Unless contraindicated, pain relief to ameliorate pain of contractions should be made available on request to women in labor. During the first stage of labor, pain results from the contraction of the 229 uterus and dilation of the cervix. This pain travels along the visceral afferents, which accompany sympathetic nerves entering the spinal cord at T10­T12 and L1. As the fetal head descends, there is also distension of the lower birth canal and perineum. This pain is transmitted along somatic afferents that comprise portions of the pudendal nerves that enter the spinal cord at S2­S4. To provide relief from obstetric pain, the following methods of anesthesia and analgesia are used: · Epidural block: Infusion of local anesthetics or narcotics through a catheter into the epidural space. The most effective form of intrapartum pain relief in the United States, it can be used in either vaginal or abdominal deliveries and in postpartum procedures such as tubal ligation. An epidural allows for longer duration of labor analgesia or anesthesia, and may be partially regulated by patient-controlled mechanisms. Local anesthesia can be administered easily at the time of delivery to provide perineal anesthesia for a vaginal delivery. To determine which method of obstetric pain control should be used, the positive and negative aspects of each should be considered. Of the regional modes of analgesia, epidural anesthesia is superior to spinal anesthesia in that it can be left as a continuous source of analgesia and anesthesia during both the labor and delivery process. Spinal anesthesia provides good pain relief for procedures of limited duration, such as cesarean delivery or vaginal delivery when labor is rapidly progressing. Combined spinal­epidural anesthesia has advantages of both techniques, including the ability to titrate medications throughout labor with the epidural catheter and the rapid onset associated with spinal techniques. All of these types of regional anesthesia may be associated with a postdural puncture headache. However, combined spinal­epidural anesthesia greatly decreases the risk of spinal headache in the mother when using newer atraumatic needles and reduces the risk of sympathetic blockade, which could lead to hypotension. Local block may provide anesthesia for episiotomy and repair of vaginal and perineal lacerations; however, paracervical block may result in fetal bradycardia. General anesthesia is associated with complications such as maternal aspiration and neonatal depression. If properly administered, it is effective for most cesarean deliveries, but regional anesthesia is preferable. Management of Labor First Stage Evaluation of the progress of labor is accomplished by means of a series of pelvic examinations. Each examination should identify cervical dilation, effacement, station, position of the presenting part, and the status of the membranes. These findings should be noted graphically on the hospital record, so that abnormalities of labor may be identified. During the latter portions of the first stage of labor, patients may report the urge to push, which may indicate significant descent of the fetal head with pressure on the perineum. Pushing should be discouraged at this time in order to avoid traumatic swelling of the cervix caused by the attempt to force the fetus through an incompletely dilated cervix. Should this occur, additional time is needed for the swelling to resolve before complete dilation can be achieved. Similarly, if there are significant fetal heart rate decelerations, more frequent examinations may be necessary to determine 232 whether the umbilical cord is prolapsed or if delivery is imminent. Routine amniotomy is unnecessary if labor is progressing normally and evidence supports the fetus is tolerating labor. If needed, amniotic membranes may be ruptured to insert an intrauterine pressure catheter or a fetal scalp monitor. However, rupture of the membranes does carry some risk, because the incidence of infection may be increased if labor is prolonged, or umbilical cord prolapse may occur if rupture of the membranes is undertaken before engagement of the presenting fetal part. With the onset of each contraction, the mother is encouraged to either use open glottis pushing, or perform an extended Valsalva maneuver. This increase in intra-abdominal pressure aids in fetal descent through the birth canal. Alternatively, in low risk women who may not yet have the urge to push, a rest period of 1 to 2 hours may be offered at the onset of the second stage of labor. Molding is an alteration in the relation of the fetal cranial bones, even resulting in partial bone overlap. Some minor degree of molding is common as the fetal head adjusts to the bony pelvis. The greater the disparity between the fetal head and the bony pelvis, the greater the amount of molding. Caput succedaneum is the edema of the fetal scalp caused by pressure on the fetal head by the cervix. Molding and caput succedaneum are the two most common causes of overestimation of the amount of descent, that is, of the station of the presenting fetal part. An extended second stage may last as long as 2 to 3 hours, and the prolonged resistance encountered by the fetal vertex may prevent appropriate identification of fontanels and sutures. If identified before the second stage of labor, these changes should be noted on the pelvic examination and may indicate a potential problem in negotiation of the birth canal. Restricted use of episiotomy may facilitate delivery by enlarging the vaginal outlet and may be indicated in cases of instrumental delivery and/or protracted or arrested descent; however, there is currently no evidence based indication for use of episiotomy. With progressive labor and control of the fetal head and body at delivery, the risk of obstetric laceration with a normal-sized infant is low, so that the need for episiotomy is minimal. If an episiotomy is needed, it should be performed only after the perineum has been thinned considerably by the descending fetal head. The incision should be somewhat longer on the mucosal surface when compared with the perineal surface of the incision. Median episiotomy is associated with higher rates of injury to the anal sphincter and rectum, and mediolateral episiotomy may be preferable to median episiotomy in selected cases. This natural mechanism decreases the likelihood of laceration or extension of an episiotomy. To support the perineal tissues and facilitate extension of the head, a modified Ritgen maneuver is performed. This maneuver involves placing one hand over the vertex while the other hand exerts pressure through the perineum onto the fetal chin. A sterile towel is used to avoid contamination of this hand by contact with the anus. After delivery of the head, the shoulders descend and rotate to a position in the anteroposterior diameter of the pelvis. To avoid injury to the brachial plexus, care is taken not to put excessive force on the neck. Use of oxytocin immediately after delivery of the infant may shorten the third stage of labor and prevent uterine atony. Third Stage Delivery of the placenta is imminent when the uterus rises in the abdomen, becoming globular in configuration, indicating that the placenta has separated and has entered the lower uterine segment; a gush of blood and/or "lengthening" of the umbilical cord also occur. Pulling the placenta from the uterus by excessive traction on the cord should be avoided. Inappropriate application of force may result in inversion of the uterus, an obstetric emergency associated with profound blood loss and shock. Instead, it is 237 appropriate to wait for spontaneous extrusion of the placenta, sometimes up to 30 minutes. As the placenta passes into the lower uterine segment, gentle downward traction is applied to the umbilical cord, while the abdominal hand applies gentle suprapubic counterpressure (posterior and cephalad) to secure the uterine fundus and prevent uterine inversion. This is accomplished by passing a hand into the uterine cavity and using the side of the hand to develop a cleavage plane between the placenta and the uterine wall. The umbilical cord should be evaluated for the presence of the expected two umbilical arteries and one umbilical vein. After the placenta has been removed, the uterus should be palpated to ensure that it has reduced in size and become firmly contracted. Excessive blood loss at this or any subsequent time should suggest the possibility of uterine atony. The use of uterine massage as well as oxytocic agents, such as oxytocin, methylergonovine maleate (methergine), and prostaglandins 238 (carboprost or misoprostol), may be used routinely in the circumstance of excessive postpartum blood loss. The introitus, vagina, perineum, and the vulvar area, including the periurethral area, should be evaluated for lacerations. Repair of nonhemostatic lacerations are generally accomplished with an absorbable suture. It is more likely to occur in cases of rapid labor, protracted labor, uterine enlargement (such as from a large fetus, polyhydramnios, and multiple gestation), or intrapartum chorioamnionitis. Immediately after the delivery of the placenta, the uterus is palpated to determine that it is firm. Perineal pads are applied, and the amount of blood on these pads and maternal pulse and blood pressure are monitored closely for the first several hours after delivery to identify excessive blood loss. Labor induction can be 239 achieved with intravenous oxytocin administration, cervical ripening, and manipulation of the amniotic membranes. Oxytocin Administration the device used to administer oxytocin should permit precise control of the flow rate to ensure accurate, minute-to-minute control. These regimens vary in initial dose, amount of incremental dose increase, and interval between dose increases. Lower and less frequent dosage increases are associated with a lower incidence of uterine hyperstimulation. Higher and more frequent dosage increases may result in shorter time in labor and reduce the incidence of chorioamnionitis and the number of cesarean deliveries performed for dystocia (abnormal labor) and also in increased rates of uterine hyperstimulation. Cervical Ripening Cervical ripening may be beneficial if the cervix is unfavorable for induction. Misoprostol, a prostaglandin E analog, is an effective agent for cervical ripening and induction of labor. Because of the increased risk of uterine hyperstimulation, both drugs are contraindicated in patients who have had a previous cesarean delivery or previous uterine surgery. One method uses laminaria-hygroscopic rods made from the stems of the seaweed Laminaria japonica that are inserted into the internal cervical os. Another cervical ripening method is the placement of a 30 mL Foley catheter in the cervical canal, which is lower in cost than other forms of cervical ripening and carries a reduced risk of uterine tachysystole. Reasons for this increase include labor dystocia, nonmedically indicated early term births (37 0/7 to 38 6/7 weeks), use in breech deliveries, and use in situations in 241 which more sophisticated fetal monitoring is nonreassuring. However, evidence does not indicate a simultaneous improvement in maternal or neonatal outcomes. Decision Making: Mode of Delivery the decision regarding the mode of delivery should be made by the health care provider together with the patient. Advantages of a successful vaginal delivery include reduced risks of hemorrhage and infection; shorter postpartum hospital stay; and a less painful, more rapid recovery. Examples of indications for cesarean delivery include hemorrhage from placenta previa, abruptio placentae, prolapse of the umbilical cord, and uterine rupture, because these conditions require prompt delivery.

Patients who receive no opioids preoperatively or during the operative procedure will require analgesics in the immediate postoperative period once the inhalation anesthetic is eliminated prostate cancer prevention trial uroxatral 10 mg order with amex. Most cases of postoperative pain can be managed by the administration of small intravenous doses of opioids prostate cancer gleason score 6 discount uroxatral 10 mg overnight delivery, usually morphine prostate oil cheap 10 mg uroxatral fast delivery. This is important in a patient being weaned from the ventilator during the early postoperative 1036 ation for thoracic epidural analgesia prostate cancer 4th stage prognosis purchase cheapest uroxatral. This technique significantly reduces the respiratory depression and pulmonary mechanics abnormalities that accompany the quantity of systemic opioids that would be necessary to provide adequate analgesia for these excruciatingly painful incisions prostate 22 uroxatral 10 mg buy amex. If the procedure requires systemic heparinization, one would typically defer placement of these catheters until the heparin effect is neutralized. For the patient undergoing coarctation repair via a left thoracotomy, the caudal or epidural catheter is placed after demonstration of motor function in the lower extremities. Summary of Surgical Management the improvements in surgical technique, coupled with advancements in anesthetic and technologic support, makes repair in early infancy not only feasible, but in many cases preferable. Currently, repair in infancy can be offered for a number of congenital heart defects. Palliative surgery is entertained when a physiologic derangement requires intervention, but circumstances preclude definitive repair. In general, the recent trend in pediatric cardiovascular surgery has been to repair defects in infancy rather than palliate. This trend reflects improved technical capabilities coupled with a desire to limit the morbidity and mortality associated with longterm medical management and the sequelae of multiple palliative operations. Early infant repair may also have the selective advantage of enhancing organ system protection during repair because of poorly understood factors promoting resistance to injury and enhanced recovery potential. Early indications suggest that the latter procedure provides an anatomic correction with better longterm results. A second example of the continuing evolution of technique is surgery for tetralogy of Fallot. Long-standing pulmonary insufficiency after right ventricular outflow repair for tetralogy of Fallot is associated with right ventricular dysfunction and failure. There seems to be an improvement in myocardial perfusion, with higher diastolic pressures, lower aortic saturations, and decreased myocardial work. Several factors considered to be associated with an increased risk for single ventricle 74 AnesthesiA for surgicAl repAir of congenitAl heArt DiseAses 1037 13 generAl issues 1038 palliation include anatomic variants such as aortic atresia, mitral atresia, ascending aorta less than 2. Surgical management has evolved in a broader application of certain surgical procedures initially designed for a specific defect. Initially, the wider application of the Fontan operation to include complex defects once considered inoperable was associated with a rise in morbidity and mortality. The communication allows for right-to-left shunting, thereby preserving cardiac output at lower systemic venous pressure in the early postoperative period. When necessary, once the patient has convalesced from the acute postoperative changes, the fenestration can be closed at the bedside with a snare placed at the time of the operation or in the catheterization laboratory with a device. Ingenuity and innovation such as demonstrated with the difficult Fontan procedure have permitted continued improvements in survival for all patients with congenital heart disease. As incisions in the myocardium become smaller and sutures more precisely placed, and as improvements in surgical techniques continue to evolve, the complications of ventricular dysfunction, arrhythmias, and residual obstruction should decline, contributing to improved patient quality of life. One final difference unique to congenital heart surgery that has a major impact on anesthetic management relates to the type of cardiopulmonary support. Many operations are undertaken in this setting of extreme biologic conditions of temperature and perfusion. The major factors responsible for this are hemodilution and altered plasma protein binding, hypotension, hypothermia, pulsatility, isolation of the lungs from the circulation, and uptake of anesthetic drugs by the bypass circuit. Drugs in the blood exist in the free (unbound and therefore the active form) or plasma bound (inactive form bound to protein. The addition of the prime volume immediately reduces the protein concentration and the ratio of boundtofree drug in the circulation changes. A decrease in the plasma concentrations of medications as a result of hemodilution, shifts drugs down their concentration gradient from tissue to plasma. Hypothermia contributes to the changes in plasma concentrations primarily by depressing enzyme function and slowing the metabolism of medications. Drug metabolism is diminished during hypothermia; enzyme activity is halved for every 10°C reduction in temperature. This may explain the secondary increases in plasma concentrations of opioids reported during the rewarming phase. These medications are released when systemic reperfusion is established and concentrations are transiently increased. Anesthetic requirements decrease with systemic hypothermia, but as rewarming is initiated, additional anesthetic drugs, including a benzodiazepine, are added to the pump to ensure that anxiolysis/amnesia is maintained. The duration of the pre-bypass period varies greatly, particularly in children who have had previous surgeries, and maintaining hemodynamic stability for pro longed periods of time can often be challenging. For children undergoing repeat sternotomy, blood products with an appropriatecapacity blood warmer should be readily available in case of emergent need. Older children receive plasmalyte, a balanced electrolyte solution, at a reduced maintenance rate, allowing the administration of 5 percent albumin, if necessary, for volume augmentation. It is not unusual for volume replacement to be necessary during placement of the cannula; and if the aortic cannula is already in place, it will be easy to coordinate the administration of volume between the anesthesiologist and perfusionist, while the surgeon completes cannulation. Calcium chloride, 10 mg/kg, is also frequently useful to support hemodynamics at this time. Hypothermia causes a host of other effects, including decreases in receptor affinity. The number of receptors available for interaction with a ligand will determine the subsequent magnitude of a drug effect. A reduction in the number of cardiac receptors has been observed in congestive heart failure, and defects in receptor transduction and impairment of synthesis and reuptake of norepinephrine occur. Changes in receptor density and function may occur very quickly and have been observed to occur during cardiac surgery. Other methods of measuring anticoagulation include the Hepcon system (a plasma heparin concentration assay), which may allow for more accurate titration of heparin and protamine dosages. In most centers, bicaval cannulation is used for all, but the smallest children (< 2 kg) to prevent venous return from interfering with the surgical field. Flow rates may be reduced during periods of hypothermia, although many centers now prefer to maintain greater flows throughout the bypass period. If the cannula inadvertently slips beyond the takeoff of the right innominate artery, preferential perfusion to the left side of the brain can be observed. Hypothermia is classified as mild (30°C­36°C), moderate (22°C­30°C), or deep (17°C­22°C). In general, lower temperatures are used for more complex operations that carry a greater potential for requiring periods of low-flow bypass or circulatory arrest. Cooling is primarily achieved extracorporeally through the heat exchanger in the bypass circuit, although some surgeons also request that ice be applied to the head. Aortic Cross-clamping and Intracardiac Repair Phase the aorta is crossclamped, with the heart then rendered asystolic after infusion of a highpotassium cardioplegia solution into the aortic root. Blood pressure may be controlled within the normal range using -adrenergic blockers or agonists. Phenylephrine is commonly used to increase blood pressure, and phentolamine is often used to lower blood pressure. The child is usually cooled at this stage, using the nasopharyngeal temperature as a guide. Cardioplegia is given by the perfusionist after cross-clamping the aorta to stop the heart and provide cardioprotection during the period of ischemia. Recent technical advances in the field of oxygenator construction and size and reduction of priming volumes to as low as 45 mL for neonatal oxygenators have allowed significant reductions of circuit volumes over the past decade. As the circuit prime volume is reduced, the dilutional effects of bypass become less dramatic, and plasma concentrations of anesthetic drugs should be maintained at a higher level compared with earlier reports. Also, tubing sizes can be reduced to 3/16-inch diameters, which, in combination with shorter length tubing, allow reduction of priming volumes to the range of 100 to 150 mL for neonates. An additional consideration is the success with circuit miniaturization and heparin-coated oxygenators and circuits. Heparin and biological coatings designed to minimize activation of proinflammatory mediators and endothelial cell damage are applied to oxygenators and tubing. This results in less production of kallikrein and bradykinin, which in turn reduces the secretion of tissue plasminogen activator from endothelial cells. Likewise, the optimal priming fluid in cardiac surgery is a topic of enduring debate. The addition of lactate to the prime increases postoperative serumlactate concentrations and should be avoided. This is often only detected by measuring the strong ion difference via the Stewart approach to the acid-base homeostasis. Both acidifying events are attenuated by the dilutional hypoalbuminemia induced by the administration of the pump prime. Because a hyperchloremic acidosis of a mild degree seems to be well tolerated and not associated with a poor outcome, no intervention seems necessary. The avoidance of dextrose is especially important during complex repairs using deep hypothermic cardiac arrest in which the risk of neurologic injury is substantive. Now a days a balanced electrolyte solution such as Plasmalyte is used for the crystalloid component of the prime. Platelet count decreases and coagulation factors, including fibrinogen, are diluted after bypass and these may contribute to a coagulopathy. The fibrinogen concentration at the end of bypass has been shown to correlate with the 24hour chest drainage in children weighing less than 8 kg. This is seen more frequently in infants and neonates in whom an average decrease in plasma concentrations of hemostatic proteins by 56 percent immediately on initiation of bypass can be observed. Overall, younger age represents the single most important risk factor for coagulopathy and bleeding complications. Depending on the size, age and complexity of the repair, a target hematocrit is chosen. If whole blood or packed cells are added to the prime, the target hemodilution range should be 28 to 30 percent; the prime should be recirculated continuously and warmed between 35. Other prime additives are heparin, antifibrinolytics, anti-inflammatory agents (aprotinin, corticosteroids), antibiotics, vasodilators, and sometimes, diuretics (mannitol, furosemide). At the end of the case and before separation from bypass, blood gas analysis is repeated to ensure that the electrolytes, glucose, and hematocrit are within a desired range. Acidbase changes and sodium concentration are corrected with sodium bicarbonate, and residual lactate is washed out with the help of the hemofiltration. Myocardial damage is related to both the duration of the aortic cross clamping and the effectiveness of the myocardial protection. Myocardial protection by using potassium containing cardioplegia is used routinely. Potassium concentrations in cardioplegic solutions ranging from 12 to 30 mEq/L are typically used to achieve cardiac standstill within 1 to 2 minutes under hypothermic conditions, with higher concentrations (or longer induction times) required for normothermic conditions. Myocardial edema after bypass and global ischemia can be reduced by a number of strategies that involve modifying the conditions of delivery and composition of cardioplegia solutions as they affect the movement of intracellular and interstitial fluid. In contrast to studies in adults, most studies conducted in newborns have shown little difference between 1041 13 generAl issues blood and crystalloid cardioplegia. The benefits of this approach appear to be optimal at myocardial temperatures between 24°C and 28°C. Avoidance or reduction of myocardial edema occurs by limiting the pressure of cardioplegia infusions and by providing moderately hyperosmolar cardioplegia solutions that contain blood. Close management of myocardial calcium balance to avoid extremes of intracellular hypercalcemia or hypocalcemia, especially during reperfusion, is very important. The addition of magnesium may solve this dilemma by preventing damage from higher cardioplegic calcium concentrations by its action as a calcium antagonist. This prevents mitochondrial calcium overload as a consequence of reperfusion injury. Magnesium also prevents the influx of sodium into the postischemic myocardium, which is exchanged for calcium during reperfusion. Every cardiac program has their own philosophy regarding cardioplegia and myocardial protection. In neonates and infants, albumin is added to the cardioplegic solution to maintain an appropriate colloid osmotic pressure. In children undergoing circulatory arrest, long crossclamp times, and large pump suction return cases, 20 mg/kg methylprednisolone is used up to a maximum of 500 mg, to reduce the production of inflammatory mediators that result in myocardial dysfunction. Mild degrees of hypothermia and certainly the avoidance of hyperthermia are essential in the perioperative period. Studies have shown that the temperature of the foot is more sensitive than the temperature of the hand and for anatomic or physiologic reasons, temperature gradients in the toes develop more readily than those in the fingers. Several end points have been proposed, such as nasopharyngeal temperatures greater than 35. If air is present, further deairing should occur before attempting to come off bypass. In the initial stages, after separating from bypass, additional volume can be administered by the perfusionist via the aortic cannula, usually under the direction of the surgeon or anesthesiologist. This involves taking arterial blood from the aortic cannula and passing this blood through the ultrafilter. Before this is done, both the perfusionist and the surgical team should be informed that protamine is about to be administered.

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