Peter J McDonnell, M.D.

• Director of The Wilmer Eye Institute
• Professor of Ophthalmology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0003333/peter-mcdonnell

They have extremely long microvillar rootlets that stretch into the underlying cytoplasm and may project down to the perinuclear space virus paralysis mectizan 12 mg order without prescription. Other features include the presence of glycogen and numerous vesicles in the apical cytoplasm antibiotics for dogs order generic mectizan on-line. Intermediate cells:: these spindle-shaped cells may be a transitional stage of development of basal cells to ciliated epithelial cells but are not well characterized bacteria use restriction enzymes to buy generic mectizan 3 mg online. The basement membrane provides mechanical support for cells antibiotics for klebsiella uti 3 mg mectizan fast delivery, acts as a semipermeable barrier between tissue compartments antibiotics for uti duration buy cheap mectizan 6 mg on line, and regulates cellular migration and differentiation. The combination of lamina lucida and lamina densa forms the basal lamina and both these layers are synthesized by the epithelial cells. Smooth muscle Outside the lamina propria is an almost circular layer of muscle, interrupted only by collagen and bronchial gland ducts. Smooth muscle may be seen as a thin layer when relaxed or as a thicker inner and outer layer when constricted. Thus contraction approximates the cartilage plates, causing a reduction in both diameter and length of the bronchi. Airway smooth muscle plays a pivotal role in modulating bronchomotor tone, but it may have an important role in airway inflammation and remodeling, particularly in chronic diseases. They lie outer to the smooth muscle and inside or between the cartilage, and have a gland density of approximately one gland per mm2. Intercalated ducts arise from the acini and converge to form excretory ducts, which are continuous with the airway surface. The intercalated ducts are lined by a layer of cuboidal cells, while the excretory ducts show a pseudostratified epithelium of predominantly ciliated columnar cells with intermingled goblet cells and basal cells. Normal glands are about 60% serous and 40% mucous by volume, with the serous cells more distally located in the acini. While metabolically active, they have no recognized functional significance and may represent a form of epithelial cell degeneration. Found with similar frequency in the main, upper, and lower lobe bronchi, the cells were not increased in number in chronic bronchitics, questioning the role of smoking. Submucosal glands produce a mucin-rich secretion for the conducting airways in response to neurohormonal stimuli. Gland mucus is critical in the airway defense mechanism, as it traps microbes, inhibits their replication, and clears them from the airways. It is well developed in certain species, such as rats and rabbits, in which the overlying respiratory epithelium is attenuated and flattened (called "lymphoepithelium") and is devoid of ciliated cells. This specialized epithelium is thought to allow passage of soluble and particulate antigenic material from the airways into the underlying lymphoid follicle, where it can be processed. A follicular dendritic cell network is also present and polyclonal plasma cells are identified in the perifollicular tissue. Normal alveoli are present with the center of the image being occupied by an alveolar duct. Type I pneumocytes Ninety-three to 96% of the alveolar lining is covered by type I or membranous pneumocytes. Type I cells develop from a yet unidentified fetal progenitor cell(s) and are present at birth. They form part of the extremely thin gaseous diffusion barrier between alveolar air and blood. The edges of adjacent type I pneumocytes are tightly bound together, providing an intact epithelial barrier. The cytoplasm of type I pneumocytes contains a few mitochondria, a small amount of smooth endoplasmic reticulum, and an occasional lysozyme. Micropinocytic vesicles (caveoli), which probably play a major role in transport of solutes through the cell, are seen in the plasmalemma. This tight barrier helps Acini and alveoli Terminal bronchioles constitute the most distal part of the conducting portion of the respiratory tract. The acinus lies beyond the terminal bronchiole and comprises respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli, which are all involved in gas exchange. The respiratory bronchiole is the first order of bronchiole to bear alveoli, the number of which progressively increases with subsequent branches. The respiratory bronchioles are lined by ciliated cuboidal cells and non-ciliated Club cells, although the number of ciliated cells progressively diminishes distally. At the top there is the thin attenuated cytoplasm of a type I cell with basement membrane beneath. Type I cell deep cytoplasmic extensions pass through the alveolar wall interstitium between capillaries to reach and cover parts of the opposing alveolar surface. The major function of type I pneumocytes is to allow gas exchange and fluid transport. Lung epithelium has enormous flexibility to alter the magnitude of salt and water transport. These cuboidal cells, with a diameter of 8:10 mm, have large, central, round nuclei with dispersed chromatin, prominent nucleoli and plentiful eosinophilic, vacuolated cytoplasm. The cytoplasm contains numerous mitochondria, rough endoplasmic reticulum, and many lysosomes. The characteristic feature is the presence of osmiophilic lamellar bodies, responsible for surfactant production. They also proliferate to restore the epithelium after lung injury and differentiate into type I pneumocytes. It acts in a similar way to a patch of oil on a road, so water aggregates into globules which are removed by lymphatics. Surfactant also has the important function of keeping airways open by maintaining bronchiolar patency during normal and forced respiration. When surfactant is absent, as in bronchopulmonary dysplasia, or lost, as in acute respiratory distress syndrome, small airways and alveolar walls collapse (see Chapter 3). Obstructed bronchial segment(s), an increase in lung volume, increased surface tension, hypocapnia, decreased pulmonary blood flow, and pulmonary edema may affect collateral pathways. The interstitial space is formed by extracellular matrix and a variable number of cells. Pulmonary gas exchange critically depends upon the hydration state and the thinness of the interstitial tissue layer within the alveolar-capillary barrier. The entire lung is invested with a continuous connective tissue framework from the hilum to the visceral pleura and involves the interstitial space, which contains mainly collagen and elastin fibers. This means that any force exerted on the parenchyma is distributed throughout the organ. Where the alveolar epithelium covers capillaries, the two basement membranes fuse to form a homogeneous structure. The portion of each membrane subjacent to both the alveolar and capillary endothelium is less dense and is termed the lamina lucida. In the interstitium, fluid freely moving within the fibrous extracellular matrix equilibrates with water interacting with hyaluronic acid and proteoglycans. The interstitium establishes and maintains adequate interstitial tissue fluid volume by providing a stiff three-dimensional fibrous scaffold. It functions as an efficient safety factor to oppose fluid filtration into the tissue and prevent tissue fluid accumulation. Disturbances of the deposition and/or turnover of the matrix and/or of its three-dimensional architecture and composition may evolve into pulmonary fibrosis. In pulmonary edema and lung injury, this space becomes thicker, thus impeding gaseous exchange. In acute lung injury, if edema does not resolve, interstitial pulmonary fibrosis follows. Alveolar macrophages, derived from blood monocytes, are an important component of the lung defense mechanism against inhaled particulate materials, microorganisms, and environmental toxins which escape the upper airway defense system. Alveolar macrophages vary in size from 12 to 40 mm in diameter and have a lobulated nucleus. The cytoplasm usually contains abundant particulate matter, a large proportion of which is black, due to carbon, often called anthracotic pigment. Macrophages containing phagocytosed material from cigarette smoke are often seen in the alveoli of smokers. Macrophages sequestered in the interstitium are removed by lymphatics to the draining lymph nodes. Those in alveoli mostly migrate into the upper airways, where they are removed by the mucociliary system. Besides their phagocytic role, alveolar macrophages are involved in the regulation of adaptive immune response and inflammation, including antigen presentation and the production of reactive oxygen and nitrogen species as well as metalloproteinases. They measure 10 to 15 µm in diameter and typically contain 600 to 800 nm membrane-bound intracytoplasmic granules with intra-granular inclusions of various forms. They form an immunological synapse by meeting naive lymphocytes, directing the proliferation of antigen-specific T cells and, thus, orchestrating the adaptive immune response. They integrate this information with the sensed danger signals by upregulating co-stimulatory molecules and producing specific cytokines. Only a few lymphocytes are normally found in the alveolar interstitium, as they become progressively less in number distal to the bronchioles. Neutrophils and eosinophils are normally present in small numbers in the walls of the conducting airways but rarely in the alveolar interstitium. The megakaryocytes may be intact with multilobed, hyperchromatic nuclei and abundant cytoplasm, but are more often seen as naked or semi-naked hyperchromatic nuclei. Pulmonary vasculature As already discussed, pulmonary arteries return deoxygenated blood to the lungs, whereas bronchial arteries supply oxygenated blood to maintain the pulmonary tissues. Megakaryocytes derived from the bone marrow are fragmented into platelets in the pulmonary circulation. As are all systemic arteries, the pulmonary arteries are composed of three layers, the intima, media, and the adventitia. However, the pulmonary circulation is a low-pressure system (with the normal mean pressure of approximately 10 mmHg) and the structure of the blood vessels somewhat differs from other systemic arteries. The pulmonary arteries run alongside the airways and the diameters of the pulmonary artery and the accompanying airway are roughly equal in cross section. The elastic pulmonary arteries are thin-walled, as the media contains predominantly elastic fiber lamellae and relatively little smooth muscle. In adults, elastic fiber lamellae are less compact and more irregular and fragmented as compared to infants. Pulmonary vessels should never be assessed for their medial thickness on H&E sections alone. Muscular pulmonary artery, which becomes progressively smaller, with eventual loss of the media and fusion of the elastic layers. Internal and external elastic laminae are present in the muscular pulmonary arteries and extend to the arterioles. This is the result of progressive attenuation of the medial smooth muscle, up to a point where a single fragmented elastic lamina is all that separates the intima from the adventitia. A rapidly emerging concept is that the vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. In response to stress or injury, resident adventitial cells can be activated and reprogrammed to exhibit different functional and structural behaviors. Functions include proliferation, differentiation, upregulation of contractile and extracellular matrix proteins, release of factors directly affecting medial smooth muscle cell tone and growth, as well as stimulating recruitment of inflammatory and progenitor cells to the vessel wall. Each of these changes in fibroblast phenotype directly or indirectly modulates changes in overall vascular function and structure. In response to vascular stresses, such as overdistension and hypoxia, the adventitial fibroblast is activated and undergoes phenotypic changes. Some believe the adventitia is the seat of vascular progenitor cells, capable of differentiating into endothelium or smooth muscle cells. The capillaries are 7 to 10 mm in diameter and the partial pressure of the alveolar gases controls the amount of blood flowing into them. Pulmonary capillaries are lined by continuous endothelial cells of a non-fenestrated type. Pulmonary capillary endothelial cells, which are also termed microvascular endothelial cells,267 show a higher constitutive expression of adhesion molecules compared to systemic capillaries. These may contribute to the sequestration of a large intravascular pool of neutrophils in the lung. These cells contain large numbers of caveolae and show long cytoplasmic extensions, which encircle much of the vessel. The cytoplasm contains mitochondria, free ribosomes, rough endoplasmic reticulum, and Weibel-Palade bodies. Pericytes (Roget cells) are closely applied to the outer walls of alveolar capillaries and probably have a contractile function. Their branched cytoplasmic processes are partially embedded in endothelial basement membrane and contain fine filaments similar to those seen in smooth muscle cells. They are located in interlobar connective tissue septa, as opposed to the pulmonary arteries, which lie with airways within pulmonary lobules. The bronchial arteries run parallel to the airways within the bronchovascular sheath. Bronchial arteries can also be distinguished from pulmonary arteries by a single thick internal elastic lamina and a poorly formed, if at all visible, outer elastica. Some have prominent intimal longitudinal muscle, which is not present in the newborn but develops by 3 months, due to stretch. The visceral pleura also contains a welldefined elastic lamina in the submesothelial connective tissue, which is an important layer, since the presence of tumor below or above it contributes to the staging of pulmonary epithelial tumors. These cells may be either flat or cuboidal depending upon their metabolic activity and site. Ultrastructurally, mesothelial cells are characterized by long forked microvilli measuring up to 3 µm in length and 0.

Larger pleural specimens should be carefully examined for peripheral adherent lung and skeletal muscle infection 4 weeks after miscarriage generic mectizan 3 mg with mastercard. The number of sections should correlate with the index of suspicion for malignancy script virus order mectizan on line amex. It is easy to appreciate both the main tumor mass and the gross involvement of lymph nodes when the specimen is cut along the airway antibiotics for acne yahoo mectizan 3 mg buy free shipping. The distance from the bronchial or medial resection margin is also more easily noted antimicrobial plastic discount mectizan 3 mg amex. Depending on the indication infection 4 weeks after miscarriage buy mectizan mastercard, larger specimens may be sent to the pathology laboratory for processing. Receipt of these larger samples is typically viewed with relief by both general and expert pathologists. They both understand that with pleural biopsies, larger biopsies usually result in a higher level of diagnostic confidence. This is particularly true when a thoughtful surgeon, an attentive pulmonologist, and an astute radiologist contribute to the evaluation. Benign and malignant pleural diseases are covered in depth in Chapter 36 and therefore only a few basic principles of processing are warranted. When the pleural space is open and there is diffuse nodular disease, the surgeon will have a wider range of options for biopsy sites. It is preferable to include at least one wedge biopsy of the lung that will help to define the visceral pleural pathology in relationship to the underlying lung. In addition multiple biopsies from the parietal pleura, chest wall, mediastinum, and diaphragm should be taken. When the pleural space is partially or completely obliterated, the surgeon will face greater technical difficulty in assessing the pleural disease (diffuse pleural fibrosis versus malignancy) and obtaining the appropriate use of ancillary studies must be grounded in a well-formulated differential diagnosis and correlated with morphology. The clinician and the radiologist contribute greatly by providing a complete and accurate history, which helps the diagnostic work-up and avoids unnecessary tests. In some areas, such as interstitial pulmonary fibrosis, a combined diagnostic approach in a joint meeting is the only rational way to achieve the correct diagnosis. A general overview is provided here; more specific indications for these ancillary tests are covered in subsequent chapters. Despite a great deal of technological innovation and enthusiasm for molecular testing, histochemical stains remain a mainstay in the diagnosis of neoplastic and non-neoplastic lung disease. Histochemical stains have the great virtues of rapid turnaround time, low cost, technical simplicity, and applicability to standard cytology and histology samples. Histochemical stains can be divided into those routinely performed to detect microorganisms (Grocott methenamine silver, Ziehl-Neelsen, Gram), those staining matrix substances (Masson trichrome, Movat pentachrome, elastic van Giesen, and Congo red), those that demonstrate intracellular mucin (mucicarmine, periodic acid-Schiff), and those detecting other substances, such as iron or calcium. Immunohistochemistry has also been applied to the diagnosis of mycobacterial, fungal, viral, and bacterial infections. Immunohistochemistry in pulmonary pathology has been extended into prognostic markers and therapeutic response predictors. The technique is based on a primary antigen-antibody reaction and a secondary antibody-enzyme complex, which interacts with a chromogen for a microscopically visible color reaction. Immunohistochemistry can be performed on either frozen or 49 Chapter 2: Lung specimen handling and practical considerations formalin-fixed tissue, depending on the antibody. It is good practice not to use a tissue block that contains previously frozen material for immunohistochemistry, if other tissue blocks are available. Unfortunately, there are very few antibodies which approach 100% sensitivity and specificity. As immunohistochemical experts emphasize, it is diagnostically irrelevant to speak of overall sensitivity and specificity for a particular antibody. Rather it is more appropriate to speak of relative sensitivity and specificity within a particular differential diagnosis. This requires clinical interaction and morphological expertise in generating a differential diagnosis, in addition to critical assessment of the immunohistochemical results with appropriate controls (see Chapter 26). Immunohistochemistry is often used in the work-up of lung and pleural tumors, either to better characterize the primary or to exclude metastatic disease. It is vital to understand the staining patterns of the normal lung and pleura, particularly in a small or distorted specimen. For example, cytokeratin antibodies will stain benign bronchial and alveolar epithelia, as well as reactive mesothelial cells, which can be entrapped within tumors and lead to a false positive interpretation. The histopathologist must be aware of the staining for a particular monoclonal antibody in tumors in the differential diagnosis. Thus calretinin, while positive in some epithelioid mesotheliomas, may stain the nuclei of some sarcomatoid carcinomas (see Chapter 36). In individual cases, immunohistochemical analysis remains an exercise in probabilities and may not be sufficient for certain clinical circumstances. New markers are often introduced with initial published reports of high sensitivities and specificities. After additional studies and incorporation into daily practice, more exceptions appear. There is no substitute for a good clinical history, thorough physical examination, high-quality radiology, and pathology evaluation based on routine hematoxylin and eosin-stained sections. The diagnosis of epithelioid mesothelioma is satisfactorily confirmed with an immunohistochemical panel in most cases. Electron microscopy, if available, can be reserved for the occasional instances in which the immunohistochemical profile is equivocal. Prompt fixation in a recommended fixative (glutaraldehyde or methanol-free formaldehyde) is preferred, although commercial formalin may be used if the fixation is rapid. A new sharp blade should be used and cut with a to-and-fro motion, rather than by exerting downward pressure. Other selected uses in non-neoplastic disease include the demonstration of electron-dense deposits. New molecular techniques for the evaluation of neoplastic and infectious diseases have been introduced into the pathology laboratory, although the degree to which these techniques have been incorporated into clinical practice varies worldwide. In some centers, molecular testing is not only being used in diagnosis, but also to address prognosis and to assess therapeutic targets. The potential applications for immunohistochemistry and in situ hybridization have been similarly expanded. Fewer studies address the cost-benefit analysis associated with new assay validation and implementation into the clinical laboratory. Another issue that must be addressed within the clinical laboratory and in collaboration with clinical colleagues is what to test. The new molecular technologies can be applied to a bewildering array of different fresh biological samples, including tissue, aspirates, effusion fluid, and bronchial specimens. Although not an insurmountable obstacle for some assays, formalin fixation and paraffin embedding can impair nucleic acid retrieval. It is also more difficult to control the prevailing environmental conditions of paraffin block storage and histological processing. When adopting a new molecular assay, the clinical pathology laboratory faces the additional challenge of deciding who should perform and interpret the test. Atelectasis/overinflation Atelectasis is a frequent finding in all types of lung biopsies and could lead to mistakes in diagnosis. This can be avoided through proper fixation and careful comparison with other areas in the biopsy. If not certain, a trichrome stain may clearly show delicate thin alveolar septa, as opposed to definitive interstitial fibrosis. In open lung biopsies, various distension techniques have been proposed to prevent artifactual atelectasis. Overinflation of lung tissues could occur by direct instillation of cryomatrix into a non-formalin-fixed lung. As a consequence, dilated alveoli could be misdiagnosed as emphysema or lymphangiectasia. Artifacts in biopsy Under ideal circumstances, a properly obtained representative sample of lung should provide useful diagnostic information. An iron stain highlights hemosiderin in macrophages as clumpy, dark-blue material. Caution is advised since the finely pigmented golden brown and carbonaceous intracytoplasmic material seen in macrophages from cigarette smokers can resemble hemosiderin. Prominent areas of atelectasis are frequently present in transbronchial and open lung biopsies. In this tranbronchial biopsy, the sharp interface of normal lung adjacent to collapsed lung is helpful in identifying atelectasis, as opposed to a fibrosing disorder. Commonly seen in transbronchial and open lung biopsies, intra-alveolar hemorrhage results from the filling of the alveolar spaces with fresh blood during the biopsy procedure. The intra-alveolar hemorrhage is associated with hemosiderin-laden macrophages, which indicates that there had been past episodes of bleeding. The coarse brown granules of hemosiderin in intra-alveolar macrophages in the left panel should be distinguished from the finely pigmented golden brown and carbonaceous intra-cytoplasmic material seen in macrophages from cigarette smokers in the right panel. Crush artifact Crush artifact is frequently seen in the setting of small cell carcinoma, but may be seen in benign and malignant lymphoproliferative disorders. Biopsy forceps can crush any tumor beyond histological recognition but small cell carcinoma and lymphoid lesions are prone to distortion. Other areas of this particular tumor demonstrated obvious small cell carcinoma morphology. Bubble artifact this is a common finding in lung biopsies due to crushed or collapsed airspaces and has been referred to as "pseudolipoid pneumonia". In some cases of recent massive alveolar hemorrhage, hemosiderin-laden macrophages may be absent, rendering clinical correlation a necessity. The center panel illustrates "barb-like" prongs of the foam material, viewed microscopically. In the tissues, triangular, irregular shapes are due to intrusions of the foam material in the right panel. This consists of irregularly shaped round-to-slightly oval spaces within the lung parenchyma, without evidence of a foreign-body giant cell, fibrinous material, or an inflammatory response. Incidental lesions A large number of nonspecific lesions may often be identified in all types of lung specimens. They can occur in various locations, including the airways, lung parenchyma, vasculature, or other sites (Table 2). While some are of no pathological consequence, Large airways Ossification of tracheobronchial cartilage With aging, calcification and ossification of cartilage are common in large airways and are not usually of pathological consequence. Samples from older individuals often demonstrate oncocytic change in seromucinous acini. It may be difficult in limited samples to separate localized scarring from a diffuse interstitial pneumonitis. Careful scrutiny of subjacent lung parenchyma is essential as well as clinical and radiographic correlations. Bone marrow cellular elements may be readily identified in the ossified cartilage. In lung allograft patients prominent ossification, calcification, and fibrovascular ingrowth of bronchial cartilage have been noted, possibly related to ischemic change. There is dense basophilic fibrosis with replacement of the pulmonary parenchyma with abundant eosinophilic collagen. Prominent stromal elastosis may be present in some cases and this is best appreciated on elastic and trichrome stains. Oncocytic metaplasia of bronchial submucosal glands the bronchial submucosal glands may show pronounced oncocytic changes with advanced age. Some asthmatic patients may show changes in the extracellular matrix that lead to elastosis and elastic fiber fragmentation in large airways. Parenchymal Scar Scarification in the lung is fairly common and increases with aging. A localized pulmonary scar is usually found in the periphery of the lung with essentially unremarkable lung underneath the zone of fibrosis. They should be differentiated from other smooth muscle proliferations in the lung such as "benign metastasizing leiomyoma", primary pulmonary leiomyoma/leiomyosarcoma, and lymphangioleiomyomatosis (see Chapter 33). Small foci of smooth muscle hyperplasia predominantly involve the pulmonary interstitium. The central panel shows a distinctive spiculated or star-shaped structure, known as an asteroid body. Pale, irregularly shaped or block-like structures signify calcium oxylate crystals in the right panel. This was first described in asbestosis, but is a nonspecific finding in diverse non-neoplastic lung disorders. Some authors postulate that the bodies form by sequential aggregation, fusion, and coalescence of degenerated alveolar macrophages,46 while others suggest a localized reaction to foreign material. Corpora amylacea have no particular diagnostic importance, except that principal differential diagnostic considerations include distinction from inhaled or aspirated exogenous material, fungal forms, or pulmonary alveolar microlithiasis. Blue bodies Blue bodies are intra-alveolar laminated basophilic concretions of an uncertain etiology. Electron microscopic studies have demonstrated calcium carbonate and other inorganic substances. These inclusions could falsely lead the pathologist to conclude the granulomas are of a foreign body type. Often the granulomas are associated with birefringent crystals within giant cells and macrophages. One can find poorly stained, lucent materials within or surrounded by giant cells in over two-thirds of open lung bodies in sarcoidosis. Senile amyloid Focal deposits of amyloid occur commonly in the lung and other organs in elderly patients as a frequent incidental finding without evidence of other forms of amyloidosis. Although they are periodic acid-Schiff positive, one should not confuse them with fungi.

The cervix is pulled upwards and forwards antibiotic valinomycin cheap mectizan 12 mg line, placing the uterosacral ligaments on the stretch antibiotic viral infection buy cheap mectizan 12 mg line. The vaginal flaps that have been dissected from the cervix are drawn posterolaterally antibiotic used to treat bv buy discount mectizan online. For instance antibiotics for uti types 12 mg mectizan buy free shipping, the cardinal ligament and the uterine pedicle may require three clamps and separate sutures for their safe and secure ligation bacteria used for bioremediation mectizan 3 mg with mastercard. First one side and then the other is dealt with so that the surgeon ligates both uterine vessels before proceeding higher. This increases the degree of uterine mobility simultaneously and to a greater degree than if one side is completely transected before the other is detached. The tip of the clamp securing the uterine pedicle should include the peritoneum on the anterior and posterior surface of the broad ligament. This reduces the chances of a vascular tributary not being included in the ligature. At this stage, if not yet done, the peritoneum of the uterovesical pouch should be opened by introducing a finger into it from the already opened pouch of Douglas. When only the ovarian ligament and round ligament are attached to the uterus on each side, the uterine fundus can usually be exteriorised by passing it posteriorly through the pouch of Douglas. Once the uterus is delivered, the ovarian pedicles and the round ligaments are clamped either together or separately and the uterus removed. The ovarian and round ligament pedicles are then doubly ligated and one ligature is left long as a marker. The Peritoneal Sac and Closure of the Uterosacral Hiatus: Some surgeons close the peritoneum completely in order to extraperitonealise the location of the pedicles. Complete closure of the peritoneum is not necessary, however the process of extraperitonealising the pedicles has been described later. Any redundant peritoneum of the pouch of Douglas should be excised to reduce the risk of enterocoele formation. The posterior cut edge of the peritoneum, adjacent to the initial vaginal incision in the posterior fornix, is picked up and the peritoneum carefully dissected by sharp and blunt dissection as far as the rectum. The remaining ligatures attached to the two uterosacral ligaments are then picked up and, using an empty needle, the ligatures are passed through the posterior peritoneum and tied together, approximating the uterosacrals and obliterating the potential hernial sac. The ligatures can then be passed out on an empty needle through the posterior vaginal tissue and left long, held on a clip. When there is a small cystocoele, the bladder is dissected from its lateral attachments to the vaginal fascia of the anterior the Uterus vaginal flaps until a firm pillar of pubovesical fascia is reached (see earlier). This pubovesical fascia is united in the midline by interrupted sutures from the urethral meatus to the peritoneum of the uterovesical pouch. The last of these sutures secures a good bite of pubovesical fascia laterally, and includes the peritoneum of the uterovesical pouch. When tied, it closes the anterior part of the hiatus through which the uterus has been removed. Some gynaecologists leave the second ligature of each remaining pedicle long in order to thread them through an empty needle and bring them through the adjacent vaginal wall. The long sutures from the previously united cardinal ligaments are fixed in the posterior fornix and those from the round ligament to each lateral fornix. The theory is to help obliterate dead space in which haematoma formation can occur and possibly as a prophylactic against subsequent vault prolapse and enterocoele. Additional Uterosacral Sutures if Needed: If there is a significant gap between the cut edges of the uterosacral ligaments, the posterior peritoneum and the posterior vaginal wall, extra-peritoneal uterosacral sutures can be employed to close this shelf. If a severe degree of prolapse is present, the uterosacral ligaments and their downward prolongations may be ill-defined and identified with difficulty. The cervix is being drawn upwards and to the left while the surgeon hooks an index finger around the remaining pedicle before applying a clamp. The fundus of the uterus has been displaced posteriorly through the incision in the pouch of Douglas. Once the excess vaginal tissue has been excised, the vault can be closed using a No. This closure can be performed either longitudinally or transversely, depending on the degree of prolapse and the direction of the vaginal incisions required at the start of the operation. In this, the uterine fundus is delivered through the anterior (uterovesical) pouch. The Ovarian, Round Ligament and Uterine Pedicles: the uterus is grasped with uterus-holding forceps. Hysterectomy clamps, such as Zeppelin or Rogers, are now placed over the Fallopian tube, ovarian ligament and round ligament on the left. The anterior peritoneal flap has been closed by a reefing suture that passes from one round ligament to the other. The sutures from the ovarian pedicles have been left long in this image, although they can be cut shorter when haemostasis has been confirmed prior to closure. The edge of the peritoneum is illustrated diagramatically; the two uterosacral ligaments A and B can be approximated and the sutures brought out through the posterior vaginal wall. This practice is not advocated by the authors however, as it applies unnecessary tension to this important vascular pedicle, risking haemorrhage. The round ligament pedicles should also not be approximated to avoid tenting the vaginal vault. The clamp should be closed firmly, after which the tissue intervening between the clamp and the uterus is cut through on the uterine side. Alternative method, where the fundus of the uterus is pulled down through the uterovesical pouch. The posterior repair is completed as in Chapter 14, if this proves to be necessary. The fundus of the uterus is drawn over to one side and, with curved clamps, the ovarian ligament, Fallopian tube and the round ligament are clamped. The operation can be continued down towards the uterine vessels, which can be clamped, cut and ligated much like it were an abdominal hysterectomy. Opening and Excising the Redundant Pouch of Douglas: At this stage of the operation, the fundus of the uterus should be pulled downwards and towards the surgeon. The pouch of Douglas is then exposed from within the peritoneal cavity, easily exposing any hernia of the pouch. The visualisation can be made easier by everting the pouch of Douglas with a finger placed in the posterior fornix. If a hernia is present, the peritoneum on the posterior surface of the hernial sac is cut through transversely, and the hernial sac stripped away from its posterior attachments until the level of the rectum has been reached. The posterior leaf of peritoneum can be held by a stay suture or a pair of long forceps. Following division, the uterosacral ligaments may be sutured together (McCall culdoplasty). As the two structures meet in the midline, they help to close off the pouch of Douglas and prevent enterocoele formation. If there is any clinical doubt, an ultrasound scan can confirm the uterine size and exclude any tubal or ovarian pathology. A uterine sound can be passed to help confirm the uterine size, and if additional pathology such as adhesions or endometriosis is suspected, a diagnostic laparoscopy carried out. Circumcision of the Cervix: Using a scalpel, a circumferential incision is made around the cervix at the junction between the cervix and the vagina. Identification and Opening of Pouch of Douglas: In the absence of prolapse, the most straight-forward entry into the peritoneal cavity is often through a posterior colpotomy. Opening the pouch of Douglas at this stage in the operation enables the uterosacral ligaments to be secured. The tissues contained in the clamps have been cut through on the uterine side of the clamps, and the uterus is drawn downwards. If the posterior fornix has not been opened, the fundus of the uterus is drawn downwards and backwards. Two fingers of the left hand can be placed posteriorly, in the posterior fornix and between the uterosacral ligaments, thus elevating the posterior peritoneum of the pouch of Douglas. The upper limit of the peritoneal sac is exposed and the peritoneum divided at the base of the sac along the dotted line. The posterior vaginal wall should be dissected away from the tissues lying on the back of the cervix, and in due course the peritoneum of the pouch of Douglas will be identified. Care must be taken to avoid separating the peritoneum from the back of the uterus. The position of the pouch of Douglas can often be identified by a shallow depression between the two uterosacral ligaments, which is accentuated when the cervix is drawn upwards and forwards. The apex of the peritoneum of the pouch is often further away from the cervix than expected, and the tendency is to make the initial scissor cut too high and miss the peritoneum altogether. It is then necessary to make progressively lower snips until the glistening peritoneal membrane is found. A small gush of free fluid is an additional reassuring proof that the peritoneal cavity has been entered. Mobilisation of the Bladder: the next stage is to divide the vesicocervical ligament and expose the vesicocervical space. This part of the operation is more hazardous when the cervix cannot be pulled downwards, as there is a greater risk of injury to the bladder. It may be easier to make a small midline incision in the anterior vaginal wall extending towards the urethral meatus for about 3 cm from the circular incision. Identification of the Uterosacral Ligaments: the cervix is now pulled laterally and a little upwards to expose the side of the cervix. This exposes the downward prolongation of the cardinal ligament, together with the lower extremity of the uterosacral ligament. These structures are then divided, and at each step further descent of the uterus occurs. One helpful technique in the absence of prolapse is to use an aneurysm needle threaded with heavy suture material to ligate each structure in turn. The tissues are then doubly ligated after clamping and separation from the uterus with scissors. The cut edge of the divided tissues is inspected for haemorrhage, and if the haemorrhage has been completely controlled the ends of the ligatures are preserved for fixation to the vault. If possible, each succeeding second ligature should encircle the previous pedicle to eliminate bleeding from any vessel between the two. The Uterine Pedicles: Prior to ligation and division of the uterine vessels, it is essential to ensure that the ureter is well away from the surgical field. If the bladder pillar has been correctly divided, both the bladder and the ureter can be pushed well away from the region of the uterine vessel. Again, a suture passed through an aneurysm needle can be used to ligate the parametrium and uterine vessels prior to clamping and division of the pedicle. It is vital to ensure that the tip of the clamp includes the peritoneum of the broad ligament at both the front and the back. The parametrium is divided close to the uterus medial to the clamp with either scissors or a scalpel. Great care should therefore be taken when placing clamps and ligatures as there is a risk that the uterine vessels can retract upwards away from either the clamp or the ligature. This is less likely to happen if a small cuff of tissue is left distal to the clamp. Ligature of the cardinal ligament using a modified aneurysm needle (after Gwillim). Delivery of the Uterus: At this stage of the operation, the fundus of the uterus can often be drawn through the pouch of Douglas. The attachments of the round ligament, the Fallopian tube and the ovarian ligament to the uterus are now taken in a hysterectomy clamp and separated from the uterus after being doubly ligated with a heavy suture. Closure of the Peritoneal Cavity and Vagina: the long sutures of the uterosacral ligaments can then be tied with an empty needle to the posterior peritoneum and the posterolateral vaginal walls or vaginal angles, and the anterior and posterior incised edges of the vault closed transversely with a continuous suture in a similar fashion to that described above. It is important to include the posterior peritoneal surface with the vaginal vault suture to minimise the risk of bleeding vessels between the two cut edges. Previously, the anterior uterovesical peritoneum was approximated to the posterior peritoneal edge and the vaginal vault, although this is now less common practice. Oophorectomy at Vaginal Hysterectomy Proponents of laparoscopic and abdominal surgery will often site the need for concurrent oophorectomy as a contraindication to the vaginal route for hysterectomy. The uterine vessels are being encircled by a ligature introduced with an aneurysm needle. Application of clamp prior to incision and insertion of second ligature by suture. Oophorectomy is more easily achievable in the context of patients with uterine descent and an adequate introitus. In cases with limited vaginal access or no uterine descent, oophorectomy has been described using transvaginal endoscopic oophorectomy,63 or by performing a laparoscopic-assisted vaginal hysterectomy, where the ovaries are taken first, prior to the vaginal component of the operation. Heaney forceps) is used to clamp the infundibulopelvic ligament as close to the ovary as possible. The Fallopian tube and ovary can then be removed and the pedicle double-tied with a No. Care must be taken for the ureter, the Uterus which runs along the pelvic-sidewall posterior to the infundibulopelvic vessels. As described by Sheth, it may is beneficial to divide the round ligament and ovarian ligament on one side first, keeping a long tie on these pedicles, before taking the contralateral round ligament and then the infundibulopelvic ligament, using the vulsella on the uterus for traction to bring the pedicle towards the surgeon. This allows the uterus and one tube and ovary to be removed, and allows space to then proceed with taking the infundibulopelvic ligament of the remaining tube and ovary to complete the operation. The fibroids can then be grasped with a Vulsellum forceps or Littlewoods forceps, and removed with sharp or blunt dissection and traction. Great care must be taken to protect adjacent structures, such as the vaginal walls, the bladder, the rectum and the small bowel. This is achieved with the help of lateral wall vaginal retractors, a Sims speculum and a small degree of head-down tilt. Laparoscopic supracervical (sub-total) hysterectomy, with or without coring of the endocervical canal.

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The cause and nature of adhesion formation in an individual case must be a matter for speculation antibiotics prior to surgery discount mectizan. It is logical to conclude that failure of haemostasis and trauma to peritoneal surfaces must play an important part bacteria in florida waters mectizan 3 mg on line. However antibiotics zone of inhibition cheap mectizan 6 mg amex, the regenerative powers of the peritoneum are considerable and those who have occasion to reopen the abdomen after a major operation in which the pelvic peritoneum has largely been denuded will be amazed to find how a glistening surface has regenerated over what was formerly a bare area and though there will be adhesions they are not usually as extensive as one might otherwise suspect bacteria have 80s ribosomes buy 12 mg mectizan with amex. Relatively minor procedures in other individuals antibiotics for uti female generic mectizan 3 mg buy online, however, appear to be followed by massive adhesion formation. In such patients, when surgical procedures are undertaken for infertility every possible measure to reduce the subsequent reformation of these must be taken. Adhesions binding down the uterine tube or ovary must be put on the stretch and divided individually and in a painstaking manner with the microdiathermy electrode. Surface adhesions over the ovary are very likely to interfere with release of the oocyte at ovulation and indeed in some patients this phenomenon presents as recurrent ovarian cyst formation. Consideration should be given to the use of intraperitoneal anti-adhesion substances. Surgery can be undertaken laparoscopically or via laparotomy depending on the patient history and surgical expertise. Salpingostomy or tubal occlusion are regarded as easier to perform in cases of severe adhesions,78 with reduced side effects and quicker patient recovery times. Most tubal surgery is now carried out laparoscopically, but the principles are similar to conventional open surgery. Hence some descriptions of open surgery have been retained here, but in less detail than in former editions. Genuine hydrosalpinx formation is more likely to be due to an intrinsic inflammatory condition of the oviduct and often implies a greater degree of damage to the physiology of the tube than is apparent with the naked eye. In this instance the transfundal injection of saline not only confirms cornual patency but also, by distending the hydrosalpinx, displays a scarred, dimpled area caused by fimbrial invagination. This area is then carefully incised with a fine diathermy point and the opening is slowly and carefully enlarged by incising along avascular planes from within outwards to display the buried fimbrial remnants. Often, however they remain conglutinated, and a large number of sutures are needed to evert the fimbriae (fimbriolysis). In this technique the opened mucosal layer of the tube is everted and rolled back, even further than with fimbriolysis, over the serosa to which it is secured by fine sutures. The pregnancy rate after this latter operation is very disappointing, and there is an enhanced risk of ectopic pregnancy. A cuff of distal tube is turned back and sutured so that the external ostium is permanently exerted. An injection of coloured uid through the fundus will demonstrate patency of the proximal tubal stump if the cervix is occluded. The conglutinated mbriae are stitched back to the tubal serosa by ne everting sutures. Originally this operation was carried out by open laparotomy, the surgeon often using loupes to give some magnification. Microsurgery was found to increase the success rate, but laparoscopic reversal has been found to be quicker, result in shorter hospital stay and achieve similar pregnancy rates as the former. Success is dependent upon the length of the tube following anastomosis, and if this is less than 4. The vast majority of sterilisation operations are now carried out using clips or rings, with minimal loss of tubal length, and there is no place for ampullary-isthmic anastomosis. The two ends of the tube are then brought together along with the mesosalpinx and a series of very fine non-absorbable sutures used to approximate the ends. The latter does not usually present major difficulty but adequate mobilisation is essential to avoid tension and before the tubal anastomosis is carried out a suture approximating the mesosalpinx should be placed, which will eliminate inadvertent and inappropriate tension being applied to the tubal sutures during their placement. Isthmic bevel: A technique precisely similar to that used in intestinal anastomosis between loops of disparate size, may be effective. A small slit is made in the anti-mesenteric border of the isthmic portion of the uterine tube. The Fallopian Tube the muscle walls are of unequal thickness, the bite of suture taken should be the same in both segments of tube but in the thicker segment not all the myosalpinx should be included but only that portion nearest to the lumen so that the anastomosis ends up with symmetrical distance of suture bite between the lumen of either segment. If, however, the proximal part of the ampullary segment is fibrosed or diseased, then this requires serial section until healthy tube is exposed. It is this situation which leads to the disparity in lumen for which the management outlined above is indicated. The occluded cornu is then sliced as a thin disc (approximately 1 mm thickness) until such time as the pent-up fluid within the uterus spurts forth from the severed end of the patent intramural tube. All further scar tissue must be carefully trimmed under high magnification and haemostasis achieved with bipolar diathermy. The next stage is to thread a number one nylon suture or the equivalent carefully and gently into the cornual ostium. The hollow ended probe is used to thread the other end of this temporary splint through the distal segment of tube for anastomosis. The anastomosis commences with sub-mucosal muscular sutures usually 8/9 gauge, with the knots tied externally. The first such suture should be placed on the side of the anastomosis furthest from the operator. It may, however, be an advantage to place a suture in the mesosalpinx in order to bring the two segments for anastomosis into apposition. Very gentle stretching of the lumen of the tube to be attached using fine jewellers forceps may make the edge more readily defined for the accurate placement of sutures. The remaining steps of the procedure are not materially different from previously described tubo-tubal anastomosis. The splint is removed at the end of the procedure and a further injection may confirm that a waterproof patent anastomosis has been achieved. Sterilisation procedures, particularly diathermy, which have been carried out on the isthmic portion of the oviduct may produce the same result. In either instance the most proximal part of the interstitial oviduct may have escaped the occlusive effect of trauma or inflammation. The presence of such a small patent segment may only be determined by preliminary hysterosalpingography or possibly hysteroscopy. The operation of uterotubal implantation has now been abandoned, as results were so poor, and it has been replaced by microsurgical tubo-cornual anastomosis. Infection can completely vitiate any benefits from such surgery and peri-operative antibiotic therapy is recommended. Retrograde dye pertubation with either a very dilute methylene blue solution or clear normal saline is used. A ree ng effect on the serosa is produced, which absorbs the discrepancy (after Gomel). Coitus: After straightforward tubal anastomosis, unprotected intercourse may be permitted in the cycle after the first menstrual period following operation. Pregnancy: It is safest to suspect ectopic pregnancy whenever gestation occurs following tubal restorative surgery. Subsequent viable pregnancy: Vaginal delivery should be ordinarily entirely satisfactory for all cases except those in which the myometrium has been transgressed. Subsequent persistent infertility: If pregnancy has not ensued after 12 months, it is reasonable to perform a hysterosalpingogram to assess the operative result. If, however, there is partial or complete occlusion of the Fallopian tube, leading to a degree of hydrosalpinx, either fimbrioplasty or salpingostomy will be required. Fimbrioplasty this operation is required when there is fimbrial conglutination, resulting in phimosis of the distal end of the tube, but usually there is some degree of patency. Once all the adhesions are divided and the tube is as free as possible, it is grasped with atraumatic forceps to expose the distal end. A pair of alligator-tipped forceps is introduced into the small tubal ostium and opened and closed gently to break down adhesions and widen the ostium. The same procedure is then carried out with the instrument at right angles, and the tube will fall open and remain open without the need for suturing. The surgeon needs to be thoroughly trained and experienced, and a good assistant is essential. The principles of laparoscopic surgery for tubal infertility are similar to those for tubal microsurgery and almost all the operations described above may be done laparoscopically provided adhesions are not too dense. The patient is placed in the standard laparoscopic surgery position and a cannula is inserted through the cervix into the uterine cavity. An exploratory laparoscopy is first carried out to assess the extent of adhesions and severity of tubal disease. Three suprapubic trocars will be required in most cases and methylene blue dye is injected into the uterine cannula to check whether there is any tubal filling and/or patency. Once a thorough inspection has been carried out, the surgeon assesses whether it will be feasible to proceed with the operation, and which of the techniques of tubal surgery will be required. Salpingostomy If the fimbrial end is completely occluded, it is likely that the tube will be distended as a hydrosalpinx. The size of this may be exaggerated by the methylene blue dye which has been instilled. If the tubal wall is very thickened, it is likely that the epithelium is so badly damaged that the operative results will be poor. Similarly, a very large thin walled tense hydrosalpinx is likely to have such poor tubal epithelium that success in terms of pregnancy is unlikely. In very severe cases, provided there has been prior discussion with the patient, it may be best to remove a large hydrosalpinx, leaving the pelvis in an appropriate situation for in vitro fertilisation. If, however, the surgeon considers that the degree of dilatation of the tube is not too gross, the distal end is grasped and a small incision made into the dimple at the apex of the tube. This may be made with a diathermy needle, or with scissors, and two or three more incisions are made over avascular lines, each incision being 1­2 cm in length. Eversion of the new opening is maintained by touching the serosal surface of the tube just proximal to the new opening with either bipolar coagulation or with a diathermy probe. Laparoscopic Adhesiolysis It will often be necessary to carry out adhesiolysis before the tubes and ovaries can be inspected. Adhesions may be divided with laparoscopic scissors, diathermy hook or needle electrode, or with laser. The division of adhesions should commence with those in the midline, gradually working laterally. Adhesions should be put on the stretch, by using grasping forceps and the line of division should be as close to the affected organ as possible, and particular care should be taken with adhesions involving small or large intestine, to avoid electrical injury to the bowel wall. Once the pelvic anatomy has been restored, it may be found that the Fallopian tubes are patent and that the ovary and tube are now Tubal Anastomosis this procedure is usually performed for reversal of sterilisation. The procedure followed is very similar to its laparotomy counterpart, with the occluded part of the tube being excised using fine scissors until a fresh vascular tubal lumen is identified on each side of the occluded portion. The ends of the tube are now anastomosed, using fine absorbable sutures such as 6/0 polyglactin. It is not usually necessary to insert more than four sutures in all but the operating time is considerable in using such fine sutures with intracorporeal knot tying. Some surgeons will only anastomose one tube because of the length of operating time. Using microsurgical techniques, Margara has reported a 60% overall pregnancy rate,81 but in optimal cases where good tubal length was available, rates as high as 80­90% have been claimed. Laparoscopic reversal of sterilisation has not yet achieved these high pregnancy rates. However, in specialised centres, figures of 25% are quoted provided the hydrosalpinx was not thick walled and excessively dilated. Although numbers are not large, several studies of laparoscopic salpingostomy demonstrate a pregnancy rate of 30% and above, and similar good results have been claimed for laparoscopic fimbrioplasty. However, it must not be forgotten that there is also a considerable incidence of ectopic pregnancy following all of these surgical methods. Current reviews are still inconclusive and more studies with the appropriate statistical power and elimination of confounding factors are required. The use of embryos for research, the potential for genetic manipulation and the fate of unused frozen embryos are some of the major issues. In addition, there are social ethical issues around the use of donated ova to post-menopausal women, the application of these techniques to single women, and the request for frozen embryos to be re-implanted after the death of one or other of the parents. In most countries, there are statutory licensing bodies that monitor the activities of assisted reproduction units and impose codes of practice that are variably regulated by law. Many centres find it useful to have an Ethics Committee, with wide representation from different religious, cultural and professional backgrounds to advise on both research and clinical practice. Variants of in vitro fertilisation were developed over the next few years such as gamete intra-Fallopian transfer, ovum donation, intracytoplasmic sperm injection and intra-uterine insemination. Other modifications include use of donor sperm where there is a male factor problem in addition, and various surgical procedures where sperm or spermatocytes are obtained from the testicles. All of these techniques are now grouped under the heading of assisted reproduction treatment and detailed description is not appropriate in a surgical operative book. Sterilisation Sterilisation as a deliberate operation is always a serious decision, and never one to be taken without considerable time for explanation, and opportunity for the patient to reflect and change her mind before embarking on the operation. Worldwide it remains a very important and frequently used method of contraception. Any surgeon who performs this operation is advised to observe precautions similar to those taken when terminating a pregnancy and similar indications frequently exist and the same principles and safeguards should be adopted. Indications for sterilisation include a patient who for personal or social reasons decides to make a permanent and irreversible decision to never subsequently conceive any child of their own.

References

• Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996; 71: 5-13.
• Merrill JP, Murray JE, Harriso- JH, et al. Successful homotra-spla-tatio- of the huma- kid-ey betwee- ide-tical twi-s. JAMA. 1956;160:277-282.
• Appenzeller O, Kornfeld M, Snyder R. Acromutilating, paralyzing neuropathy with corneal ulceration in Navajo children. Arch Neurol. 1976;33:733-738.
• Leeder S, et al. A race against time: the challenge of cardiovascular disease in developing countries. New York, 2004, Columbia University. 8.
• Gilligan TD, Seidenfeld J, Basch EM, et al. American Society of Clinical Oncology Clinical Practice Guideline on uses of serum tumor markers in adult males with germ cell tumors. J Clin Oncol 2010;28(20):3388-3404.
• Glund S, Deshmukh A, Long YC, et al. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle. Diabetes. 2007;56(6):1630-1637.
• Raggi P, Cooil B, Shaw LJ, et al. Progression of coronary calcium on serial electron beam tomographic scanning is greater in patients with future myocardial infarction. Am J Cardiol 2003;92:827.
• Liu T, Yan H, Kuismanen S, et al. The role of hPMS1 and hPMS2 in predisposing to colorectal cancer. Cancer Res 2001;61(21):7798-7802.