Marie Adorno, APRNC, MN

• Associate Professor of Nursing
• Our Lady of Holy Cross College
• New Orleans, Louisiana

Complications due to postoperative radiotherapy on primary nasal reconstructions most commonly occur to the structural components reconstructing the nasal bones and overlying skin erectile dysfunction treatment massachusetts purchase extra super levitra 100 mg free shipping, as well as alar retraction and general thinning of the soft tissue envelope [5] erectile dysfunction at age 50 purchase cheap extra super levitra on line. Primary or secondary implant insertion should also be considered for ear prosthesis erectile dysfunction doctors northern virginia generic 100mg extra super levitra with mastercard. Magnets or a bar can be secured onto the implants so that a prosthetic ear may be attached erectile dysfunction drugs staxyn buy extra super levitra 100 mg free shipping. Oropharynx the use of transoral techniques for oropharyngeal resections erectile dysfunction doctor vancouver generic extra super levitra 100 mg with mastercard, the defects from which are generally not reconstructed erectile dysfunction doctors in south jersey discount extra super levitra 100mg without a prescription, result in better functional outcomes than when the oropharynx is reconstructed with a denervated non-sensate soft tissue flap. In most circumstances where the oropharynx needs reconstruction a mandibulotomy is required. Tongue base reconstruction Function of the tongue base can generally only be preserved if less that half the tongue base has been resected. When reconstruction is required, pedicled regional options include the pectoralis major, buccinator, submental island and supraclavicular flaps. Lateral pharyngeal wall reconstruction Transoral resection without reconstruction might not always be appropriate for tumours of the lateral pharyngeal wall. This can occur when tumours are too large for transoral surgery, involve (or expose the mandible and during salvage surgery. Pedicled flaps such as the pectoralis major and submental island flaps are good locoregional reconstructive options. The functional implications of total soft palate resection are significant and the patient should be counselled about the Temporal bone the aims of reconstruction should address the following issues: Protection for the brain where the dura has been breached the skin defect the auricular defect the tissue volume deficit Any mandibular defect Facial nerve dysfunction Cerebral protection is of paramount importance and dural defects can be repaired with non-vascularised tissue, such as autologous fascia lata grafts, xenografts or synthetic materials [6]. Smaller skin defects with smaller volume loss can be reconstructed with local pedicled flaps. It provides a large quantity of skin, has minimal donor site morbidity, can be harvested with a vascularised nerve graft, and allows for harvest of fascia lata or the lateral cutaneous nerve of the thigh. Where mandibular reconstruction is also required, a chimeric flap, such as a scapular osteomyocutaneous flap, can be employed instead. Jejunal free flap Gastro-omental free flap Hypopharynx Reconstruction of partial and circumferential hypopharyngeal defects present major challenges. Modern chemoradiotherapy protocols, medical co-morbidity and poor nutritional status increase surgical morbidity. The aims of hypopharyngeal reconstruction are to: Restore swallowing Allow speech rehabilitation Limit morbidity and mortality Partial hypopharyngeal defects with more than 3. The most widely used pedicled options are the pectoralis major and supraclavicular flaps. Any longitudinal strip of native pharyngeal mucosa that can be preserved is extremely useful, as it tends to reduce the stricture rate and improves functional outcomes of the neopharynx. Debate exists when less than 1 cm width of native pharyngeal mucosa remains, with some believing it better to excise this, thereby creating a circumferential defect allowing for easier flap inset. There are concerns about the viability of narrow strips of mucosa, particularly in the irradiated patient. Others believe that preserving even this small amount of mucosa may reduce stricture rates. Limited case series suggest speech and swallow outcomes may be improved with free compared to pedicled flaps but these are highly flawed and far from definitive. The pectoralis major can be harvested as a myocutaneous flap for this purpose or a muscle-only flap can be covered by a split-thickness skin graft. The jejunal and gastroomental free flaps do have the advantage of containing omentum, which can be used to provide vascularised tissue coverage over the anastomosis in much the same way a pectoralis major pedicled flap would. An alternative to a tubed flap reconstruction is a U-shaped one, with the ends sutured directly onto the prevertebral fascia. The advantage of this is that pedicled flaps can be used, generally a pectoralis major, which then do not require the extreme width necessary for tubing. Of course this can only be an option so long as the prevertebral fascia has not been resected as a margin. All reconstructive options carry with them the risk of anastomotic leak, flap failure and donor site morbidity. Anastomotic stricture is a potential complication resulting in dysphagia and, with the tubed flaps, this generally occurs at the inferior anastomosis, whilst the superior anastomosis is more prone to leak. Reconstruction in head and neck surgical oncology 231 Total circumferential hypopharyngeal/ oesophageal defects inferior to the clavicles After circumferential resection of the distal hypopharynx/proximal oesophagus, including a 3 cm margin, the lower anastomosis for any tubed flap would be inferior to the clavicles. This procedure carries significant morbidity due to the need to enter three visceral cavities (neck, thorax and abdomen). Intraoperatively, the patient also experiences cardiac arrhythmia as the surgeon manually frees the oesophagus from the posterior surface of the heart. Colonic transposition is a far less widely used alternative, which carries all the same complications as gastric pull up, but has a greater proximal reach, being able to reconstruct pharyngeal defects which extend as far as the oropharynx. Salvage surgery Surgery in general and especially reconstructive surgery in the post-(chemo)radiotherapy era carries a higher complication rate due to scarred fibrotic tissue, reduced tissue vascularity and poor wound healing in the irradiated field [12]. Up to 50% of patients undergoing salvage total laryngectomy after chemoradiation will suffer from postoperative pharyngocutaneous fistulae. Introducing vascularised tissue from outside the radiation field as overlay to any pharyngeal repair or reconstruction can significantly reduce fistula rates [13]. The gold standard for this is a pectoralis major pedicled flap overlaid on the pharyngeal repair in these previously irradiated cases. Pedicle ligation When ligating the vascular pedicle of a free flap immediately to transfer, Ligaclips should not be applied to the flap side. The flap can then be allowed to drain of blood prior to being moved to the site of the defect. This removes the need to adapt a reconstruction plate intraoperatively when no pre-bent plate is available, but probably reduces the overall stability of the initial reconstruction. Microvascular anastamosis Microvascular anastomoses can be undertaken either using at least 4. The microscope provides superior magnification and illumination, and affords both the surgeon and assistant similar views. The venous coupler is an adjunct that does speed up the time taken for end-to-end venous anastomosis and is relatively simple to use, but it cannot be used for true end-to-side anastomosis. Skin grafting for donor site When a split-skin graft is harvested for donor site coverage, this should be harvested using the air-powered dermatome at a thickness of between 0. Pressure must be applied and maintained to the grafted area to prevent haematoma and shearing. This can be achieved by the use of sterile sponge secured with either staples or suture bolsters or by using fluffed gauze with overlying suture bolsters. If they enter high, for instance through the skin overlying level 5b, they can be passed posterior to the accessory nerve and cervical plexus branches, thereby preventing the drain from migrating anteriorly and sucking on the flap pedicle, or worse, a microvascular anastomosis, which tend to lay lower in the neck. Immediate postoperative care should include the following [15]: Continued sedation and ventilation as per the Avoidance of circumferential neck ties securing Avoid inotropes/vasopressors. Postoperative care the first 48 hours after free flap surgery are the most crucial. Flap checks should be every 15 minutes for the first hour, every 30 minutes for the following 2 hours and then houtrly for the next 24 hours. If vasopressor use is unavoidable in order to keep the systolic blood pressure above 100 mmHg, the judicious use of metaraminol is best tolerated in head and neck free flap patients [16]. Ideally haemoglobin should be maintained above 80 g in order to ensure good perfusion of the flap. However, concern has been raised over transfusion increasing risk of haematogenous metastasis and recurrence, as well as increasing risk of thrombosis and flap failure [17]. This consists of a silastic sleeve with an attached electronic flow sensor which is wrapped around the vascular pedicle. Use of the implantable Doppler has revolutionised the postoperative monitoring of free flaps. Whilst the implantable Doppler is not a replacement for good regular clinical examination postoperative free flaps, it is an extremely useful adjunct, especially for those not very familiar with the aftercare of free flaps and for flaps without a visible skin paddle. Should the Doppler signal be lost, the surgical team must be immediately informed and, after careful corroborating clinical evaluation of both the patient and flap, an emergency return to theatre for flap salvage planned. Pedicled flap postoperative care the postoperative care of pedicled flaps in contrast to free flaps is far less onerous. Where a skin paddle or flap muscle is visible, flap health can be assessed by warmth, turgor and skin capillary refill. Should the patient develop a significant neck haematoma, this must be drained early to prevent risk to the vascular pedicle. The neck should be observed and palpated to ensure that it is soft with no sign of haematoma or fistula. Where possible, the flap skin paddle should be observed for colour, bearing in mind what it looked like immediately postoperatively. The flap should be palpated for warmth, turgor and capillary refill (press for 5 seconds, refill <2 seconds). The wound edges between the inset of the skin paddle and native tissue should be inspected for dehiscence, predisposing to fistula. Observe whether the patient is being ventilated or breathing spontaneously, and check the ventilator settings. Distal donor limbs should be examined for warmth, capillary refill (<2 seconds), and movement where appropriate. Flap salvage the standard quoted flap failure rate in the literature is up to 5% [16,18]. Although problems with the venous anastomosis are more common than those of the arterial anastomosis, patient factors also play a key role, such as hypotension, anaemia and the effect of pre-existing co-morbidities including intraoperative events that have occurred as a result of these. Should the Doppler signal be lost, especially within the first 48 hours following surgery, and this corroborated by the clinical examination, an emergency return to theatre should be organised including perioperative work-up including group and save. Intraoperatively, any neck haematoma must be removed, and the arterial and venous anastomoses scrutinised. Problems with the arterial inflow or venous outflow from the flap must be identified and addressed. This can involve taking down the existing microvascular anastomoses and revising them. Oncologic safety of the submental flap for reconstruction in oral cavity malignancies. Buccinator myomucosal flap: Clinical results and review of anatomy, surgical technique and applications. Reconstruction of the hypopharynx after surgical treatment of squamous cell carcinoma. Circumferential pharyngeal reconstruction: History, critical analysis of techniques, and current therapeutic recommendations. Mortality and morbidity of primary pharyngogastric anastomosis following circumferential excision for hypopharyngeal malignancies. The current role of salvage surgery in recurrent head and neck squamous cell carcinoma. Preventing pharyngocutaneous fistula in total laryngectomy: A systematic review and meta-analysis. Intensive care unit versus non-intensive care unit postoperative management of head and neck free flaps: Comparative effectiveness and cost comparisons. Intraoperative use of vasopressors does not increase the risk of free flap compromise and failure in cancer patients. Reconstruction in head and neck surgical oncology 235 a predictor of recurrence and survival in head and neck cancer surgery patients. Physicians must learn how to choose the correct drug dosage for different conditions to ensure effective and safe therapy. This article reviews the basic concepts of pharmacokinetics and pharmacodynamics, followed by guidelines on how to use this information to optimize therapeutic applications. Drug interactions and adverse drug responses are briefly discussed, with advice on how both can be recognized and minimized in clinical practice. Lastly, the increasing role of pharmacogenomics in individualizing therapy beyond preventing or predicting adverse drug responses is discussed. This variability has become a concern with the increasing use of generic preparations. After delivery of a drug into the systemic circulation either directly by intravenous injection or after absorption, the drug is transported throughout the body, initially to the well-perfused tissues and later to areas that are less perfused. For an intravenously administered drug, when absorption is not a factor, the initial phase-from immediately after administration through the rapid fall in concentration-represents the distribution phase, during which a drug rapidly disappears from the circulation and enters the tissues. This is followed by the elimination phase (see later), when drug in the plasma equilibrates with drug in the tissues. Drugs are removed from the body by two major mechanisms: hepatic elimination, in which drugs are metabolized in the liver and excreted through the biliary tract; and renal elimination, in which drugs are removed from the circulation by either glomerular filtration or tubular secretion. For most drugs, the rates of hepatic and renal elimination are proportional to the plasma concentration of the drug. The efficiency of elimination can be assessed by quantifying how fast the drug is cleared from the circulation. Drug clearance is a measure of the volume of plasma cleared of drug per unit of time. It is similar to the clinical measurement used to assess renal function-creatinine clearance, which is the volume of plasma from which creatinine is removed per minute. Total drug clearance (Cltot) is the rate of elimination by all processes (Eltot) divided by the plasma concentration of the drug (Cp): Cl tot = El tot C p (2) Drugs may be cleared by several organs, but as noted earlier, renal clearance and hepatic clearance are the two major mechanisms. Total drug clearance (Cltot) can best be described as the sum of clearances by each organ.

Etiology and Pathophysiology Acute kidney injury is a clinical diagnosis and not a structural one best erectile dysfunction doctors nyc buy extra super levitra canada. It is not a single disease but a heterogeneous group of conditions that share common diagnostic features namely an increase in serum creatinine often associated with a reduction in urine volume impotence vs infertile order generic extra super levitra. Prerenal azotemia ["azo erectile dysfunction treatment manila discount 100 mg extra super levitra fast delivery," meaning nitrogen erectile dysfunction cpt code cheap extra super levitra american express, and "-emia erectile dysfunction treatment options uk best order extra super levitra," meaning in the blood (refer Table 20 erectile dysfunction drug stores purchase 100mg extra super levitra. Prerenal azotemia does not produce damage to renal parenchymal and is rapidly reversible once parenchymal blood flow and intraglomerular hemodynamics are restored. Obstruction to urinary flow may be caused by derangements anywhere from the renal pelvis to the tip of the urethra. This leads to increased retrograde hydrostatic pressure and interferes with glomerular filtration. Urinary findings in different types of acute kidney injury is presented in Table 20. It is usually associated with shedding of granular casts and tubular cells into the urine. Frank necrosis is rarely observed in a kidney biopsy in patient with acute tubular injury/necrosis. This can develop due to various conditions such as severe trauma, blood loss, acute pancreatitis and septicemia. Vascular causes: Ischemia to tubules may also occur due to vascular causes that lead to reduced intrarenal blood flow, as in microscopic polyangiitis, malignant hypertension, and thrombotic microangiopathies. It may also be produced by endogenous toxins such as mismatched blood transfusions and other hemolytic crises, as well as myoglobinuria. Injury to the Tubular Epithelial Cells Proximal tubular epithelial cells are sensitive to hypoxemia and vulnerable to nephrotoxins. Factors that predispose tubular epithelial cells to toxic and ischemic injury are: Elevated intracellular concentrations of various molecules that are resorbed or secreted across the proximal tubule. These are concentrated because of the resorption of water from the glomerular filtrate. Structural alterations in epithelial cells due to ischemia are presented in Flowchart 20. Consequences of Tubular Injury Luminal obstruction by casts: Injury to the tubular epithelial cells causes detachment of the damaged cells from the basement membranes. When there is sufficient build-up of tubular debris, it can block the outflow of urine (obstruction by forming casts) in the tubules. Back-leakage of fluid from lumen into the interstitium: It occurs in the damaged tubules results in decreased urine output, interstitial edema (due to back leak into the interstitium) causes increased interstitial pressure, and further damage and collapse of the tubule. Interstitial inflammation: Ischemic tubular cells also produce chemokines, cytokines, and adhesion molecules. Disturbances in Blood Flow Ischemia also causes vasoconstriction (intrarenal) and reduces both glomerular blood flow and oxygen supply to tubules. Recovery: the tubular necrosis is patchy and there is maintenance of the integrity of the basement membrane along many segments. This allows repair of the injured foci of tubular epithelial cells and recovery of function if the precipitating cause is removed. The lesions are most marked in the proximal tubules and the ascending thick limbs of the loop of Henle in the outer medulla. Sloughing of the apical cytoplasm of non-necrotic tubular cells into the lumen of the tubules. Formation of casts: Sloughed apical cytoplasm, non-necrotic and necrotic cells form hyaline casts and brown pigmented granular cast. Occlusion of tubular lumens: the casts occlude the lumen and result in dilation of the lumen. Urinary casts in urine sediment provide important clues for differentiating renal diseases. Recovery Phase During this phase, there is a steady increase in urine volume, which may reach up to 3 L/day. There is loss of large amounts of water, sodium and potassium (leading to hypokalemia) in the urine. Consequences: Unrelieved obstruction almost always leads to: n Renal dysfunction (obstructive nephropathy) and permanent renal atrophy. Definition: Hydronephrosis is defined as an aseptic dilation of the renal pelvis and calyces due to obstruction of urinary outflow, associated with progressive atrophy of the kidney. Functional disorders: Neurogenic bladder (spinal cord damage or diabetic nephropathy). Obstruction in the urinary tract leads to accumulation of urine proximal to the obstruction. Dilatation: Even with complete obstruction, glomerular filtration does not stop but continues for some time and leads to accumulation of urine causes dilatation of affected calyces and pelvis due to back pressure. Raised pressure in the renal pelvis transmitted back through the collecting ducts into the renal parenchyma and its consequences are: n Renal atrophy n Compresses the renal vasculature of the medulla reduces the blood flow to the medulla with diminished tubular function. Interstitial inflammation: Obstruction also initiates an interstitial inflammatory reaction and interstitial fibrosis. Write short answer on morphology (gross and microscopy) of kidney in hydronephrosis. Level of Obstruction Depending on the level of urinary obstruction, the dilation may first affect the bladder, or ureter and then the kidney. Renal parenchyma shows destruction due to severe pressure atrophy and thinning of the cortex. For example, calculi in the ureters may present with renal colic, and prostatic enlargements may present with bladder symptoms. Unilateral complete or partial hydronephrosis may be silent due to maintenance of adequate renal function by the unaffected kidney. Bilateral partial obstruction may manifest as polyuria and nocturia due to inability to concentrate the urine (tubular dysfunction). Hydronephrosis: Dilation of the renal pelvis and calyces due to obstruction of urinary outflow. Stones may be formed anywhere in the urinary tract, but most are found in the renal pelvis and calyces of kidney. Terminology Nephrolithiasis (renal stones)-stones within the collecting system of the kidney. Urolithiasis (urinary calculi/stones)-stones anywhere in the collecting system of the urinary tract. A primary bladder stone is one that develops in sterile urine; it often originates in the kidney. A secondary stone occurs in the presence of infection, outflow obstruction, impaired bladder emptying or a foreign body. Many inborn errors of metabolism (like gout, cystinuria, and primary hyperoxaluria) are characterized by excessive production and excretion of stone-forming substances. Other factors: n Individual factors n Geography n Diet: Deficiency of vitamin A causes desquamation of epithelium and these cells may form a nidus on which a stone can be deposited. Stone formation are common when urine is infected with urea-splitting streptococci, staphylococci and, especially Proteus. Decreased urinary citrate: Citrate in urine present as citric acid and is under hormonal control. It tends to keep otherwise relatively insoluble calcium phosphate and citrate in solution. There are two main steps involved in stone formation: Initiation and propagation of stones. Increased urinary concentration of stone constituents: It is the most important factor in stone formation exceeds their solubility (supersaturation). Precipitation of Crystals Deficiency in inhibitors of crystal formation in urine enhances precipitation of crystals. These inhibitors include: pyrophosphates, citrates, glycosaminoglycans, osteopontin, and a glycoprotein called nephrocalcin. The mucoproteins in the urine provide the organic nidus on which the crystals form. Shape: Stones may have smooth contours or may be irregular, jagged mass of spicules. Calcium Stones (Oxalate Calculus/Calcium Oxalate) Most (80%) renal stones are composed of calcium complexed with oxalate (calcium oxalate) or phosphate (calcium phosphate) or a mixture of these (calcium oxalate + calcium phosphate). Causes include: Hyperabsorption of calcium from the intestine (absorptive hypercalciuria), an intrinsic impairment in renal tubular reabsorption of calcium (renal hypercalciuria) or idiopathic. Hypercalcemia and hypercalciuria: It is found in about 10% of patients and may be due to hyperparathyroidism, diffuse bone disease, or sarcoidosis. Hyperuricosuria: It causes "nucleation" of calcium oxalate in the collecting ducts. Hemorrhage from the mucosa of the renal pelvis may be produced by its sharp edges and blood may cover the stone making it to appear black. They are composed of calcium phosphate often with magnesium and ammonium phosphate, and are known as struvite stones or triple phosphate stones. Etiology They develop after infections of the urinary tract by urea-splitting bacteria. Complications: Intractable urinary tract infection, pain, bleeding, and perinephric abscess. Uric Acid and Urate Stones Etiology Commonly found in patients with hyperuricemia. However, more than 50% of patients have neither hyperuricemia nor increased urinary excretion of uric acid. Cystine Stones Etiology Cystine stones are uncommon and associated with cystinuria, which is due to genetic defects in the renal reabsorption of cystine or other amino acids. Clinical Features of Renal Stones Stones may be asymptomatic or may obstruct urinary flow or produce ulceration and bleeding. Larger stones cannot enter the ureters and are likely to remain silent within the renal pelvis. Stones also predispose to superimposed infection and may also cause significant renal damage. Complications of Renal Stones Hematuria Hydronephrosis due to obstruction Pyelonephritis and pyonephrosis Carcinoma: Stones can cause squamous metaplasia and later squamous cell carcinoma. Calcium stones (~80%): Composed of calcium oxalate or calcium phosphate or mixture of both. Triple stones or struvite stones (~10%): Composed of magnesium, ammonium and phosphate. Renal Cell Carcinoma (Adenocarcinoma of the Kidney, Hypernephroma, Grawitz Tumor) Q. Because of their gross yellow color and the microscopic resemblance of the tumor cells to clear cells of the adrenal cortex; these tumors were originally thought to arise from embryonic adrenal rests and were called hypernephroma. Etiology Risk Factors Tobacco: Cigarette and pipe smoking Obesity (mainly in women) Hypertension Unopposed estrogen therapy Exposure to asbestos, petroleum products, and heavy metals Chronic renal failure and acquired polycystic disease Tuberous sclerosis. It is characterized by leiomyomata (cutaneous and uterine) and an aggressive type of papillary carcinoma with increased tendency for metastatic spread. Hereditary papillary carcinoma: It is autosomal dominant form with multiple bilateral tumors showing papillary growth pattern. It is characterized by lesions of skin (fibrofolliculomas, trichodiscomas, and acrochordons), lung (cysts or blebs), and renal tumors of various histological subtypes. Both sporadic and familial forms of renal cell carcinoma can be classified depending on the cytogenetics, genetics, and microscopic features into five major types. Cytogenetic abnormalities: n Sporadic form: (1) trisomies 7, 16, and 17, and (2) loss of Y in male patients n Familial/hereditary form: Trisomy 7. Chromophobe Renal Carcinoma ~5% of renal cell carcinomas Cytogenetic abnormalities: Multiple chromosome losses and extreme hypodiploidy Cell of origin: Arise from intercalated cells of renal collecting ducts Excellent prognosis compared to clear cell and papillary cancers. Collecting Duct (Bellini Duct) Carcinoma ~ 1% or less of renal carcinoma Cell of origin: Arise from the medullary collecting duct and occur in the medullary region. Medullary carcinoma is a morphologically similar tumor developing in patients of sickle cell trait. Cytogenetic abnormalities: No distinct pattern but several chromosomal losses and deletions have been described.

Clinical Features It usually manifests with polyuria and polydipsia due to reduced tubular function erectile dysfunction diagnosis treatment buy extra super levitra 100 mg online. The deterioration in renal function is sufficiently severe to result in retention of nitrogenous wastes in the body (uremia) and other waste products normally cleared by the kidneys (elevation of serum creatinine) erectile dysfunction losartan buy extra super levitra on line amex. Xp11 Translocation Carcinoma It is a genetically distinct subtype of renal cell carcinoma that develops in young individuals erectile dysfunction doctor mumbai purchase extra super levitra 100 mg online. But may show some breach in the renal capsule and invasion into the perinephric fat diabetes and erectile dysfunction health purchase cheapest extra super levitra and extra super levitra. The clear cytoplasm is due to glycogen and lipids; which are removed by the water and solvents (xylene) used during processing of tissue for histopathological examination erectile dysfunction new treatments cheap extra super levitra 100mg with amex. Interstitial foam cells are common in the fibrovascular stalks/cores of papillary projections erectile dysfunction doctors rochester ny buy genuine extra super levitra online. The tumor cells have prominent cell membranes, pale eosinophilic cytoplasma and a halo around the nucleus (perinuclear halo). Collecting Duct Carcinoma It consists of nests of malignant cells separated by prominent fibrotic stroma. It shows irregular channels lined by highly atypical epithelium with a hobnail pattern. Clinical Features Classical diagnostic triad (seen in only 10% of cases) of renal cell carcinoma are: Costovertebral or flank pain Palpable abdominal mass Hematuria (most reliable). Renal cell carcinoma can produce ectopic hormones and paraneoplastic syndromes (Table 20. Spread Patients may develop wide metastasis before giving rise to any local symptoms or signs. Lymphatic spread: It spreads to regional lymph nodes and occurs when tumor extends beyond renal capsule. Most common sites are lungs (cannon ball deposits and pulsating secondaries) bones liver adrenal brain. A 55-year-old man presents to urology department with complaints of feeling of fullness and pain in right flank of his abdomen, and gross painless hematuria. On physical examination, a right-sided flank mass was palpable on bimanual examination. Papillary carcinoma of kidney: Most common cytogenetic abnormalities are trisomies 7,16, and 17. Erythropoietin: Major source is interstitial cells in peritubular capillaries and tubular epithelial cells. Pathogenesis and Genetics In most (90%) cases, the Wilms tumor is sporadic and unilateral. In about 5% of cases, Wilms tumor arises in three congenital syndromes at an early age and often bilaterally. Nephrogenic rests (small foci of persistent primitive blastemal cells, which are precursor lesions of Wilms tumors) are seen in the renal parenchyma adjacent to bilateral Wilms tumors. Blastemal component: It consists of small, round to oval blue cells with scanty cytoplasm. Immature stromal (mesenchymal) component: It consists of undifferentiated fibroblast-like spindle cells or myxoid tissue. Immature epithelial component: Epithelial cells show differentiation in the form of small abortive (embryonic) tubules or immature glomeruli. Classically, the tumor shows triphasic (all three cell types) combination, although the percentage of each component varies. Occasionally, they contain only two elements (biphasic) or even only one (monophasic). Clinical Features Most children present with an abdominal mass, when large it may extend across the midline and down into the pelvis. Others: Hematuria, pain in the abdomen, intestinal obstruction, and pulmonary metastases are other patterns of presentation. Prognosis Clinical parameter: Children younger than 2 years of age have a better prognosis. Histological parameter: n Invasion of the renal capsule is associated with poor prognosis. Most of the epithelial tumors of the bladder are composed of urothelial (transitional) cell type and are known as urothelial (transitional) tumors. Many of urothelial tumors are multifocal and are most commonly seen in the bladder. But they may develop at any site where there is urothelium, from the renal pelvis to the distal urethra. Noninvasive papillary tumors: They show a range of atypical changes in the urothelial cells, and are graded according to their biological behavior. Epidemiology More common in developed than in developing countries, and in urban than in rural dwellers. Risk Factors of Urothelial Carcinoma Cigarette smoking: It is the most important risk factor and risk depends on the amount of smoking and smoking habits. Industrial exposure to arylamines: the aromatic amines (naphthylamine) and azo dyes that were widely used in the past in the aniline dye and rubber industries are associated with bladder carcinoma. More than three-fourth of the cancers are squamous cell type, and remaining urothelial type. Cyclophosphamide: It produces hemorrhagic cystitis, and increases the risk of carcinoma of the bladder. Radiation: Previous exposure of the bladder to irradiation (for other pelvic malignancies). Genetic Alterations in Urothelial Carcinoma Chromosome 9 monosomy or deletions: It frequently occurs in superficial papillary tumors and rarely in noninvasive flat tumors. General morphological features of urothelial tumors are: Site: Most urothelial tumors arise from the lateral or posterior walls at the bladder base. Size varies from small (less than 1 cm in diameter) to large masses (up to 5 cm in diameter). Microscopy Noninvasive Urothelial Lesions Urothelial papilloma It is uncommon (<4% of noninvasive bladder neoplasms) and consists of two histological forms: Classical exophytic papilloma and inverted papilloma. They have a central core of loose fibrovascular tissue covered by urothelium that is microscopically have normal appearance and thickness. Inverted papillomas these are rare and appear as nodular lesion in the mucosa of the urinary bladder, usually in the trigone area. They consists of invagination of inter-anastomosing cords of normal transitional epithelium, down into the lamina propria. The lining urothelium is thicker and/or more cellular than seen in normal urothelium and in papilloma. The nuclei may be slightly enlarged and more crowded relative to normal urothelial nuclei. The chromatin is uniformly even, without the scattered hyperchromatic nuclei seen in low-grade papillary carcinoma. Noninvasive Papillary Urothelial Carcinoma Definition: Papillary urothelial carcinoma is a papillary urothelial neoplasm with some cytological and architectural disorder seen at low to intermediate magnification. The lining urothelium consists of cytologically malignant cells is of variable thickness. Gross: On cystoscopy, it appears as areas of erythema (may be focal, multifocal, or diffuse) and may be difficult to identify. Cytological features Cells: Appearance of individual tumour cells may be quite variable. Nuclei: Large pleomorphic and hyperchromatic nuclei with one or more irregular nucleoli. Infiltrating Urothelial Carcinoma It is common malignant neoplasm of the urinary bladder. Definition: Infiltrating urothelial carcinoma is characterized by divergent differentiation of lining urothelial cells and invasion beyond the basement membrane. Microscopy: Remarkable for its diversity of morphological manifestations and can present with a wide range of architectural patterns. In larger nests, the tumour cells may show stratified architecture, with the nuclei lined up perpendicular to the basement membrane and with some maturation towards the centre recapitulating the structure of urothelium. This can produce a squamoid appearance, which should be distinguished from true squamous differentiation. Since significant outcome differences have been found between low- and high-grade invasive tumors, it is necessary to identify the grade of tumor. Tumors with the more infiltrative cords and single cell patterns have worse prognosis. Clinical Course of Bladder Cancer Painless hematuria: Sometimes, it may be the only clinical feature. Complications: When the tumor obstructs the ureteral orifice, it may lead to pyelonephritis or hydronephrosis. Recurrences: Urothelial tumors, irrespective of their grade may recur, usually at different sites than the original tumor. Prognosis: It depends on the histologic grade and the stage at the time of diagnosis. Laboratory diagnosis: Cytologic examinations of urine for malignant cells and biopsy of the tumor. Various components of normal urine with their reference value is presented in Table 20. Mother also complained that he passes dark brown (red or cola) colored (smoky) urine and the urine output was reduced (oliguria). On enquiry, mother informed that about 2 weeks back the child had upper respiratory tract infection. Describe the light microscopy, immunofluorescence and electron microscopic findings. Two weeks back the child had upper respiratory tract infection, favors poststreptococcal disease. Describe the light microscopy, immunofluorescence and electron microscopic findings (refer page 665). Case 2 History: A 6-year-old child was brought to the hospital for the complaint of increased puffiness around his eyes and he has become less active over the past 10 days. Examination: On physical examination, the boy had facial puffiness which is more prominent around his eyes and also had swelling of both ankles. Describe the light microscopic, electron immunofluorescence findings in this condition. Steroid-responsive proteinuria in a child is feature nephrotic syndrome due to minimal change disease and is the most common cause for nephrotic syndrome in children. The subsequent fall in plasma oncotic pressure leads to redistribution of extracellular fluid to the interstitial compartment, producing edema. Nephrotic syndrome should be distinguished from nephritic syndrome (characterized by hematuria, uraemia and a degree of renal failure). However, on electron microscopy, shows effacement of podocyte foot processes (fusion of podocyte foot processes) in the glomerulus and is the only pathologic finding found on electron microscopy. Case 3 History: A 57-year-old female admitted to the hospital with a history of increasing back pain and fevers for the last 3 days. There is no history of burning micturition or colicky abdominal pain or chronic ingestion of analgesics. On palpation, there is tenderness over the left loin without any tenderness on anterior abdomen. Diabetic and immunocompromised patients are predisposed to urinary tract infection. The symptoms of increasing back pain and fevers without burning micturition suggests an upper tract rather than lower urinary tract infection. Urine for culture and sensitivity will help in identify the causative organism and sensitivity of the organism to the antibiotics. Case 4 History: A 29-year-old female complains of fever and burning sensation when passing urine for the last 3 days. She also complains that she voids urine more often than usual without any sense of urgency and suffering from severe lower back pain that started 1 day back. She has never had this problem in the past and she is not taking any regular medications. There is no history of vaginal discharge or urinary incontinence except an episode of cystitis 3 months ago. Abdominal examination shows suprapubic tenderness and marked tenderness in both loins. Acute pyelonephritis is much more common in females than males and occurs due to ascending bacterial infection from lower to upper urinary tract. For other causative organisms include other enteric gram-negative bacteria such as Proteus, Klebsiella, Enterobacter and Pseudomonas species. Case 5 History: A 65-year-old male complaints of vague history of generalized weakness anorexia, bony pains and impotence for the past few months.

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