Figure continued on next page Subperitoneal Spread by Transvenous Spread 63 c Fig order line dapoxetine erectile dysfunction medications that cause. Hilar cholangiocarcinoma and periarterial/perineural infiltration along the replaced left hepatic artery in the gastrohepatic ligament cheap dapoxetine 60mg mastercard erectile dysfunction treatment injection therapy. A hypodense infiltration (arrow) is evident along the left hepatic artery (arrowhead) purchase dapoxetine amex impotence uk, which is replaced from the left gastric artery. This vessel runs in the gastrohepatic ligament from the lesser curvature of the stomach to the hilum of the liver. Mechanisms of Spread of Disease in the Abdomen and Pelvis ligament, mesentery, or mesocolon of the organs. The most specific signs of tumor thrombus are Tumor thrombus is commonly recognized in hepato- the presence of neoplastic vessels and enhancement cellular carcinoma, renal cell carcinoma, venous leio- of tumor thrombi in major veins that drain the myosarcoma, melanoma and pancreatic neuroendo- primary tumor. Such duce filling defects in veins adjacent to the tumor extension in other tumors is rare and may not be but without tumor vessels or enhancement of the recognized on imaging studies because they may thrombus. Carcinoma of the gastric antrum with tumor thrombus in the right gastric vein extending into the portal vein. Metastatic melanoma to the small bowel with tumor thrombus in the jejunal veins, superior mesenteric vein and portal vein. Figure continued on next page Subperitoneal Spread by Transvenous Spread 65 c Fig. Metastatic melanoma to the small bowel with tumor thrombus in the jejunal veins, superior mesenteric vein and portal vein. Large non-functioning islet cell carcinoma of the tail of pancreas with tumor thrombus in splenic and portal veins. Mechanisms of Spread of Disease in the Abdomen and Pelvis Subperitoneal Spread by Intraductal melanoma, and rare tumors such as biliary cystade- noma may grow intraductally along with obstruction Spread 19–24 of the bile duct upstream to the primary tumor. The presence of a mass in the bile duct with similar This is an uncommon mode of tumor spread from an enhancement characteristic as the primary tumor and organ with a duct or conduit draining secretion or excre- the displacement of an intraductal stent against the tion of the organ, e. When cholangiography is done either by itoneal space and can be a conduit for tumor spread. Hepatic obstruction rather than a constricting stenosis is the metastases from colorectal cancer, breast cancer, key to the diagnosis of intraductal tumor growth. Intrahepatic cholangiocarcinoma with tumor growth into the left hepatic duct and common hepatic duct in the hepatoduodenal ligament. The ana- direct bidirectional spread of disease between the tomic landmarks of vessels in the ligaments, mesen- abdomen and female pelvis via the subperitoneal tery, and mesocolon define and characterize this mode space. Takahashi T, Ishikura H, Motohara T, Okushiba of intraabdominal spread of disease. Intraperitoneal S pread of Infections andS eeded M etastases develop a mass, referred pain to the shoulder, and Intraperitoneal Infections: subcostal or flank pain. The clinical spectrum is illu- Pathways of Spread strated by this analogy: and Localization It can rapidly build up a crater of sepsis giving the patient an acute illness with a clear cut diagnosis... In the past, the most common causes from occasional rumbles, making its presence felt only by causing ill health. Today, 60–71% of such abscesses are postoperative and are Early radiologic identification and localization of particularly frequent following gastric and biliary an intraabdominal abscess are of extreme impor- 1,2 tance, since morbidity and mortality increase with tract operations and colonic surgery. Many of the cases of postoperative abscesses are secondary to ana- delay in treatment. More prompt diagnosis currently in and accurate when there is an understanding of the conditions such as peptic ulcer and appendicitis, lead- intraperitoneal routes of spread of contaminated ing to earlier surgical intervention, results in an material. The bacterial flora generally consists of multiple strains of aerobic and anaerobic organisms. The aero- Anatomic Considerations bes include particularly Escherichia coli, Streptococ- cus, Klebsiella, and Proteus; the anaerobes include The Posterior Peritoneal Attachments Bacteroides and cocci. Paralleling this epidemiologic change has been a Figure 5–1 shows the roots of the mesenteric attach- change in the clinical presentation. The fulminating ments of the intraperitoneal segments of bowel, and course described classically is no longer generally seen, Fig. The peritoneal investment of the extraperitoneal segments of the alimentary tract. The mesenteric portions of the gut have been removed, including the stomach, small bowel, transverse colon, and sigmoid colon. Underlying the visceral surface of the right lobe of the The pelvis constitutes about one-third of the volume liver, the right subhepatic space is composed of two of the peritoneal cavity and is its most dependent part compartments (Fig. The anterior subhepatic space is limited inferiorly peritoneal recesses lateral to the ascending and des- by the beginning of the transverse colon and cending colon. The right paracolic gutter is wide and mesocolon; deep and is continuous superiorly with the right sub- 2. The posterior subhepatic space lies in close rela- hepatic space and its posterosuperior extension deep tionship to the posterior parietal peritoneum overlying to the liver, which is clinically known as Morison’s the right kidney. The right subhepatic space is anatomically con- recess between the renal impression of the liver in front tinuous with the right subphrenic space around the and the upper pole of the right kidney behind. The lateral edge of the right coronary ligament of the posterosuperior extension of the right subhepatic liver. It is important to recognize that the coronary space to its margination above by the right coronary ligament actually suspends the right lobe of the liver ligament is known as either the hepatorenal fossa or 5 from the parietes posteriorly (Fig. The left paracolic gutter is spread and localization of intraperitoneal infections narrow and shallow and is interrupted from continuity since it is the lowest part of the right paravertebral groove when the body is in the supine position. Reflections of the right coronary ligament (arrows) The right subhepatic space is composed of anterior and suspending the right lobe of the liver are outlined by free posterior (Morison’s pouch) compartments and is anatomically peritoneal air in the lateral view. The nonperito- the coronary ligament mark the site of the nonperitonealized nealized bare area of the posterior surface of the right lobe lies ‘‘bare area’’ of the liver (L). Frontal view of the anatomic relationships of Morison’s pouch facing the deep visceral surface of the right lobe of the liver. Inferiorly, it is bounded by the hepatic into anterior and posterior subphrenic spaces actu- flexure of the colon and the peritoneal reflections at ally occurs, but such compartmentalization of the beginning of the transverse mesocolon and medi- abscesses frequently takes place by the formation ally by the second portion of the duodenum as it of pyogenic membranes. Laterally, it communicates deep to the liver around the margin of the right coronary ligament with the subphrenic space The Left Subphrenic Space above and the right paracolic gutter in the flank. The suspending coronary ligament of the left lobe of Although these two compartments communicate the liver, unlike the right, is attached superiorly, freely anatomically, they are frequently separated by almost in the center of the abdomen and more ante- the development of pyogenic membranes. It is quite small and usually insignificant The Right Subphrenic Space for the margination of abscess cavities. The anatomic spaces surrounding the left lobe of the liver are The right subphrenic space is a large continuous thus freely communicating. Generally, therefore, the compartment extending over the diaphragmatic whole left side should be considered as one potential surface of the right lobe of the liver to its margina- 5,7 abscess area. The mesenteric attachments of the left tion posteriorly and inferiorly by the right upper quadrant, i. A structure of particular significance in the left upper quadrant of the abdomen is the phrenicocolic 9 ligament (Figs. This is a strong falciform peritoneal fold that extends from the ana- tomic splenic flexure of the colon to the diaphragm at the level of the 11th rib. Older literature refers to it also as the ‘‘sustentaculum lienis,’’ since it is in immediate inferior relationship to and serves the purpose of sup- porting the spleen at its tip.

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Depending on the cir- depends on whether the dose or steady-state plasma cumstances cheap dapoxetine generic erectile dysfunction in teens, the dose or concentration may be plot- concentration (C ) is plotted on a linear A: or logarithmic cpss ted on a linear scale (Figure 7–2A) or a logarithmic B: scale trusted 60mg dapoxetine hard pills erectile dysfunction. Tus purchase dapoxetine 90 mg without a prescription erectile dysfunction shake recipe, the lef produce large increases in drug efect until the maxi- side of the curve is fat until the drug concentration mum efect is reached. The right side is also The curve described above represents the rela- fat, refecting the maximum physiological response tionship of drug concentration to a continuous of the body, beyond which the body simply cannot physiological response. The same relationship can respond to additional drug (with the possible excep- be used to characterize the probability of a binary tion of eating and weight). Tus, the curve is fat on (yes/no) response to a drug dose: both the lef and right sides. A sigmoidal curve is γ C required to connect the baseline to the asymptote, Probability = P0 + ( max − 0) γ γ which is why sigmoidal curves are ubiquitous when C50 + C modeling pharmacodynamics In this case, the probability (P) ranges from 0 (no The sigmoidal relationship between exposure chance) to 1 (certainty). P0 is the probability of a “yes” and response is defned by one of two interchange- response in the absence of drug. Pmax is the maximum able relationships: probability, necessarily less than or equal to 1. As γ before, C is the concentration, C50 is the concentration C Efect = E0 + Emax γ γ associated with half-maximal efect, and γ describes C50 + C the steepness of the concentration versus response relationship. Half-maximal efect is the same as 50% or probability of a response when P0 is 0 and Pmax is 1. Tis range can be mea- absence of drug, C is drug concentration, C50 is the sured either between two diferent points on the concentration associated with half-maximal efect, same concentration versus response curve, or the and γ describes the steepness of the concentration ver- distance between two distinct curves. For the frst equation, Emax such as sodium nitroprusside, a single concentra- is the maximum change from baseline. In the second tion versus response curve defnes the relationship equation, Emax is the maximum physiological mea- between concentration and decrease in blood pres- surement, not the maximum change from baseline. The therapeutic window might be the difer- Once defned in this fashion, each parameter ence in the concentration producing a desired 20% of the pharmacodynamic model speaks to the spe- decrease in blood pressure and a toxic concentration cifc concepts mentioned earlier. Highly efcacious However, for a drug such as lidocaine, the thera- drugs have a large maximum physiological efect, peutic window might be the diference between the characterized by a large Emax. For drugs that lack C50 for local anesthesia and the C50 for lidocaine- efcacy, Emax will equal E0. C50 is a measure of drug induced seizures, the latter being a separate concen- potency. Drugs lack- index is the C50 for toxicity divided by the C50 for ing potency have a high C50, indicating that a large the desired therapeutic efect. Because of the risk of amount of drug is required to achieve the drug ventilatory and cardiovascular depression (even at efect. The parameter γ indicates steepness of the concentrations only slightly greater than those pro- relationship between concentration and efect. A γ ducing anesthesia), most inhaled and intravenous value less than 1 indicates a very gradual increase hypnotics are considered to have very low therapeu- in drug efect with increasing concentration. Pharmacological antagonists reverse the efects of the agonist but do not otherwise exert an The receptors are half occupied when [D ] = k d. Competitive antagonism occurs Tus, k d is the concentration of drug associated with when the antagonist competes with the agonist for 50% receptor occupancy. Receptor occupancy is only the frst step in Noncompetitive antagonism occurs when the antag- mediating drug efect. Binding of the drug to the onist, through covalent binding or another process, receptor can trigger a myriad of subsequent steps, permanently impairs the drug’s access to the receptor. Tis the shape of the curve relating fractional receptor binding is described by the law of mass action, occupancy to drug concentration is intrinsically which states that the reaction rate is proportional to sigmoidal. However, the concentration associated the concentrations of the reactants: with 50% receptor occupancy and the concentra- tion associated with 50% of maximal drug efect kon are not necessarily the same. The rate con- by an agonist may lead to hyporeactivity (“desensi- stant kon defnes the rate of ligand binding to the tization”) and tolerance. The rate constant kof defnes the rate of enous ligand is chronically blocked, then receptors ligand unbinding from the receptor. According to may proliferate resulting in hyperreactivity and the law of mass action, the rate of receptor binding, increased sensitivity. In this equation, kd is the dissociation rate con- Keifer J, Glass P: Context-sensitive half-time and anes- stant, defned as kon/kof. Patients exposed to multiple also speed recovery: elimination of halothane anesthetics at short intervals, rebreathing, high fresh gas flows, low middle-aged obese women, and persons with anesthetic-circuit volume, low absorption a familial predisposition to halothane toxicity by the anesthetic circuit, decreased or a personal history of toxicity are considered solubility, high cerebral blood flow, and to be at increased risk. This is supported by the observation that the anesthetic potency of inhalation but is not nearly as potent a dilator as agents correlates directly with their nitroglycerin or adenosine. Anesthetic interactions at specific protein 10 The low solubility of desflurane in blood and ion channels, as well as more nonspecific body tissues causes a very rapid induction membrane effects, may combine to of and emergence from anesthesia. Nitrous oxide, chloroform, and ether were the frst make inhalation induction practical for them as universally accepted general anesthetics. Regardless of the patient’s age, anesthesia is furane and enfurane, two potent halogenated ofen maintained with inhalation agents. Emergence agents, were used for many years in North American depends primarily upon redistribution from the anesthesia practice. Up to 50% of it was metabolized by properties not shared by other anesthetic agents. En- Pharmacokinetics of furane has a nonpungent odor and is nonfammable Inhalation Anesthetics at clinical concentrations. During deep anesthesia with hypocarbia membrane proteins and ion channels, it is clear electroencephalographic changes can progress to a that producing their ultimate efect depends on spike-and-wave pattern producing tonic–clonic sei- attainment of a therapeutic tissue concentration in zures. Although with gases in the breathing circuit before being adults are usually induced with intravenous agents, inspired by the patient. The actual composition of the inspired rapidly approach the inspired gas concentration gas mixture depends mainly on the fresh gas fow (Fi). Because anesthetic agents are taken up by the rate, the volume of the breathing system, and any pulmonary circulation during induction, alveolar absorption by the machine or breathing circuit. The concentrations lag behind inspired concentrations higher the fresh gas fow rate, the smaller the breath- (F a /F i <1. The greater the uptake, the slower the ing system volume, and the lower the circuit absorp- rate of rise of the alveolar concentration and the tion, the closer the inspired gas concentration will lower the F a :F i ratio. Clinically, these Because the concentration of a gas is directly attributes translate into faster induction and recov- proportional to its partial pressure, the alveolar par- ery times. The alveolar partial pressure is important because it determines the partial pressure of anesthetic in the blood and, ultimately, in the brain. The second factor that afects uptake is alveolar Blood/ Brain/ Muscle/ Fat/ Agent Gas Blood Blood Blood blood fow, which—in the absence of pulmonary shunting—is essentially equal to cardiac output. As cardiac output increases, anesthetic uptake increases, the rise in alveolar partial pressure Isoflurane 1.

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Insight is typically poor 30mg dapoxetine for sale bisoprolol causes erectile dysfunction, and alterations in perception often reach delusional proportions dapoxetine 90 mg without prescription beta blocker causes erectile dysfunction. Most patients  Assess for potential suicide risk and refer where have ideas of reference order dapoxetine without prescription erectile dysfunction treatment singapore, thinking that others take special notice necessary or mock them for their perceived defect. In  Ask about substance abuse aesthetic surgery and laser suites the prevalence may be as high  Investigate any underlying psychiatric disease as 25–30% of patients, and so identifcation of these patients is appropriately extremely important, as they typically have a poor response to cosmetic dermatological treatments. Dissatisfaction, anger, and Depression, anxiety, anger, and somatic symptoms in even aggression toward the treating dermatologist are known. Preoccupation with the nose, ears, and pore size is Aesthet Surg 2012; 65(4): 530–2. Higher dosing The Body Dysmorphic Disorder questionnaire is an alternative regimens than those used for depression are usually required. The key elements are known as exposure, response prevention, of skin changes is important to both engage the patient and also to and cognitive restructuring. Exposure consists of having patients expose manage any skin changes appropriately. Response prevention consists of management of hair loss, or appropriate management of genuine skin helping patients avoid their repetitive behaviors. To initiate treat- and where patient’s preoccupation with skin changes seems excessive ment or referral, suggest to the patient in a gentle manner that they (see screening tools above). The Diagnostic and Statistical Manual for Mental Disor- Convey your concern regarding the amount of their time being usurped ders 5th edition. How many times a day do you usually check your skin either in a mirror or by feeling it with your fngers? How often do you feel anxious about your skin in social Pharmacologic treatment of body dysmorphic disorder: A situations? Has your skin interfered with your ability to work or study, The dysmorphic syndrome. The small sample size limits the application of this newly and erythroplasia described diagnostic tool. The prevalence of human papillomavirus genotypes in of Queyrat nonmelanoma skin cancers of nonimmunosuppressed indi- viduals identifes high-risk genital types as possible risk Thomas D. Yasuda M, Tamura A, as intraepidermal squamous cell carcinoma, the latter occurring Shimizu A, Takahashi A, Ishikawa O. The clinical appearance is that of a sharply demar- A case report highlighting the importance of early and defni- cated, erythematous plaque that is persistent and slowly enlarging. Multiple treatment options are avail- able and no one treatment is ideal for all situations. Defnitive  Cryosurgery C treatment is surgical excision if the lesion is small and well defned. Br Non-surgical options include imiquimod cream (a topical immu- J Dermatol 2000; 143: 759–66. Three lesions treated showed no recurrence at 5-year follow-  Skin biopsy up, with good cosmetic results. Cryoimmunotherapy: superfcial basal cell cancer and Topical treatment of Bowen’s disease with 5-fuorouracil. Arch Der- Only two of 26 biopsy-confrmed lesions recurred up to 10 matol 2011; 147: 1326–7. J Am Acad Dermatol apart with the methyl aminolevulinate applied for 3 hours prior 2006; 55: 901–3. Cosmetic outcomes were best after methyl Radiation therapy for Bowen’s disease of the skin. Guidelines on the use of photodynamic therapy for non- Forty-four cases of Bowen’s disease treated with radiation melanoma skin cancer: an international consensus. Interna- therapy were reviewed, demonstrating remission in 42 patients tional Society for Photodynamic Therapy in Dermatology, 2005. Scand J Urol Nephrol 2007; Three patients showed complete resolution at 4 months, 41: 507–10. A high histo- Use of the diode laser for lesions in non-glabrous skin may enhance logic recurrence rate of 3/10 was observed. Imiquimod 5% cream monotherapy for cutaneous squa- mous cell carcinoma in situ (Bowen’s disease): a random- Treatment of multiple lesions of Bowen’s disease with ized, double-blind, placebo-controlled trial. One patient was treated with oral isotretinoin 1 mg/kg daily Seventy-three percent of patients achieved clinical remission and subcutaneous interferon-α2a 3 million U three times per week with no recurrence at the 9-month follow-up. Every effort should be made to fnd the minimum dosage of systemic corticosteroids required to suppress 32 Bullous pemphigoid disease. With only a few exceptions, all elderly patients started on systemic corticosteroids should also start calcium, vitamin D, and Michelle Scott, Victoria P. All patients on systemic corticosteroids should be screened for tuberculosis and have their blood pressure and serum glucose levels followed closely. Tetracyclines combined with nicotinamide can be used for patients unable to tolerate or who have contraindications to cor- ticosteroids. Azathioprine is a second-line alternative that may be used alone or as a corticosteroid-sparing agent in more severe disease. Azathioprine has a slow onset of action and should be started in conjunction with corticosteroids during Courtesy of Katherine Evans the acute stage. It is generally well tering disease that mainly affects elderly patients, although child- tolerated and does not carry the risk of liver toxicity seen with hood cases do occur. Dapsone is particularly useful when histologic activation of complement and release of tissue-destructive pro- examination reveals a predominance of neutrophils. The clinical hallmarks of the eruption are tense and immunomodulatory therapies have demonstrated effcacy, bullae with either generalized or localized distribution; however, including intravenous immunoglobulin, chlorambucil, pulsed intrave- variants, including urticarial, vesicular, vegetative, erythrodermic, nous corticosteroids, cyclophosphamide, cyclosporine, etanercept, ritux- and nodularis, have been described. Mortality can be high in patients pemphigoid: Recommendations by an international panel of with poor overall health and advanced age. The review focused on evidence from 10 randomized controlled trials to help guide physicians with treatment. While  Evaluation of medications to rule out drug-induced the quality of evidence from the majority of the trials was limited cases by small sample size and lack of blinding, two of the 10 studies  Consider patient age and overall medical condition were large and included more than half of the participants in the for therapeutic decision making review (Joly 2002, Joly 2009). These are the only  Consider fasting glucose screening recommendations with strong evidentiary support. Arch Dermatol 2005; 141: Treatment of bullous pemphigoid with prednisolone only: 691–8. A multicenter ran- The only prospective trial evaluating factors that infuence sur- domized study. They showed A randomized, prospective study of 50 patients found no that disease activity had no correlation with mortality. Echigo T, Hasegawa M, Inaoki M, Minocycline as a therapeutic option in bullous pemphi- Yamazaki M, Sato S, Takehara K. A higher prevalence of antiphospholipid antibodies was A retrospective analysis of 22 patients treated with adjuvant detected in patients with autoimmune blistering diseases (pem- minocycline (50–100 mg daily) showed a major response in six phigus vulgaris, pemphigus foliaceous, bullous pemphigoid, cica- patients, a minor response in 11, and no response in fve. Of the 10 patients with an autoimmune blistering Generalized bullous pemphigoid controlled by tetracy- disease and positive antiphospholipid antibodies, seven were cline therapy alone. A total of 341 patients were enrolled in a non-blinded, ran- Of 11 patients on long-term maintenance therapy with systemic domized, multicenter trial and were stratifed by disease severity corticosteroids, nine remained symptom free on azathioprine (moderate or extensive).

By L. Rasul. DePauw University.