Postprostatectomy incontinence

Postprostatectomy incontinence is a bothersome complication of radical prostatectomy. Although most men recover from initial postprostatectomy incontinence, some do not. It is important to understand the natural history of postprostatectomy incontinence as well as conservative measures to hasten continence. This article reviews our current understanding of postprostatectomy incontinence with an emphasis on diagnosis and management.     

Eosinophilic esophagitis: Pathophysiology and optimal management

Eosinophilic esophagitis (EoE) is an increasingly recognized disease characterized by esophageal symptoms accompanied by increased esophageal mucosal eosinophilia. The reasons for the increasing prevalence and understanding of the pathogenesis of EoE are areas of active investigation. Food and environmental allergy, host immunologic predisposition, and interactions with gastroesophageal reflux disease have emerged as important aspects of the disease. The optimal management of EoE is controversial and evolving. Therapeutic options include medical therapy with acid suppression, corticosteroids, and biologic agents. Elimination diets and endoscopic esophageal dilation have shown effectiveness. Management strategies for individual patients range from clinical observation to multimodal therapy, depending on the clinical presentation.     

Hyponatremia in cirrhosis:Pathophysiology and management

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension.The development of ascites in patients with cirrhosis is multi-factorial.Portal hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system,sympathetic nervous system and antidiuretic hormone(ADH).The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of ascites.Although not apparent in the early stages of cirrhosis,the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solutefree water.This leads to additional compensatory mechanisms including non-osmotic secretion of ADH,also known as arginine vasopressin,further worsening excess water retention and thereby hyponatremia.Hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis,and is an important prognostic marker both before and after liver transplant.The management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious.In this review,we discuss the pathophysiology and various treatment modalities,including selective vasopressin receptor antagonists,for the management of hyponatremia in patients with cirrhosis.     

Pathophysiology and management of hypokalemia: a clinical perspective

Potassium (K(+)) ions are the predominant intracellular cations. K(+) homeostasis depends on external balance (dietary intake [typically 100 mmol per day] versus excretion [95% via the kidney; 5% via the colon]) and internal balance (the distribution of K(+) between intracellular and extracellular fluid compartments). The uneven distribution of K(+) across cell membranes means that a mere 1% shift in its distribution can cause a 50% change in plasma K(+) concentration. Hormonal mechanisms (involving insulin, β-adrenergic agonists and aldosterone) modulate K(+) distribution by promoting rapid transfer of K(+) across the plasma membrane. Extrarenal K(+) losses from the body are usually small, but can be marked in individuals with chronic diarrhea, severe burns or prolonged sweating. Under normal circumstances, the kidney's distal nephron secretes K(+) and determines final urinary excretion. In patients with hypokalemia (plasma K(+) concentration <3.5 mmol/l), after the exclusion of extrarenal causes, alterations in sodium ion delivery to the distal nephron, mineralocorticoid status, or a specific inherited or acquired defect in distal nephron function (each of which affects distal nephron K(+) secretion), should be considered. Clinical management of hypokalemia should establish the underlying cause and alleviate the primary disorder. This Review aims to inform clinicians about the pathophysiology and appropriate treatment for hypokalemia.     

Cirrhotic ascites review: Pathophysiology, diagnosis and management

Ascites is a pathologic accumulation of peritoneal fluidcommonly observed in decompensated cirrhotic states. Its causes are multi-factorial, but principally involve significant volume and hormonal dysregulation in the setting of portal hypertension. The diagnosis of ascites is considered in cirrhotic patients given a constellation of clinical and laboratory findings, and ultimately confirmed, with insight into etiology, by imaging and paracentesis procedures. Treatment for ascites is multimodal including dietary sodium restriction, pharmacologic therapies, diagnostic and therapeutic paracentesis, and in certain cases transjugular intra-hepatic portosystemic shunt. Ascites is associated with numerous complications including spontaneous bacterial peritonitis, hepato-hydrothorax and hepatorenal syndrome. Given the complex nature of ascites and associatedcomplications, it is not surprising that it heralds increased morbidity and mortality in cirrhotic patients and increased cost-utilization upon the health-care system. This review will detail the pathophysiology of cirrhotic ascites, common complications derived from it, and pertinent treatment modalities.     

Pathophysiology and management of unstable angina

Significant progress has been made in recent years in unraveling the dynamic mechanisms involved in the production of unstable angina. This knowledge, and advances in medical and interventional therapy allow the formulation of treatment strategies aimed at specific pathogenic mechanisms and promise to reduce mortality and morbidity. This review covers the diagnosis, pathogenesis, risk stratification, and therapy of unstable angina.     

Pathophysiology and management of pediatric ascites

Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the ‘underfill,’ ‘overflow,’ and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.     

Pathophysiology and management of primary immune thrombocytopenia

Primary immune thrombocytopenia, or idiopathic thrombocytopenic purpura (ITP), is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Autoantibodies against platelet surface glycoproteins, such as GPIIb/IIIa and GPIb/IX complexes, play major roles in both platelet destruction and impaired platelet production, although autoantibody-independent mechanisms, such as T cell-mediated cytotoxicity, may also be involved in its pathogenesis. Recent advances in the localization of autoantigenic epitopes and the characterization of T cell functional abnormalities in ITP patients have improved our understanding of the pathophysiology of this disease. Although corticosteroids and splenectomy remain central to the treatment of ITP, a new class of drugs, i.e., thrombopoietin receptor agonists (TPO-RAs) and rituximab, have substantially broadened the therapeutic options for refractory ITP patients. Moreover, the success of TPO-RAs in ITP patients shows that reduced platelet production caused by impaired megakaryocytopoiesis plays a greater role in ITP than previously recognized.     

Diabetes,hypertension, and cardiovascular derangements: Pathophysiology and management

Hypertension frequently coexists with diabetes mellitus, occurring twice as frequently in diabetic as in nondiabetic persons. It accounts for up to 75% of added cardiovascular disease (CVD) risk in people with diabetes, contributing significantly to the overall morbidity and mortality in this high-risk population. Patients with hypertension are two times more prone to have diabetes than are normotensive persons. Hypertension substantially increases the risk for coronary heart disease (CHD), stroke, retinopathy, and nephropathy. In patients with type 2 diabetes, hypertension usually clusters with the other components of the cardiometabolic syndrome, such as microalbuminuria, central obesity, insulin resistance, dyslipidemia, hypercoagulation, increased inflammation, and left ventricular hypertrophy (LVH). In type 1 diabetes, hypertension often occurs subsequent to the development of diabetic nephropathy. Hypertension in people with diabetes is characterized by volume expansion, increased salt sensitivity, isolated systolic blood pressure (BP) elevation, loss of the nocturnal dipping of BP and pulse, and increased propensity toward orthostatic hypotension and albuminuria. Among the treatment strategies tested in hypertensive diabetic persons, low-density lipoprotein (LDL)-cholesterol lowering to less than 100 mg/ dL and aggressive BP control to less than 130/80 mm Hg have proven effective in CVD risk reduction. The combination of two or more drugs is usually necessary to achieve the target BP.     

Pathophysiology and management of right heart ischemia

Acute right coronary artery occlusion proximal to the right ventricular (RV) branches results in right ventricular free wall dysfunction, exerting mechanically disadvantageous effects on biventricular performance. Depressed RV systolic function decreases transpulmonary delivery of left ventricular (LV) preload, resulting in diminished cardiac output. The ischemic right ventricle is stiff, dilated, and volume dependent, resulting in pandiastolic RV dysfunction and septally mediated alterations in LV compliance, which are exacerbated by elevated intrapericardial pressure. Under these conditions, RV pressure generation and output are dependent on LV-septal contractile contributions, governed by both primary septal contraction and paradoxical septal motion. When the culprit coronary lesion is distal to the right atrial (RA) branches, augmented RA contractility enhances RV performance and optimizes cardiac output. Conversely, more proximal occlusions result in ischemic depression of RA contractility, which impairs RV filling and performance, resulting in more severe hemodynamic compromise. Bradyarrhythmias limit output generated by the rate-dependent noncompliant ventricles. Hemodynamic compromise may respond to volume resuscitation and restoration of physiologic rhythm. Vasodilators and diuretics should generally be avoided. In some patients, parenteral inotropic stimulation may be required. The right ventricle appears to be relatively resistant to infarction and recovers even after prolonged occlusion. The term RV "infarction" appears to be somewhat of a misnomer, for in most patients acute RV dysfunction represents ischemic but predominantly viable myocardium. Although RV performance improves spontaneously even in the absence of reperfusion, recovery of function may be slow and associated with high in-hospital mortality. Reperfusion enhances recovery of RV performance and improves the clinical course and survival.     

Etiology and management of fecal incontinence

Fecal incontinence is a challenging condition of diverse etiology and devastating psychosocial impact. Multiple mechanisms may be involved in its pathophysiology, such as altered stool consistency and delivery of contents to the rectum, abnormal rectal capacity or compliance, decreased anorectal sensation, and pelvic floor or anal sphincter dysfunction. A detailed clinical history and physical examination are essential. Anorectal manometry, pudendal nerve latency studies, and electromyography are part of the standard primary evaluation. The evaluation of idiopathic fecal incontinence may require tests such as cinedefecography, spinal latencies, and anal mucosal electrosensitivity. These tests permit both objective assessment and focused therapy. Appropriate treatment options include biofeedback and sphincteroplasty. Biofeedback has resulted in 90 percent reduction in episodes of incontinence in over 60 percent of patients. Overlapping anterior sphincteroplasty has been associated with good to excellent results in 70 to 90 percent of patients. The common denominator between the medical and surgical treatment groups is the necessity of pretreatment physiologic assessment. It is the results of these tests that permit optimal therapeutic assignment. For example, pudendal nerve terminal motor latencies (PNTML) are the most important predictor factor of functional outcome. However, even the most experienced examiner's digit cannot assess PNTML. In the absence of pudendal neuropathy, sphincteroplasty is an excellent option. If neuropathy exists, however, then postanal or total pelvic floor repair remain viable surgical options for the treatment of idiopathic fecal incontinence. In the absence of an adequate sphincter muscle, encirclement procedures using synthetic materials or muscle transfer techniques might be considered. Implantation of a stimulating electrode into the gracilis neosphincter and artificial sphincter implantation are other valid alternatives. The final therapeutic option is fecal diversion. This article reviews the current status of the etiology and incidence of incontinence as well as the evaluation and treatment of this disabling condition.     

Anal incontinence: the role of medical management

BACKGROUND AND AIMS: Consensus recommendations suggest that patients with anal incontinence (AI) should be managed by medical treatment when indicated. Our aims were to prospectively evaluate from two different populations of patients: (1) the proportion of incontinent patients referred to a specialized center who were candidates for first line medical treatment (study 1); (2) the results of medical treatment in incontinent patients (study 2). METHODS: In study 1, standardized management of AI based on an algorithmic decision tree was applied to 287 incontinent patients (209 women, ranging from 16 to 84 years old). In study 2, 36 other incontinent patients with transit disorders (28 women, ranging from 29 to 86 years old) seen consecutively, were treated by a medical treatment of their transit disorders. The result of the medical treatment was objectively and subjectively evaluated after 2 months. RESULTS: Study 1: medical treatment was indicated in 126 of 287 patients (43.9%) (62 for diarrhea and 64 for constipation) while biofeedback was indicated in 52 patients (18.1%) and surgery specific for AI in 99 patients (34.5%). Eighty percent of the patients who were proposed conservative medical treatment were referred by their gastroenterologist or their general practitioner. Study 2: the continence score decreased from a median of 12 to 6.5 (P<0.001). 61% of patients regarded themselves as cured or improved after medical treatment. CONCLUSION: Conservative treatment can be proposed as a first line treatment in more than 50% of patients with anal incontinence referred to a specialized center. Medical treatment for anal incontinence associated with transit disorders improves continence.     

Pathophysiology, diagnosis, and management of dyslipidemia

Atherosclerosis is a systemic diffuse disease that may manifest as an anglographically localized coronary, cerebral, mesenteric, renal, and/or peripheral arterial stenosis or as diffuse atherosclerosis. While relief of organ ischemia is frequently possible with percutaneous or surgical revascularization, this in itself does not alleviate the long-term risks of disease recurrence or modify the metabolic derangements that promote atherosclerosis. It is critically important to recognize the need for treatment of dyslipidemia and to institute necessary therapies. The complex role of lipoprotein abnormalities is well understood and the use of lipid-lowering agents (90% statins) is reviewed in both primary and secondary prevention. The clinical interaction with novel risk factors and the practical problems in patient management are discussed.     

Pathophysiology and management of syncope in Kearns-Sayre syndrome

A 20-year-old woman with known Kearns-Sayre syndrome was transferred to the emergency department due to syncopal episodes. The electrocardiogram on admission showed complete atrioventricular block. The diagnosis of mitochondrial encephalomyopathy was made when she was 14 years old. At the time of the initial diagnosis, she displayed a normal electrocardiogram pattern. At the age of 17, electrocardiogram recordings demonstrated right bundle branch block with left anterior fascicular block and a prolonged QTc interval of 485 milliseconds (Figure). She was taking coenzyme Q10, oral nicotinamide adenine dinucleotide (reduced), piribedil, amantadine, and primidone. Transthoracic echocardiography revealed normal wall motion of both ventricles and mitral valve prolapse without regurgitation. A permanent dual-chamber pacemaker was immediately implanted.