Douglas Katz MD

• Assistant Professor of Surgery and Pediatrics, Jefferson Medical College,
• Philadelphia, Pennsylvania
• Attending Surgeon, Nemours/Alfred I. duPont
• Hospital for Children, Wilmington, Delaware

Rarely the sigmoid will have active Crohn disease with rigid thickening of the colonic wall and in such cases resection will be needed medicine over the counter trazodone 100 mg mastercard. If the sigmoid is resected medications 4 less canada order trazodone 100mg free shipping, primary anastomosis can usually be performed with or without temporary proximal diversion medications related to the lymphatic system order trazodone from india. The decision to perform proximal diversion should be based on the same factors discussed previously symptoms 5 days before your missed period generic trazodone 100 mg online. Enterovesical and Enteroureteral Fistulas Fistulas from the ileum medications nurses discount 100 mg trazodone fast delivery, colon medicine grace potter trazodone 100mg visa, or rectum to the genitourinary system occur at a rate of 1% to 8% in patients with Crohn disease. Unlike enteroenteric fistulas, these fistulas are usually symptomatic and rarely close without surgery. Patients usually present with dysuria, urinary urgency, urinary frequency, suprapubic discomfort, pneumaturia, or fecaluria after a well-established diagnosis of Crohn disease. The bladder dome is the most common site involved, and definitive treatment usually requires surgical therapy. First, the connection between the bladder and the intestine is divided and the diseased bowel is resected. A Foley catheter is left in place postoperatively (usually for 10 to 14 days) to drain the bladder and reduce tension on the repair. Symptoms include malodorous vaginal discharge and passage of air or stool from the vagina. Any decision to resect the involved genital organ should bear in mind the potential reproductive, endocrine, and sexual dysfunction that could occur. This is especially important in treating women of childbearing age and should be part of the informed consent discussion. The diseased small bowel is removed and anastomoses performed, unless a stoma is deemed necessary. The majority of enterocutaneous fistulas occur as postoperative complications, commonly draining through the surgical wound. Such fistulas are usually the result of anastomotic leaks but could be due to an unrecognized bowel injury. The natural history and treatment recommendations between these two types of fistula vary greatly. Immunomodulators and biologic agents may be of some benefit; however, operative intervention is frequently needed to achieve closure. It is important to note that operative therapy should not be delayed if there are complicating factors, such as distal obstruction, high fistula output, or difficult to manage wounds. In contrast, enterocutaneous fistulas secondary to surgical complications tend to respond well to conventional treatment of fistulae, especially if the involved bowel is intrinsically normal and not affected by active Crohn disease. Long, low-output fistulas are likely to close with nonoperative, conservative management, whereas short, high-output fistulae are more likely to require operative therapy. Percutaneous drainage of the abscess should be performed depending on the location of the abscess and the comfort of the interventional radiographer. It is most common in patients who present with concurrent toxic colitis, distal obstruction, or cancer or as a complication after surgical or endoscopic intervention. Patients who are on chronic immunosuppression, such as steroids, immunomodulators, and biologic therapy, might present with minimal symptoms. A plain abdominal radiograph might reveal free air and in some cases may be the only imaging study needed as the patient is best served by urgent laparotomy. In other cases, cross-sectional imaging may be appropriate to better define the disease process and to determine if urgent exploration is needed. Emergent surgical exploration is usually required when free perforation is suspected, and these patients should also receive adequate resuscitation, timely broad-spectrum antibiotics, and stress-dose steroids if appropriate. Prior to incision, the surgeon should mark the patient for possible stoma placement. Upon entry of the abdominal cavity, the source of perforation should be identified. Adequate resuscitation and source control are the goals of treatment in these patients. Abscesses Up to one-third of patients with Crohn disease will have an abscess at some point during their disease course. Unlike other surgical patients with abscesses, Crohn disease patients may have few symptoms due to their use of steroids, immunomodulators, and biologic agents. Proximal diversion with a loop or end stoma should be considered if the patient is on chronic immunosuppression, malnourished, or if the patient is hemodynamically unstable. Up to 80% of patients will have endoscopic evidence of disease recurrence 1 year after intestinal resection, and the majority of patients (60%) will have symptomatic recurrence 10 years after their initial operation. In patients with a diverting stoma, there is an increased likelihood that they will have a recurrence after intestinal flow is restored. Preventing disease recurrence is preferable to trying to treat active disease; therefore patients should undergo risk stratification and be treated with medical therapies appropriate to their risk profile. Postoperative therapy should be tailored to each individual patient based on the profile of their disease course. There are three risk categories that patients with Crohn disease fall into: low, intermediate, or high risk. It is imperative that patients are given clear follow-up instructions to ensure that treatment is monitored and modified based on clinical symptoms or endoscopic evidence of recurrence. In postoperative patients, the Rutgeerts score should be used to risk-stratify patients endoscopically over their postoperative course (Table 75. A Rutgeerts score less than 2 predicts a disease recurrence of less than 10%, whereas scores of 3 and 4 predict higher recurrence rates (50% or 100%). Patients with duodenal lesions present with symptoms of dyspepsia or epigastric pain, anorexia, and obstructive symptoms. Duodenal disease can include inflammatory lesions, strictures, and fistulas, and long-standing disease increases the risk of duodenal cancer. Because it is a rarer entity, medical treatment of duodenal Crohn disease is less well studied; however, recommendations are similar to those for more distal disease: (1) initiate medical therapy for active Crohn disease, (2) provide nutritional support, and (3) drain any abscess for source control usually via percutaneous approach. Duodenal fistulas should be approached by taking down the fistula tract, resecting the other diseased bowel, and then by addressing the duodenal opening. As such, closure of the duodenum after division of fistulas or stenosis operations should employ the Heineke-Mikulicz technique and, if needed, a bypass using a duodenojejunostomy, gastrojejunostomy, or Roux-en-Y anastomosis. Symptoms of acalculous obstructions include urinary frequency and urgency, flank pain, and fever. Axial imaging of the genitourinary system will reveal ureteral stenosis with upstream dilation. Treatment includes initiation of medical therapy for Crohn disease and ureteral stenting if a significant obstruction is present, as well as percutaneous drainage of any abscesses. Resection of the diseased bowel and ureterolysis should be performed if nonoperative management fails. The Rutgeerts endoscopic recurrence score also correlates with the likelihood of future clinical and surgical recurrence. Specifically, there are no clear benefits of routine use of nasogastric suction for distal procedures, and use of enteric suction in upper gastrointestinal operations is surgeon dependent. Another randomized trial of 24 patients found significantly less recurrence at 1 year on histologic and endoscopic examination with postoperative prophylactic infliximab. In addition, squamous cell carcinoma of the anus and skin, duodenal neoplasia, and testicular cancer are the most commonly reported cancers with increased incidence in the Crohn disease patient population. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Inflammatory bowel disease and smoking: a review of epidemiology, pathophysiology, and therapeutic implications. Environmental risk factors (excluding tobacco and microorganisms): critical analysis of old and new hypotheses. The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden. The distribution of ulcerative colitis and regional enteritis in United States veterans with particular reference to the Jewish religion. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Diagnostics and prognostics of inflammatory bowel disease with fecal neutrophil-derived biomarkers calprotectin and lactoferrin. Review article: practical management of inflammatory bowel disease patients taking immunomodulators. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Experimental inflammatory bowel disease: insights into the host-microbiota dialog. Heritability in inflammatory bowel disease: from the first twin study to genomewide association studies. Glucocorticosteroid therapy in inflammatory bowel disease: systematic review and meta-analysis. Home total parenteral nutrition: an alternative to early surgery for complicated inflammatory bowel disease. The Pfannenstiel or so called "bikini cut": still effective more than 100 years after first description. The low transverse Pfannenstiel incision and the prevalence of incisional hernia and nerve entrapment. Risk of cancer in inflammatory bowel disease: going up, going down, or still the same Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer. McFadden fistula is an abnormal communication between two epithelialized surfaces. Formerly, malnutrition and electrolyte imbalance were the major causes of death in affected patients. Currently, mortality is principally attributable to uncontrolled sepsis and its associated malnutrition. The majority (75% to 85%) of gastrointestinal fistulas are iatrogenic as a result of technical complications of surgical procedures and trauma. Etiologies include anastomotic dehiscence, intraoperative injury to the bowel or its blood supply, erosion from indwelling tubes, retention sutures or prosthetic mesh, and misplacement of a suture through the bowel during abdominal closure. Other complications that may cause a fistula include intraperitoneal bleeding and abscess formation with or without suture line dehiscence. The critical tenets in successful management of gastrointestinal fistulas are recognition of the fistula, control of infection and further contamination, restoration of fluid and electrolyte losses, and reestablishment of a positive nutritional balance before undertaking major definitive corrective procedures. Fluid and electrolyte abnormalities (hypovolemia, hypokalemia, hypomagnesemia, metabolic acidosis) are common and result from the sustained loss of intestinal fluid. Malabsorption and malnutrition from bacterial overgrowth may occur in gastrocolic or enterocolic fistulas. Local wound excoriation and discomfort from the intestinal effluent can thwart potential abdominal wall reconstruction and recovery after operation to repair a fistula. Finally, operating on a fistula before control of sepsis and nutritional optimization can lead to increased mortality and operative failure. Before 1950, greater than 60% mortality was observed in patients with gastric and duodenal fistulas, but in the 21st century the incidence has decreased to less than 3% and the mortality rate has decreased to less than 15%. Postoperative leaks from gastric staple or suture lines after ulcer surgery accounted for most perforations in the past. However, the decline in gastric resection for ulcer disease, along with the broad application of new endoscopic and laparoscopic techniques for other diseases, contributes to other newer causes of perforation, albeit at a lower incidence. Surgical Causes Any of the available gastric operations for morbid obesity may result in gastric staple line disruption in the early or late postoperative period. Early anastomotic or staple line leaks in this patient population are highly morbid and often lethal. For gastric bypasses, the 10% to 30% incidence rate of internal fistula formation after simple stapling has been reduced to 3% to 6% by either gastric division after stapling or up to three applications of the stapler without division. After total gastrectomy with Roux-en-Y esophagojejunostomy, anastomotic leaks occurred in 4. Sepsis is a recognized antecedent risk factor for the development of a gastrointestinal fistula, and the high metabolic requirement of the septic state can prevent spontaneous closure. Over the past half century, the mortality associated with gastrointestinal fistulas has decreased from 40% to 60% to approximately 15% to 20% of patients. This improvement in prognosis is attributable to advances in fluid and electrolyte/acid-base knowledge and therapy, blood administration, critical care, antibiotic regimens, and nutritional management. Careful attention must be paid to the physiologic, metabolic, and immunologic derangements in these patients. An organized and tolerant approach to the stabilization, investigation, planning and implementation of medical and surgical therapy, and healing phase should allow for a successful outcome in the majority of patients. Duodenal stump leakage has declined because of the decreased use of antrectomy for ulcer disease.

Should the recirculation be interrupted by resection of the terminal ileum treatment 2 lung cancer purchase cheapest trazodone and trazodone, or by primary ileal disease treatment works 100mg trazodone for sale, abnormally large losses of bile salts can occur medications bipolar disorder buy trazodone 100 mg amex. This situation increases bile salt production to maintain a normal bile salt pool medicine to calm nerves generic trazodone 100 mg mastercard. Similarly treatment 31st october 100mg trazodone sale, if bile salts are lost by an external biliary fistula treatment yeast infection home buy 100 mg trazodone mastercard, increased bile salt synthesis is necessary. However, except for those unusual circumstances in which excessive losses occur, bile salt synthesis matches losses, maintaining a constant bile salt pool size. During fasting, approximately 90% of the bile acid pool is sequestered in the gallbladder. Cholesterol Saturation Cholesterol is highly nonpolar and insoluble in water; thus it is insoluble in bile. Bile salts are amphipathic compounds containing both a hydrophilic and hydrophobic portion. In aqueous solutions, bile salts are oriented with the hydrophilic portion outward. Phospholipids are incorporated into the micellar structure, allowing cholesterol to be added to the hydrophobic central portion of the micelle. The concept of mixed micelles as the only cholesterol carrier has been challenged by the demonstration that much of the biliary cholesterol exists in a vesicular form. Structurally, these vesicles are made up of lipid bilayers of cholesterol and phospholipids. In their simplest and smallest form, the vesicles are unilamellar, but an aggregation may take place, leading to multilamellar vesicles. Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and phospholipids. In a solution composed of 10% solutes similar to bile, the area under the curve represents the concentration at which cholesterol is maintained in solution. In the area above the curve, bile is supersaturated with cholesterol, and precipitation of cholesterol crystals can occur. A mathematical model of cholesterol solubility has been developed and is influenced by the relative concentrations of lipid components and the total lipid composition. Gallstones form as a result of the imbalance in concentration of solutes within the bile (bilirubin, bile salts, phospholipids, and cholesterol). After the bile is saturated, it precipitates into a more solid component: gallstones. Gallstones can be differentiated according to their composition into cholesterol and pigment stones. Cholesterol stones are usually multiple, of variable size, and irregular with color range from clear yellow to green and black. Pigment stones are dark due to the presence of calcium bilirubinate and only 20% of cholesterol. Black pigment stones are small and black, often formed as a consequence of hemolytic diseases such as hereditary spherocytosis and sickle cell disease. Cholesterol stones are more prevalent in Western countries (>85%), mostly due to obesity. Brown-pigmented stones are predominant in Asia primarily as a result of bacterial infections, biliary parasites, and stasis from partial biliary obstruction. The tetrahedral plot is used to record the relationships of the four major constituents of bile: water, bile salts, lecithin, and cholesterol. The triangular coordinates can be divided into four zones, representing the physical state of the solutes in bile: crystals of cholesterol plus liquid (A); cholesterol crystals plus cholesterol liquid crystals plus liquid (B); liquid crystals plus liquid (C); and the micellar zone in which cholesterol is in water solution through the formation of cholesterol-lecithinbile salt micelles (D). Phospholipids are transferred more efficiently than cholesterol, leading to cholesterol enrichment of the remaining (remodeled) vesicles. Aggregation of these cholesterol-rich vesicles forms multilamellar liquid crystals of cholesterol monohydrate. The remaining 15% to 20% is derived largely from the breakdown of hepatic hemoproteins. Although both may be important physiologically, the microsomal enzyme heme oxygenase, found in high concentration throughout the liver, spleen, and bone marrow, plays a major role in the initial conversion of heme to biliverdin. Bilirubin is bound avidly to plasma proteins, primarily albumin, before uptake and further processing by the liver. The liver is the sole organ capable of removing the albumin-bilirubin complex from the circulation and esterifying the potentially toxic bilirubin to water-soluble, nontoxic monoconjugated and deconjugated derivatives. After being extracted by the hepatocytes, bilirubin is conjugated with glucuronic acid to form bilirubin diglucuronide (conjugated bilirubin). The enzyme responsible for this reaction is glucoronil transferase present in the endoplasmic reticulum of the hepatocyte. Bilirubin is then transported within the hepatocyte by cytosolic binding proteins, delivering the molecule to the canalicular membrane for active secretion into bile. Conjugated bilirubin is then excreted into the duodenum in association with mixed lipid micelles. Once in the intestine, bilirubin is converted to urobilinogens by intestinal bacteria, which are then further oxidized to pigmented urobilins. To serve this overall function, the gallbladder has absorptive, secretory, and motor capabilities. As a result the gallbladder stores concentrated bile that reenters the distal bile duct and is secreted into the duodenum in response to a meal. The resultant mucin gel is believed to constitute an important part of the unstirred layer (diffusion-resistant barrier) that separates the gallbladder cell membrane from the luminal bile. However, considerable evidence also suggests that mucin glycoproteins play a role as pronucleating agents for cholesterol crystallization. Bile is usually concentrated fivefold by the absorption of water and electrolytes. The concentration of calcium in gallbladder bile, which is an important factor in gallstone pathogenesis, is influenced by serum calcium, hepatic bile calcium, gallbladder water absorption, and the concentration of organic substances, such as bile salts in gallbladder bile. The solubility in the micellar fraction is increased, but the stability of phospholipid-cholesterol vesicles is greatly decreased. Because cholesterol crystal precipitation occurs preferentially by vesicular rather than micellar mechanisms, the net effect of concentrating bile is an increased tendency to nucleate cholesterol. However, the absorption of bilirubin, cholesterol, phospholipids, and bile salts is minimal compared with that of water. Thus these organic compounds are significantly concentrated by the normal absorptive process that occurs in the gallbladder. The arrows indicate the route of water flow across the cell membrane and into the intercellular spaces. Sodium chloride is pumped into the intercellular space, and the result is a hypertonic environment. As water is transported into the space, the space distends, and an isotonic solution enters the connective tissue space. Prostaglandins play an important role as stimulants of gallbladder mucin secretion. Furthermore, mucin glycoproteins are key pronucleating agents for cholesterol crystallization. The acidification of bile occurs by the transport of hydrogen ions by the gallbladder epithelium, through a sodium-exchange mechanism. Acidification of bile promotes calcium solubility, thereby preventing its precipitation as calcium salts. Compared with gallbladder bile, the bile secreted by the liver is slightly alkaline, pH 7. However, the gallbladder does not simply fill passively and continuously during fasting. When stimulated by eating, the gallbladder empties 50% to 70% of its contents within 30 to 40 minutes. Many other hormonal and neural pathways are also necessary for the coordinated action of the gallbladder and sphincter of Oddi. Defects in gallbladder motility, which increase the residence time of bile in the gallbladder, play a central role in the pathogenesis of gallstones. Endoscopic sphincterotomy: follow-up evaluation of effects on the sphincter of Oddi. The sphincter regulates the flow of bile and pancreatic juice into the duodenum and also prevents the regurgitation of duodenal contents into the biliary tract. These functions are achieved by keeping pressure within the bile and pancreatic ducts higher than duodenal pressure. Thus sphincter pressure relaxes after a meal, allowing the passive flow of bile into the duodenum. During fasting, high-pressure phasic contractions of the sphincter of Oddi persist through all phases of the migrating myoelectric complex. Variations in origin and course of the hepatic artery and its branches: importance from a surgical viewpoint. Intestinal diffusion barrier: unstirred water layer or membrane surface mucous coat Recent progress in understanding cholesterol crystal nucleation as a precursor to human gallstone formation. Interdigestive biliary output in man: relationship to fluctuations in plasma motilin and effect of atropine. This activity may be a preventive mechanism against the accumulation of biliary crystals during fasting. The gross anatomy and histology of the gallbladder, extrahepatic bile ducts, vaterian system, and minor papilla. The hepatic, cystic, and retroduodenal arteries and their relations to the biliary ducts with samples of the entire celiacal blood supply. The cystic artery and constituents of the hepatic pedicle: a study of 500 specimens. Practical classification of the branching types of the biliary tree: an analysis of 1094 consecutive direct cholangiograms. A thorough evaluation of a patient with obstructive jaundice includes detailed medical and surgical history, physical examination, laboratory data, and evaluation of pertinent imaging. A multidisciplinary approach including the primary care physician, surgeon, gastroenterologist, and interventional radiologist provides comprehensive management options. Noninvasive imaging studies provide the foundation for treatment planning, including surgical and/or percutaneous intervention. Percutaneous biliary interventions may be the primary diagnostic and therapeutic treatment option or serve as a conduit for later surgical intervention. The principal objectives of the chapter include (1) reviewing the role of noninvasive imaging modalities commonly used in the patient presenting with biliary obstruction and (2) examining the role of minimally invasive percutaneous interventions available for the patient with either benign or malignant biliary disease. The goals of imaging are to not only confirm the presence of obstructive jaundice but also to define the biliary anatomy. In the case of a malignant etiology, imaging can also stage the extent of disease. These techniques, as well as other interventions, including percutaneous biopsy, drainage catheter management, percutaneous biliary stricture dilatation, and biliary endoprostheses, are reviewed. The appropriate selection for each approach, as will be discussed, depends on the clinical scenario and etiology of the stricture, whether it be benign, malignant, or iatrogenic. The goal of the chapter is to provide readers with a basic understanding of the role of imaging and imageguided intervention for the patient with complex biliary conditions. The normal gallbladder is an ovoid, anechoic, fluid-filled structure adjacent to the interlobar fissure, which separates the right and left hepatic lobes. The cystic duct is normally located posterior to and may join with the common hepatic duct at variable distances, forming the common bile duct. In 10% of the population the cystic duct runs parallel to the common hepatic duct for a long segment, where it is joined by a fibrous sheath, which may cause the common hepatic duct to be misinterpreted as the cystic duct. The hepatic artery separates the common hepatic duct from the portal vein within the hepatoduodenal ligament. However, in 10% to 15% of the patients, the hepatic artery is located anterior to the common hepatic duct. The common bile duct travels toward the second portion of the duodenum as it adopts a more posterior position. The principal objectives of the chapter include (1) reviewing the role of noninvasive imaging modalities commonly used in the patient presenting with biliary obstruction, and (2) examining the role of minimally invasive percutaneous interventions available for the patient with either benign or malignant biliary disease. Unenhanced scans provide a baseline to determine lesion enhancement and to better detect stones, which can be obscured by contrast material. When there is concern for malignancy, a late arterial phase may be obtained at 45 to 50 seconds. In addition to assessing vascularity within a tumor, a late arterial phase allows for detection of vascular involvement surrounding the tumor, which may alter or preclude surgical management. A 10-minute delayed scan should be added when there is suspicion for cholangiocarcinoma because these tumors often demonstrate delayed enhancement relative to the remainder of the hepatic parenchyma. A thin section technique (1 mm or less) allows for higher quality multiplanar reformats. The common hepatic duct and common bile ducts appear as tubular water density structures with near imperceptible walls. The distal common bile duct takes on a round or oval configuration at the level of the pancreatic head. The color Doppler scan (B) helps to differentiate dilated ducts from hepatic vessels.

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These factors may lead to increased morbidity and mortality in the severely ill recipient treatment goals for ptsd buy generic trazodone 100 mg line, and split grafts should be used sparingly in this group medicine zyprexa cheap trazodone 100 mg. Because of its prevalence as an indication for transplantation medications 4 times a day order trazodone australia, its propensity to reinfect the new allograft medicine side effects trazodone 100mg lowest price, and our relatively ineffectual ability to treat in the posttransplant setting medications 5 rights buy trazodone amex, recurrence of hepatitis C is a significant problem facing liver transplant physicians xerostomia medications that cause trazodone 100 mg for sale. An unfortunate unpredictable subgroup will manifest early aggressive recurrence, often leading to graft failure within the first year. Hepatitis B activation, once common after transplant, is now rare because of improved antiviral regimens. Its purpose is to maintain the data from all solid organ transplant centers and perform large-scale analyses that are available to professionals and to the general public and transplant candidates. Their reports provide crucial collections of evidence on which the transplant community-including policy makers-makes informed decisions on topics such as procurement and allocation. Similarly, graft survival, which is the percentage of grafts still functioning at 1 month, 1 year, and 3 years is 95. From an experimental procedure just 35 years ago, this operation is now performed over 6000 times per year in the United States with remarkable outcomes. Continued efforts are needed in the areas of donor pool expansion, the treatment of fatty liver disease, management and transplant of the intensive care unit patient, and further refinement of the selection process for high-risk cancer patients. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. Nonalcoholic fatty liver: optimizing pretransplant selection and posttransplant care to maximize survival. Liver transplantation for non-hepatocellular carcinoma malignancy: indications, limitations, and analysis of the current literature. Department of Health and Human Services: Organ Procurement and Transplantation Network. A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. Data only include first-time isolated liver transplants (redo and multiorgan transplants excluded). Transplantation in the hepatitis B patient and current therapies to prevent recurrence. Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease. The organ center of the United Network for Organ Sharing and twenty years of organ sharing in the United States. Back-table arterial reconstructions in liver transplantation: single-center experience. Veno-venous bypass without systemic anticoagulation for transplantation of the human liver. Efficacy and safety of heat exchanger added to venovenous bypass circuit during orthotopic liver transplantation. Postreperfusion syndrome: hypotension after reperfusion of the transplanted liver. A cost-effectiveness analysis of biliary anastomosis with or without T-tube after orthotopic liver transplantation. Plasmapheresis: an effective therapy for primary allograft nonfunction after liver transplantation. Ischemic arterial complications after liver transplantation in the adult: multivariate analysis of risk factors. Cytomegalovirus and its association with hepatic artery thrombosis after liver transplantation. Causes of early acute graft failure after liver transplantation: analysis of a 17-year single-centre experience. Risk factors for and clinical course of non-anastomotic biliary strictures after liver transplantation. Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Randomized controlled trial of sequential intravenous and oral ganciclovir versus prolonged intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in high-risk cytomegalovirus-seronegative liver transplant recipients with cytomegalovirus-seropositive donors. Incidence of death and potentially life-threatening near-miss events in living donor hepatic lobectomy: a world-wide survey. Nyberg he failing liver represents a syndrome with profound morbidity and mortality. The morbidity of liver failure is secondary to the tremendous decline in metabolic and synthetic functions inherent to the liver. Cerebral edema (the most feared complication) is strongly associated with elevated levels of ammonia. One of the leading synthetic functions of the liver is the production of coagulation factors. In addition, the liver is home to an abundant source of resident macrophages, Kupffer cells,2,3 which are believed to produce cytokines leading to systemic inflammation in the setting of the failing liver. Patients suffering from a failing liver have the possibility of recovering spontaneously. However, for the patients who are not likely to recover spontaneously, the only proven treatment is liver transplantation. Before liver transplantation, the mortality rate of patients with acutely failing livers was greater than 80%. More importantly, there is shortage of livers for patients on the transplant waiting list. After glutathione is depleted from hepatocytes, a centrilobular pattern of hepatocyte necrosis ensues. Even with liver transplant and modern intensive care, mortality is still as high as 30%. However, with numerous disadvantages of liver transplantation, such as organ shortage and requirement of life-long immunosuppression, alternative therapies have been sought after by researchers. Liver support systems are one of the most studied alternative therapies, and many of them have reached clinical trial stage. Liver support systems can be further categorized into artificial and bioartificial support systems; bioartificial systems incorporate active hepatocytes to provide further liver function support. One of the main aims of future studies is to develop a reliable method to mass produce hepatocytes for therapy and research purposes. However, group 2 (acute decompensation) and group 3 (acute liver failure) are recognized by those that lead to hospitalization. Unfortunately, approximately 35% of the acute liver failure group and 20% of the acutely decompensated group die as a result of their failing liver. Antimicrobials (46% of total cases), especially antituberculosis medications, are the most commonly implicated offenders. This study included consecutive resections ranging from nonanatomic wedge resections to extended hepatectomies (up to six segments). The incidence of failure was not listed for the number of segments resected; however, 583 patients had five or six segments resected. Of the 301 patients receiving extended right hepatectomy, 44 patients were determined to have liver insufficiency following resection. After being recognized, coordination is a necessity between primary care and referral centers and medical and surgical disciplines at the referral center. Quality intensive care aims to counteract hemodynamic instability and prevent extrahepatic manifestation of liver failure, including cerebral edema, and potentially allow for recovery or sufficient time for transplant. These patients should have routinely scheduled scoring of their mental status (Glasgow Coma Scale, Full Outline of Unresponsiveness score). Nutrition (enteral or parenteral) should be initiated at this juncture to maintain intake of calories, prevent hypoglycemia, stabilize ammonia production, and assist in healing the injured liver. The patient should have the head of the bed elevated to 30 to 45 degrees, minimal stimulation from lighting and noise, and sedation with propofol. Periodic cultures are recommended with prompt treatment at earliest signs of infection. Although not proven to improve overall outcome, prophylactic antibiotics (antibacterial, antifungal, and antiviral) may be considered due to high infection rates and future possibility of further immunosuppression should transplantation occur. After urea and ornithine are produced from arginine, the urea diffuses out of the hepatocyte and ornithine is transported back into the mitochondria to continue the cycle. The ideal liver support system would detoxify blood to physiologic levels, accomplish all hepatic synthetic functions, attenuate systemic inflammation, and allow for the regenerative capacity of the liver. Ammonia accumulation correlates with the most feared complication of the acutely failing liver, cerebral edema. During the development of a potentially successful liver support system, investigators should take effort in demonstrating urea cycle function not only by measuring levels of urea production and ammonia removal but also by showing effective levels of urea cycle gene expression by hepatocytes in the liver support device. Two important synthetic functions of the liver are production of albumin and coagulation proteins. Albumin production serves as a useful marker of liver-specific protein production in support systems using hepatocytes. Coagulation pathway restoration is an important part of the ideal liver support system. An effective coagulation pathway profile by a bioartificial liver not only prevents bleeding complications but also reduces the use of transfused blood products, avoids complications of their use, and saves resources for other patient populations. In the setting of a bioartificial liver support system, this concept of controlling the flow rate can be demonstrated in two models (the diffusion model and the convection model). The diffusion model considers the transfer of waste molecules and product molecules across a semipermeable membrane according to concentration gradients of these molecules. The top model is based upon diffusion- molecules filter from high concentration to low concentration. The bottom model relies on pumps (convection) to allow for increased filtration of larger molecules. Both models contain a semipermeable membrane that allows for passage of nonimmunologic molecules. Toxins from the patient are metabolized, and proteins are synthesized within the hepatocyte compartment and returned back to the patient. The convection model incorporates pumps that force flow across the semipermeable membrane and allow for a theoretical advantage of increased passage of larger toxins and liver-synthesized proteins into and out of the hepatocyte compartment. Under these conditions, ammonia, direct and indirect bilirubin, tumor necrosis factor, and albumin were shown to cross the membrane at high rates. Equally important, immunoglobulin G (IgG) and IgM were shown to cross at negligible levels, thus significantly reducing the risks of cytotoxic effects. There are two current types of liver support systems, artificial and bioartificial systems. Historical examples of artificial liver support include charcoal hemoperfusion and hemodialysis. Plasma exchange/hemodiafiltration involves a combination of two detoxification methods. The second, hemodiafiltration (a combination of hemodialysis and hemofiltration), washes the plasma in high volumes of dialysate and aids in the removal of toxins, such as ammonia. This combined method of artificial liver support is most commonly used in Japan secondary to the low number of cadaveric organ donations performed in that country. The overall survival was 42% (5 of 12), with seven patients dying from lack of donor livers. The third circuit then allows for removal of water-soluble toxins from the second albumin circuit. The study showed no statistical significance in 6-month and 1-year overall survival. The fractionated plasma (containing albumin) is then passed over two adsorption columns, allowing for direct detoxification of the albumin. Overall, no survival advantage was demonstrated between the groups at either 28 days or 90 days following initial treatment. The ideal bioartificial liver support system would use human hepatocytes; however, a good-quality source of large numbers of human hepatocytes is currently not available. Most human hepatocytes currently come from unused cadaveric donors (discarded because of poor quality) or from nondiseased partial hepatectomy specimens, which are relatively uncommon. Good-quality donor livers are not available because they are in great demand for use in liver transplantation. Novel solutions to expand the availability of human hepatocytes will be discussed later in this chapter. This device allows for hemoperfusion from the patient through columns containing immortalized C3A cells. By use of ultrafiltration, toxins can be detoxified and synthesized proteins can return to the patient. The device contains two acellular membranes to prevent the spread of hepatoblastoma cells back to the patient. However, this device was composed of a single cartridge containing 100 g of HepG2/C3A cells. Groups were stratified based upon who met criteria for transplantation and who did not. There was also no difference between the groups when they were further separated based upon meeting or not meeting transplantation criteria. No significant change in overall survival was observed between the treatment group and control group at 28 and 91 days. The largest trial to date using HepatAssist device was published by Demetriou et al. On further analysis, 147 of the 171 patients enrolled suffered from fulminant or subfulminant hepatic failure. Thus the ideal therapy should either increase the likelihood of spontaneous recovery or effectively serve as a bridge to transplant with the ultimate goal of improved survival. Cellular transplantation of 107 to 1010 allogeneic hepatocytes has also been tested as therapy for human liver failure with modest results.

As little as 20% to 25% of the nutrition supplied enterally is usually sufficient to provide the advantages of enteral nutrition medications for factor 8 purchase 100mg trazodone, and the remainder can be supplied via parenteral nutrition medications definitions order genuine trazodone. In addition to this adjunctive role with parenteral nutrition symptoms at 4 weeks pregnant buy trazodone 100mg without prescription, tube feeding continues to be an important measure in the complete nutritional management of some fistula patients with distal and low-output fistulas medicine abbreviations purchase trazodone 100mg visa, when the fistulas are nearly healed medicine 79 order trazodone 100 mg mastercard, or when parenteral nutrition is difficult or impossible to institute medicine journal impact factor purchase trazodone 100 mg mastercard. Normal intestinal motility and function generally return once abdominal sepsis is controlled and fluid and electrolyte imbalances are corrected. If the fistula location is such that enteric access and alimentation are possible, enteral nutrition can be instituted and parenteral nutrition phased out. Control of Sepsis (and Control of Fistula Effluent) Uncontrolled sepsis remains the major factor contributing to mortality in patients with small intestinal fistulas. Aggressive management of ongoing infections and careful surveillance for new septic foci are necessary for successful management. Tachycardia, persistent fever, and leukocytosis predict inadequate control of the fistula or abscess formation. Malnutrition in the presence of uncontrolled sepsis cannot be treated without effective drainage of the septic source. Typically, drainage of an intraabdominal abscess is required, which is ideally accomplished in an image-guided, percutaneous fashion. In addition, fistula drainage must be controlled and the skin of the abdominal wall protected. Local control is an extremely important component of the early management of a fistula. Discontinuation of oral intake and initiation of parenteral nutrition are important first steps. Suction aspiration via placement of a nasogastric tube or a nasoenteric tube positioned proximal to the fistula may be helpful with enteric fistulas involving the duodenum or proximal jejunum. Fistulas that have been controlled with a tube should cause minimal injury to fascia, subcutaneous tissue, and skin. Such injuries typically include perforations with abscesses that have been percutaneously drained or have been converted at surgery to a controlled fistula with an indwelling tube or an adjacent drain. Drainage should be collected to measure the output and provide guidance for fluid and electrolyte replacement. Precautionary steps should be instituted early because once excoriation is present, healing is difficult in the presence of ongoing drainage. A fistula should be exteriorized on a flat portion of the abdominal wall with avoidance of bony prominences and skin folds. This permits secure application of an ostomy bag or other device to collect and monitor fluids and protect the skin. Specialized nursing assistance by an enterostomal therapist or wound care specialist is necessary in the management of these complex wounds. Drainage with a single catheter placed into the site generally fails because the catheter becomes occluded or the volume of fluid expelled with peristalsis exceeds the capacity of the catheter. In some instances, a sump suction catheter can be placed through the external opening and gentle continuous suction applied to control fistula drainage. Two 18-French or larger catheters with multiple side perforations are tied together and passed into the fistula through the open end of the bag. A third 18-French catheter with multiple perforations is placed in the ileostomy bag, and the open end of the bag is tied securely around all three catheters. One of the two catheters within the fistula and the catheter lying free in the bag are set for continuous suction at a minimum of 40 mm Hg of negative pressure. When functioning, the bag is completely collapsed, and fluid leaking from the tract is immediately aspirated away. The surrounding skin can be protected with Stomahesive paste, karaya gum powder, aluminum paste, tincture of benzoin, or zinc oxide/menthol cream. Once intraabdominal sepsis is present, the use of antibiotics does not eliminate the need for surgical treatment or percutaneous drainage. If possible, general anesthesia and major surgical procedures should be avoided or postponed until the patient is stabilized. Abdominal exploration may be required in septic patients who are losing ground, even if diagnostic studies have not pinpointed an abscess. In the rare case that exploratory laparotomy is required for drainage, one should avoid the temptation of definitive repair of the fistula, as it is prone to failure. In addition, such failure may make subsequent attempts more difficult and possibly result in infection of previously uninvolved areas of the abdomen. Control of the fistula should be established during the operation by allowing complete drainage to the skin surface or by exteriorizing the fistula. Sputum, urine, wound, and blood cultures, including those from central venous lines, should also be obtained. After sepsis is controlled, parenteral/enteral nutrition should result in improved nutritional status, allow skin lesions to heal, and the future operative field to become quiescent. Even if the regimen of bowel rest in conjunction with intravenous and enteral nutrition does not lead to successful spontaneous fistula closure, the patient is generally in better nutritional and metabolic condition to tolerate a definitive operation. Pharmacologic Support the concept of using somatostatin to inhibit pancreatic exocrine secretion in the treatment of gastrointestinal fistulas was first introduced in 1979 by Klempa et al. An inhibitory effect on gastric, biliary, and pancreatic secretions is generally observed in clinical use. It has been suggested that if fistula output is not decreased within 48 hours of treatment with somatostatin-14 or octreotide, then treatment should be discontinued. These medications may be useful in decreasing fistula output, particularly with proximal fistulas or when gastric secretion is high. Other agents that are helpful in reducing intestinal transit times and decreasing intestinal volume losses include antiperistaltic agents such as loperamide at a dose of 8 to 16 mg/day or more, diphenoxylate at 10 to 20 mg/day or more, paregoric at 20 to 40 mL/ day, or tincture of opium at 2. Most failures of these medications occur when suboptimal doses are used by practitioners and, in the case of patients attempting oral nutrition, when medications are timed incorrectly. Patients with refractory fistulas related to Crohn disease have been successfully treated with short courses of cyclosporine and other immunosuppressive drugs. In five patients with a total of 12 fistulas, Hanauer and Smith used an infusion of 4 mg/kg per day for 6 to 10 days, followed by oral dosing at 8 mg/kg per day adjusted to maintain serum cyclosporine levels of 100 to 200 ng/ mL. Therapy was continued for a mean of 6 months, with five recurrences, two of which were related to inadequate cyclosporine serum levels. In the past decade, infliximab, a chimeric monoclonal antibody to tumor necrosis factor-, was developed as treatment for Crohn disease. In a randomized, multicenter trial investigating infliximab administered intravenously at 0, 2, and 6 weeks and dosed at 5 mg/ kg for the treatment of 94 adult Crohn disease patients with chronic fistulas, partial resolution of multiple lesions occurred in 68% and complete closure occurred in 55% of patients. Stabilization is accomplished in the first 24 to 48 hours; investigation usually occurs over the following 7 to 10 days. Investigation includes a thorough evaluation of the gastrointestinal tract, definition of the anatomy of the fistula, and identification of any complicating features such as abscess, stricture, or distal obstruction. Early on, oral administration of indigo carmine or charcoal can be used to demonstrate the presence of a connection between the gastrointestinal tract and the abdominal wall or urinary bladder. These tests prove only the presence of a fistula and do not identify its site or source. Probably the most important first test is a fistulogram, which will define the length and width of the fistula, as well as its anatomic location. It is best performed by the responsible surgeon in collaboration with the radiologist. The value of the procedure is enhanced by close involvement of the surgeon and the radiologist as the study is performed. Fistulography performed early in the course of the disease will help to determine (1) the site of the fistula, (2) intestinal continuity with the fistula, (3) the presence or absence of distal intestinal obstruction, (4) the nature of the intestine immediately adjacent to the fistula, and possibly (5) the presence or absence of an intraabdominal abscess. Fistulography should be followed by a complete contrast study of the gastrointestinal tract either orally or through existing intraluminal tubes. Such study is valuable both for identifying the internal source of the fistula, the presence of additional fistulas, and for defining its size and complicating factors such as distal obstruction. These tests can define the anatomy of the vicinity of the fistula and evaluate for any ongoing or unrecognized intraabdominal processes or abscesses, as well as distal obstruction. Injection of a cutaneous fistula demonstrates several tracts (arrows) leading to the ileum. If found, significant fluid collections should be drained and an indwelling catheter left in the cavity. This permits subsequent examination of the cavity under fluoroscopy with water-soluble contrast to assist in delineation of the fistula tract. Although the site of perforation may not be identified on initial injection because of inflammation, subsequent examinations after several days of drainage will often show the site of the fistula. However, endoscopy is not usually advisable if an acute perforation is suspected and should generally be delayed until the acute inflammatory process has resolved. Endoscopic examination of the stomach and duodenum may occasionally be used to identify a fistulous source and to take biopsy samples of adjacent tissue for exclusion of malignancy. For suspected gastrocolic or duodenocolic fistulas, colonoscopy may identify the involved site and enable a biopsy to be performed to diagnose inflammatory bowel disease or malignancy. Two recent large studies also have shown the therapeutic benefit of endoscopic fistula management. Morbidity and mortality rates are only increased by a delay under these circumstances. Diagnostic laparoscopy may be useful to rule out perforation after a previous laparoscopic procedure or after an endoscopic procedure. It is not usually appropriate in a septic, hypotensive patient and does not enable a satisfactory examination of the retroperitoneal duodenum. Early laparoscopy for tachycardia or unexplained fever is essential to prevent mortality from an anastomotic leak after gastric bypass surgery. When making these decisions, the likelihood of spontaneous closure must be estimated. In general, anatomic locations that are favorable for closure are the oropharynx, esophagus, duodenal stump, pancreas, biliary tree, and jejunum. Alternatively, unfavorable locations include the stomach, lateral duodenum, ligament of Treitz, and the ileum. Patients with poor nutritional status are much less likely to close a fistula no matter what the anatomic location. The absence of sepsis has a positive predictive value for closure, whereas the converse is true in the presence of sepsis. Postoperative fistulas and fistulas secondary to appendicitis or diverticulitis are likely to close. Fistulas associated with cancer will usually require excision of the tumor along with the fistula. In addition, the presence of a foreign body will prevent closure of the fistula without operative intervention. After sepsis has been controlled and diagnostic studies have been completed, management of a fistula should follow a conservative course. It is important to provide adequate nutritional support and to aggressively investigate any new onset of signs of sepsis during this convalescent period. If a positive nitrogen balance is maintained, fistula output decreases, and no septic complications develop, nonoperative management may be continued. Less than 10% closed after 2 months, and none closed spontaneously after 3 months. Thus a reasonable management plan may consist of at least 1 month of nonoperative management, with reasonable extensions should the fistula show signs of slow but continued healing. Delaying operation allows peritoneal reaction and inflammation to subside, thus making a definitive surgical procedure easier and safer. Delaying repair also permits nutritional optimization, thereby decreasing the likelihood of postoperative wound complications. In fact, many patients are candidates for discharge home or to a skilled nursing facility during the convalescent period because of the availability of these agents in such settings. The condition of the bowel or other organs involved in the fistula is also important. Healthy adjacent tissue is a favorable factor, as are small fistulas, quiescent disease, and the absence of an abscess. Total disruption of the bowel negates closure, as does distal obstruction, abscess, malignancy, irradiation (or both), epithelialization of the fistula tract, and active disease. Typically, a long fistula tract (longer than 2 cm) is more likely to close than a short fistula tract. Fistulas associated with a concurrent pancreatic fistula also have a low rate of spontaneous closure, as do those occurring in the presence of malnutrition or adjacent infection. Vigorous attempts to identify each of these confounding factors and to modify their influence may increase the success of nonoperative strategies, but operative intervention is generally necessary when they are present. General wisdom holds that a fistula that has not closed by 4 to 6 weeks is unlikely to do so and operation is indicated. A constant fear of leakage from the fistula appliance, being dependent on intravenous fluids and being dependent on health care professionals caused isolation and social restriction. The most favorable time to reoperate on patients is either within 10 days of diagnosis or after 4 months. If medical therapy is undertaken for a small, contained perforation, close monitoring should be performed with surgical exploration initiated within 24 hours for perforations that do not improve or that worsen. With both laparoscopic and open procedures, anastomotic leaks will frequently occur later, approximately 1 week after surgery. The decision to operate will be influenced by the ability to drain associated abscesses percutaneously and the presence of peritonitis. Focal collections that are adequately drained with a good systemic response and only local tenderness may continue to be observed for eventual closure.