George M. Kushner, DMD, MD

• Professor of Oral and Maxillofacial Surgery
• University of Louisville School of Dentistry
• Louisville, Kentucky

A prospective study of gall stone patients before and two years after surgery medicine evolution thyroxine 125 mcg order on-line, Gut 28(11):1500­1504 treatment question purchase thyroxine 100 mcg mastercard, 1987 medications covered by medicaid discount 200 mcg thyroxine visa. A critical reappraisal 15 years after the introduction of laparoscopic cholecystectomy medicine man dispensary generic thyroxine 200 mcg with mastercard, Dig Dis Sci 52(5):1313­1325 medications hyponatremia purchase cheapest thyroxine, 2007. Sanjay P, et al: A 5-year analysis of readmissions following elective laparoscopic cholecystectomy-cohort study, Int J Surg 9(1):52­54, 2011. Sarkut P, et al: Gallbladder polyps: factors affecting surgical decision, World J Gastroenterol 19(28):4526­4530, 2013. A retrospective analysis of 10,174 laparoscopic cholecystectomies, Surg Endosc 12(4):305­309, 1998. Sciarretta G, et al: Use of 23-selena-25-homocholyltaurine to detect bile acid malabsorption in patients with illeal dysfunction or diarrhea, Gastroenterology 91(1):1­9, 1986. Sherman S, et al: Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter, Gastrointest Endosc 36(5):462­466, 1990. Sostre S, et al: A noninvasive test of sphincter of Oddi dysfunction in postcholecystectomy patients: the scintigraphic score, J Nucl Med 33(6):1216­1222, 1992. Southern Surgeons Club: A prospective analysis of 1518 laparoscopic cholecystectomies, N Engl J Med 324(16):1073­1078, 1991. Endoscopic sphincterotomy or common bile duct exploration, Ann Surg 213(6):627­633, discussion 633­634, 1991. Stefaniak T, et al: Psychological factors influencing results of cholecystectomy, Scand J Gastroenterol 39(2):127­132, 2004. Stewart L, et al: Right hepatic artery injury associated with laparoscopic bile duct injury: incidence, mechanism, and consequences, J Gastrointest Surg 8(5):523­530, discussion 530­531, 2004. Factors that influence the results of treatment, Arch Surg 130(10):1123­1128, discussion 1129, 1995. Tantia O, et al: Iatrogenic biliary injury: 13,305 cholecystectomies experienced by a single surgical team over more than 13 years, Surg Endosc 22(4):1077­1086, 2008. Tocchi A, et al: the need for antibiotic prophylaxis in elective laparoscopic cholecystectomy: a prospective randomized study, Arch Surg 135(1):67­70, discussion 70, 2000. Toouli J, et al: Division of the sphincter of Oddi for treatment of dysfunction associated with recurrent pancreatitis, Br J Surg 83(9):1205­ 1210, 1996. Tsui C, et al: Minimally invasive surgery: national trends in adoption and future directions for hospital strategy, Surg Endosc 27(7):2253­ 2257, 2013. Varadarajulu S, et al: Determination of sphincter of Oddi dysfunction in patients with prior normal manometry, Gastrointest Endosc 58(3):341­344, 2003. Vecchio R, et al: Laparoscopic cholecystectomy: an analysis on 114,005 cases of United States series, Int Surg 83(3):215­219, 1998. Vezakis A, et al: Intraoperative cholangiography during laparoscopic cholecystectomy, Surg Endosc 14(12):1118­1122, 2000. Viceconte G, Micheletti A: Endoscopic manometry of the sphincter of Oddi: its usefulness for the diagnosis and treatment of benign papillary stenosis, Scand J Gastroenterol 30(8):797­803, 1995. Waage A, Nilsson M: Iatrogenic bile duct injury: a population-based study of 152 776 cholecystectomies in the Swedish Inpatient Registry, Arch Surg 141(12):1207­1213, 2006. Zehetner J, et al: Lost gallstones in laparoscopic cholecystectomy: all possible complications, Am J Surg 193(1):73­78, 2007. Hepatolithiasis is most prevalent in East Asia, is characterized by recurrent bouts of cholangitis, and unless properly treated, can lead to sepsis, biliary cirrhosis, and death. Although the incidence of primary hepatolithiasis has decreased due to urbanization of the endemic areas, secondary hepatolithiasis associated with past biliary surgery and hepatolithiasis associated with biliary malformation have increased with recent increases in hepatobiliary surgery and increased long-term survival. Treatment of hepatolithiasis can be broadly divided into partial hepatectomy and endoscopic treatment. Treatment must be tailored to each patient, depending on performance status and stone location. With liver resection, bile duct strictures can also be eliminated, so stone recurrence rates are generally lower. Hepatectomy can be performed when the disease is limited to one hemiliver with atrophy. Acquired factors, including changes in bile composition, biliary obstruction and stasis, and infection are thought to play a more essential role than congenital or genetic factors (Balasegaram, 1972). The higher incidence of hepatolithiasis in rural areas compared with urban areas also suggests roles for poor nutrition and environmental factors (Hamaloglu, 1992; Matsushiro et al, 1977). In Japan, as the process of urbanization advances, the chance of bacterial contamination decreases, which may also explain the decreasing incidence of bile pigment stones. Intrahepatic stones are classified by composition into calcium bilirubinate stones and cholesterol stones (see Chapter 8). Infection of the biliary tree has long been regarded as a cause of bile pigment stones. Maki and colleagues (Maki et al, 1962; Maki, 1966) found increased -glucuronidase activity in bile harboring bile pigment stones. It is suggested that increased activity of -glucuronidase caused by bacterial contamination may be an important factor for lithogenicity. Glucuronic acid­conjugated bilirubin, the major component of bile bilirubin, is water soluble. However, it converts to unconjugated bilirubin, which is less soluble when it is hydrolyzed by -glucuronidase, possibly derived from bacteria. It is thought that unconjugated bilirubin combines with a calcium ion in bile, then is deposited as bilirubin calcium. On the other hand, bile from patients with hepatolithisis contains significant amounts of hexosamines, hexoses (galactose and mannose), and sulfated glycoproteins, whereas the fractions obtained from normal bile do not contain these sulfated glycoproteins. Acid mucopolysaccharides, such as hexose, hexosamine and L-fructose, which are found in the gallstones, are presumed to provide a bridging mechanism in the coagulation of calcium carbonate particles (Matsushiro et al, 1968, 1977). Cholesterol in hepatic bile may result from relative cholesterol supersaturation due to increased cholesterol secretion from hepatocytes or due to decreased bile phospholipids and bile acids (Shoda et al, 1995). In Japan, the Ministry of Health, Labor, and Welfare organized a research group to evaluate the epidemiology and to improve outcomes. This hepatolithiasis research group has conducted nationwide surveys seven times in the past 40 years. Their studies revealed that the incidence of hepatolithiasis among all patients with gallstone disease decreased from 3% to 1. Although hepatolithiasis has largely been limited to Asia, with more common worldwide travel and increasing Asian immigration to 642 A. Transporter proteins in the bile canalicular membrane are involved in secretion and thus may also be a factor leading to changes in bile composition (Trauner et al, 1998). In addition, in biliary tract infection, pathogen-associated molecular patterns, such as bacterial lipopolysaccharide and lipoteichoic acid, bind to Toll-like receptors on bile duct epithelial cell membranes. The production of inflammatory cytokines from bile duct epithelium is also increased. These factors are associated with stone formation and chronic proliferative cholangitis. This disease entity includes recurrent pyogenic cholangitis (see Chapter 44), which is endemic in Southeast Asia, as first reported in 1930 by Digby and colleagues (1930) at Hong Kong University. Clonorchiasis (Clonorchis sinensis), ascariasis (Ascaris lumbricoides), and fasciolosis, (Fasciola spp. Fluke eggs in the feces or bile and peripheral blood eosinophilia are important diagnostic findings for this disease. The presence of hepatolithiasis in regions without endemic parasitic infection supports the concept that biliary parasites may not be regarded as a primary cause of hepatolithiasis. However, an etiologic role for these genetic factors remains uncertain (Furukawa et al, 1994). Secondary Hepatolithiasis Secondary hepatolithiasis associated with past biliary surgery and congential biliary malformation are examples where the etiology can be presumed (Kim et al, 1995). Intrahepatic stones are detected in 12% to 17% of adult patients with congenital choledochal cysts (Matsumoto et al, 2003; Morine et al, 2013). With recent increases in hepatobiliary surgery and increased long-term survival, secondary hepatolithiasis due to stenosis of bilioenteric or duct-to-duct biliary anastomoses has increased (Pitt et al, 1994; Schmidt et al, 2002). Special attention has focused on congenital choledochal cysts as a condition often associated with both intrahepatic bile duct strictures and biliary dilation. Congenital choledochal cysts are associated with intrahepatic stones (Fujii et al, 1997) as well as a high incidence of biliary tract carcinoma (10. Bile contamination associated with biliary strictures, anastomotic strictures, and hepaticojejununal (Rouxen-Y) anastomosis may be contributing factors (Kaneko et al, 2005), but much remains unknown about the mechanisms of onset. In addition to the increased potential of carcinogenesis due to long-term stimulation of biliary mucosa by pancreatic juice, bilioenteric anastomosis itself may accelerate carcinogenesis due to irritation by contaminated bile, even in benign conditions (Bettschart et al, 2002; Hakamada et al, 1997; Tocchi et al, 2001) (see Chapter 51). The risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts has been reported as 0. Therefore careful long-term surveillance is important after hepaticojejunostomy in congenital biliary cysts because it is suspected that the risk of cancer is doubled (Tsuyuguchi et al, 2014). Cholangiocarcinoma the development of cholangiocarcinoma in patients with hepatolithiasis is associated with poor long-term outcomes (see Chapter 51). The incidence of cholangiocarcinoma in patients with hepatolithiasis reported from Asian centers ranges from 2. In contrast, hepatolithiasis is uncommon in Western countries, with an incidence up to 2. Vetrone and colleagues (2006) found only one case with intramucosal adenocarcinoma of the extrahepatic bile duct out of 22 patients with hepatolithiasis who underwent surgical therapy. On the other hand, Tabrizian and colleagues (2012) reported a much higher incidence of concomitant cholangiocarcinoma of 23. Also, Al-Sukhni and colleagues (2008) reported that cholangiocarcinoma was identified in 5 of 42 (12%) patients during a 20-year study period. Guglielmi and colleagues (2014) prospectively collected a cohort of 161 patients with hepatolithiasis from five Italian tertiary hepatobiliary centers. Although the association of hepatolithiasis and cholangiocarcinoma is well recognized, the exact mechanism of carcinogenesis is still unclear. Persistent inflammation due to cholangitis causes repeated tissue damage and regeneration. Hyperplastic epithelial cells often showed a papillomatous or adenomatous pattern, which was frequently associated with the presence of stones (Koga et al, 1985). Ohta and colleagues (1991) reported that various degrees of hyperplastic biliary epithelium were associated with chronic proliferative cholangitis and existed around impacted stones. Mucosal dysplasia with expression of mucin core proteins and cytokeratins may be a precursor to cholangiocarcinoma (Zen Y, et al, 2006). There has been no clear symptom or clinical presentation associated with the presence cholangiocarcinoma in patients with hepatolithiasis. Therefore the possibility of coexisting cholangiocarcinoma should be considered in all cases, but especially so with unusual presentations, such as weight loss, anemia, or intractable pain (Sheen-Chen, 1991). Chijiiwa and colleagues (1995) reported that, among 85 patients with hepatolithiasis, 6 (7%) died of cholangiocarcinoma during a mean follow-up period of 6 years. Cheon et al (2009) also reported that the rate of late development of cholangiocarcinoma in patients with intrahepatic stones during follow-up was 4. The mean interval from the initial treatment to the development of cholangiocarcinoma was 10. Half of the patients developed cholangiocarcinomas at a site different from the initial site of hepatolithiasis. According to a Japanese survey, age older than 65 years and stone removal as the only initial treatment were significant risk factors for the subsequent development of cholangiocarcinoma (Suzuki Y et al. Further subgroup analysis revealed that age older than 65 years and the presence of biliary stricture were significant risk factors for the development of cholangiocarcinoma in patients with a history of bilioenteric anatomosis. In hepatolithiasis patients without a history of a bilioenteric anatomosis, left lobe location and stone recurrence were significant risk factors for the development of cholangiocarcinoma. Treatment with partial hepatectomy was a significant associated with reduced risk of cholangiocarcinoma. A recent survey revealed that a history of choledochoenterostomy and liver atrophy were significant predictive factors for the development of cholangiocarcinoma (Suzuki et al, 2012). Cholangiocarcinoma is likely to be found in atrophic liver with obliterated portal flow (Kubo et al, 1995). Thus hepatectomy of the atrophic liver with intrahepatic stones and biliary strictures may reduce the risk of cholangiocarcinoma (Uenishi et al, 2009). Severe cholangitis is sometimes concomitant with liver abscess and bacteremic shock. Gallstones and Gallbladder Chapter 39 Intrahepatic stones 645 disseminated intravascular cholangiopathy. According to a Japanese survey, 20% of patients with hepatolithiasis have no symptoms (Nimura et al, 2000). During long-term follow-up of patients with asymptomatic hepatolithiasis, 14 of 122 patients (11. In difficult-to-treat cases, when stones cannot be completely removed or bile duct strictures are not eliminated, hepatolithiasis is likely to recur. Symptoms occur in patients with biliary cirrhosis due to chronic recurrent cholangitis, who then often progress to liver failure. Patients in whom cholangiocarcinoma develops during follow-up often present with an abdominal mass, bloating due to ascites, and body weight loss. The diagnosis of acute cholangitis is usually made, or at least suspected, on the basis of the history and physical examination. However, only 50% to 70% of the patients exhibit all the three features at acute presentation. Blood test findings commonly show an elevated white blood cell count, elevated levels of hepatobiliary enzymes, and hyperbilirubinemia.

Benjaminov F symptoms 7 generic thyroxine 200 mcg fast delivery, et al: Effects of age and cholecystectomy on common bile duct diameter as measured by endoscopic ultrasonography medicine 81 generic 25 mcg thyroxine otc, Surg Endosc 27(1):303­307 treatment plan thyroxine 50 mcg purchase without a prescription, 2013 schedule 8 medicines cheap thyroxine 100 mcg without prescription. Delgado-Aros S symptoms zithromax thyroxine 125 mcg low cost, et al: Systematic review and meta-analysis: does gallbladder ejection fraction on cholecystokinin cholescintigraphy predict outcome after cholecystectomy in suspected functional biliary pain Douros A, et al: Drug-induced acute pancreatitis: results from the hospital-based Berlin case-control surveillance study of 102 cases, Aliment Pharmacol Ther 38(7):825­834, 2013. Halldestam I, et al: Incidence of and potential risk factors for gallstone disease in a general population sample, Br J Surg 96(11):1315­1322, 2009. Jorgensen T: Abdominal symptoms and gallstone disease-an epidemiological investigation, Hepatology 9(6):856­860, 1989. Jorgensen T, et al: Persisting pain after cholecystectomy-a prospective investigation, Scand J Gastroenterol 26(1):124­128, 1991. Kahaleh M, et al: Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia, Am J Gastroenterol 99(12):2335­ 2339, 2004. Kirk G, et al: Preoperative symptoms of irritable bowel syndrome predict poor outcome after laparoscopic cholecystectomy, Surg Endosc 25(10):3379­3384, 2011. Ksidzyna D: Drug-induced acute pancreatitis related to medications commonly used in gastroenterology, Eur J Intern Med 22(1):20­25, 2011. Kuy S, et al: Age matters: a study of clinical and economic outcomes following cholecystectomy in elderly Americans, Am J Surg 201(6): 789­796, 2011. Lien H-H, et al: Changes in quality-of-life following laparoscopic cholecystectomy in adult patients with cholelithiasis, J Gastrointest Surg 14(1):126­130, 2010. Lill S, et al: Elective laparoscopic cholecystectomy for symptomatic uncomplicated gallstone disease: do the symptoms disappear Nagem R, Lazaro-da-Silva A: Cholecystolithiasis after gastric bypass: a clinical, biochemical, and ultrasonographic 3-year follow-up study, Obes Surg 22(10):1594­1599, 2012. Rastogi A, et al: Controversies concerning pathophysiology and management of acalculous biliary-type abdominal pain, Dig Dis Sci 50(8):1391­1401, 2005. Schmidt M, et al: A 24 year controlled follow-up of patients with silent gallstones showed no long-term adverse events leading to cholecystectomy, Scand J Gastro 46(7­8):949­954, 2011. Talukdar R, et al: Clinical utility of the Revised Atlanta Classification of acute pancreatitis in a prospective cohort: have all loose ends been tied Theocharidou E, et al: the Royal Free Hospital score: a calibrated prognostic model for patients with cirrhosis admitted to intensive care unit. Toouli J: Sphincter of Oddi: function, dysfunction, and its management, J Gastroenterol Hepatol 24(Suppl 3):S57­S62, 2009. Videhult P, et al: Are liver function tests, pancreatitis and cholecystitis predictors of common bile duct stones Warschkow R, et al: Concomitant cholecystectomy during laparoscopic Roux-en-Y gastric bypass in obese patients is not justified: a metaanalysis, Obes Surg 23(3):397­407, 2013. In this article, we will review a few emerging techniques in diagnostic imaging with relevance to hepatopancreaticobiliary tumors. New dose modulation techniques have also reduced the radiation dose exposure for patients. X-rays represent electromagnetic waves (photons) of very high energy and very short wavelengths that can pass through most objects, allowing us to "see" through the body. The degree of x-ray attenuation (or interaction) by different elements in our body is related to the number of electrons present in each element. The higher the atomic number of an element, the greater the number of electrons present that can potentially interact with x-rays. In simplistic terms, x-rays will be more frequently scattered or absorbed by the photoelectric effect when they travel through bones, which are high in calcium (Ca20), than when traveling through other soft tissues made of hydrogen (H1), carbon (C6), nitrogen (N7), and oxygen (O8), which are lower in atomic number. The first is in changing the image contrast between iodine and other elements, for example, by increasing the conspicuity of tumors that enhance using iodinated contrast. At lower x-ray energy, the attenuation of iodinated contrast is magnified compared with soft tissue, which can alter the conspicuity of subtle enhancing lesions. Quantifying iodine can improve our ability to measure treatment response, for example, in therapies in which tumor vascularization (and enhancement) is affected and changes in tumor attenuation are informative (Uhrig et al, 2013). Fat quantification, in patients at risk for hepatic steatosis, for example, is also another potential application of this technique (Hur et al, 2014). Tumor response to chemotherapy has traditionally been assessed by measurements of tumor size, such as through guidelines from the Response Assessment Criteria in Solid Tumors rules. With cytotoxic therapies, reduction in size of tumors is expected with a good response to therapy. However, as new targeted therapies may inhibit vascularization or act as cytostatic agents, traditional response criteria based on tumor shrinkage may underestimate therapeutic effectiveness. For example, parameters can be measured at baseline and compared on follow-up posttreatment scans. Efforts are ongoing to reduce the variability and improve standardization of imaging parameters by the Quantitative Imaging Biomarker Alliance, formed by the Radiological Society of North America. Thus it is often referred to as a dual-function contrast agent, allowing the evaluation of both tumor and liver parenchymal enhancement in the same study (Sirlin et al, 2014). Thus an emerging body of research has focused on the diagnostic performance of radiologists. One of the criticisms of published retrospective radiology studies that report on the accuracy of imaging modalities for different clinical questions has been the use of consensus interpretation among expert readers (Bankier et al, 2010). Individual interpretation, rather than consensus interpretation, is the norm in routine clinical practice. A method to reduce the potential variability among diagnostic radiologists is the establishment of diagnostic imaging criteria. The possibility that different radiologists may interpret "washout appearance" with some variability was well known (Liu et al, 2013). Thus despite efforts at standardization with the development of diagnostic guidelines, variability in the performance of diagnostic radiologists can remain substantial in specific clinical scenarios and a source of uncertainty for clinical management. These studies are important acknowledgements of the variability inherent in diagnostic imaging that extend beyond the imaging techniques themselves. One method to reduce this variability will come from the use of computer software to aid in the interpretation of medical images and the quantification of imaging features. Radiomics is a growing field of study, with a focus on improving image analysis through the extraction of large amounts of advanced quantitative features of medical images, through automatic or semiautomatic software that can provide more and better information than a physician (Lambin et al, 2012). The features that are reproducible and most informative are then analyzed for their relationship with treatment outcomes or gene expression. An underlying hypothesis for radiomics is that genomic and proteomics patterns of malignancies can be expressed in macroscopic image-based features. Until recently, the heterogeneity of tumors on imaging was commonly observed but seldom assessed qualitatively by diagnostic radiologists or quantitatively by computer software. Tumor heterogeneity observed on imaging has the potential to reflect molecular and cellular dynamics that may be specific to individual patients and may be predictive of response to targeted therapies that are increasingly in use (Gatenby et al, 2013). Gatenby and colleagues propose that heterogeneity in tumor enhancement is based on perfusion deficits, which can generate significant microenvironmental selection pressures, and that adaptive response to heterogeneity can lead to the emergence of genetic variations within tumors. Quantifying tumor heterogeneity on imaging, to uncover differences in genetic background of individual tumors, can thus form the basis for patient-specific therapies in cancer treatment. Multiple studies have begun to uncover the potential of texture analysis for outcome analyses in multiple tumors. Texture analysis of an image can be defined as the measurement of variations in pixel intensity levels. The potential of radiomics to capture tumor heterogeneity in lung and head and neck cancers, and their association with gene-expression patterns has been described (Aerts et al, 2014). To date, limited radiogenomics studies have been performed in hepatopancreaticobiliary tumors (Rao et al, 2014; Segal et al, 2007). During the development of liver cirrhosis, the liver acquires a characteristic nodular contour, and the liver parenchyma is also altered in appearance with an increasingly reticular enhancement pattern. Texture analysis of liver parenchyma also has the potential to predict liver failure after major hepatic resection (Simpson et al, 2014). Thus quantitative image analyses can be extended beyond radiomics for tumor prognostication, to the potential prediction of hepatic and pancreatic function. Novel imaging devices, contrast agents, and functional techniques continue to emerge and provide improvements in biologic insight for medical decision making. However, the variability inherent to imaging technique and diagnostic radiologists themselves can affect the diagnostic performance of an imaging study, and is increasingly the subject of investigation. This acknowledgement is leading to the emergence of standardization in radiologic reports and image acquisition parameters, as well as greater interest in the use of computer-based analyses and the development of radiomics. Bahl G, et al: Noninvasive classification of hepatic fibrosis based on texture parameters from double contrast-enhanced magnetic resonance images, J Magn Reson Imaging 36(5):1154­1161, 2012. American Association for the Study of Liver: Management of hepatocellular carcinoma: an update, Hepatology 53(3):1020­1022, 2011. Cui Y, et al: Apparent diffusion coefficient: potential imaging biomarker for prediction and early detection of response to chemotherapy in hepatic metastases, Radiology 248(3):894­900, 2008. Hylton N: Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker, J Clin Oncol 24(20):3293­3298, 2006. Lambin P, et al: Radiomics: extracting more information from medical images using advanced feature analysis, Eur J Cancer 48(4):441­446, 2012. Segal E, et al: Decoding global gene expression programs in liver cancer by noninvasive imaging, Nat Biotechnol 25(6):675­680, 2007. Ultrasound is considered safe at clinical, diagnostic levels, with no confirmed harmful biologic effects on the operator or patient. Despite these advantages, certain limitations influence the applicability of ultrasound. Ultrasound waves are unable to penetrate bone or air, which can obscure lesions and limit the field of view. The quality of ultrasound imaging and its interpretation are also operator dependent; ultrasound imaging and diagnosis is greatly influenced by skill and experience. Principles of Ultrasound Interpretation In diagnostic ultrasound applications, brief pulses of acoustic energy are emitted by the transducer, transmitted into the body, reflected from acoustic interfaces, and received by the transducer. The average velocity of sound in soft tissues is 1540 m/s, with reduced velocities in fat and increased velocities in bone. The ultrasound unit uses precise timing to interpret and process information included in the returning echoes, including frequency, amplitude, and phase information. Ultrasound units assume a uniform propagation velocity of sound to compute the depth of the interface reflecting the pulse and then to generate an imaging display. This pulse-echo principle allows inference of the position, nature, and motion of the interface from which the received echo originated. Lower-frequency transducers have poorer resolution with greater depth of penetration, and thus are used to image deeper structures such as abdominopelvic tissues. Higher-frequency transducers have better spatial resolution, but higher-frequency sound attenuates rapidly and has poorer tissue penetration. The depth of the target structure is a major determinant of the transducer frequency. Gray Scale Ultrasound Terminology and Artifacts Echogenicity of tissue refers to the reflection or transmission of ultrasound waves relative to surrounding tissues. Tissue harmonic imaging is a gray scale ultrasound setting that is useful in transabdominal ultrasound for depicting cystic lesions and lesions containing echogenic material such as air, calcification, or fat. Harmonic imaging also improves lesion visibility in patients with a higher body mass index (Choudhry et al, 2000). Acoustic enhancement is an artifact that occurs when there is increased through-transmission of sound waves in fluid-containing structures, making tissue behind the fluid appear artificially bright. This occurs because ultrasound units adjust for a certain attenuation of sound with depth of travel such that there is erroneous amplification of echoes deep to fluid-containing structures. Acoustic shadowing occurs when a structure attenuates sound more rapidly than surrounding tissues and casts a dark acoustic shadow beyond the object. This occurs with strong reflectors, such as calcifications, or strong attenuators, such as dense tumors. Reverberation artifact occurs when the ultrasound beam is repeatedly reflected back and forth between two parallel highly reflective surfaces, such as walls of a fluidfilled structure, producing artifactual echoes due to propagation assumption by the ultrasound processor. Reverberations may produce the false appearance of echoes within fluid or make a cystic structure appear solid. Comet tail artifact is a type of reverberation that occurs when two reflective interfaces are closely spaced, such as within a punctate crystal, producing posterior echoes that are parallel, evenly spaced echogenic bands with a triangular tapered shape. Twinkle artifact is a color Doppler artifact that helps to detect and verify crystals and calcifications, particularly if a calculus does not demonstrate acoustic shadowing. Twinkle artifact occurs posterior to strong reflectors and appears as turbulent color Doppler flow with a mix of red and blue pixels; however, spectral Doppler tracing demonstrates noise. Additional artifacts have been described and are outside the scope of this chapter; the reader is referred to specialized texts (Campbell et al, 2004; Feldman et al, 2009; Rubens et al, 2006). Doppler Ultrasound Doppler ultrasound is used to identify and evaluate blood flow in vessels based on the backscatter of blood cells. Echoes returning from moving targets change in frequency compared with the transmitted pulse. This change in frequency is proportional to the velocity of the reflector relative to the transducer and is defined by the Doppler effect. Transverse gray scale ultrasound image of the liver showstherighthepaticvein(hv)asananechoicfluid-containingstructure. Gallstones (curved arrow) layering in the gallbladder produceanacousticshadow(straight arrows). Color Doppler provides information about the direction of motion and differences in flow velocity. Echoes from red blood cells are displayed in colors designated for flow toward or away from the transducer.

Thyroxine 125 mcg overnight delivery. HIV seroconversion symptoms.

Accurate recording of alcohol intake must be made treatment norovirus purchase thyroxine 125 mcg without prescription, because ongoing heavy alcohol use impacts treatment for chronic liver or pancreatic diseases treatment urticaria effective thyroxine 200 mcg. Occasionally medications held for dialysis order thyroxine 200 mcg with visa, patients attend the clinic smelling of alcohol in their breath treatment episode data set order 25 mcg thyroxine free shipping, yet deny ongoing alcohol use medications listed alphabetically purchase line thyroxine, and this should be noted. A request for a blood alcohol level could be made, provided the patient consents to it. A past medical history should be obtained to include any major illnesses and any abdominal surgery. A record of comorbidities and exercise tolerance should be made, as this will guide the surgeon in assessing fitness for future intervention if required (see later). This should be followed by a family history, drug history, social circumstances, employment, and travel. Abdominal pain is often a presenting symptom, and a detailed enquiry of the site, severity, radiation, and rapidity of onset will allow some clues to a differential diagnosis. Suddenonset severe upper abdominal pain radiating to the back is characteristic of acute pancreatitis (see Chapters 55 and 56), whereas right-side upper quadrant pain may indicate acute inflammation of the gallbladder (see Chapter 33). Any associated nausea and vomiting should be recorded along with a history of jaundice (sclerae), color of urine and stools, and any associated itching. A history of abdominal distension may point to an ileus in acute presentations and to ascites or bowel obstruction in chronic liver disease or a malignant process. Steatorrhea is characterized by the passage of foul-smelling stools, which float on water and may indicate pancreatic exocrine insufficiency (see Chapters 57, 58, and 62). Full exposure of the abdomen in good light is important for an adequate inspection. Particular attention should be paid to any scars from previous abdominal surgery, abdominal distension, and areas of discoloration. Palpation of the abdomen should begin with a general light palpation, looking for obvious masses or areas of tenderness. The healthy liver is usually impalpable; however, in very thin individuals, the anterior edge may be palpable. A lobe may undergo hypertrophy and become palpable, and this may occur in the presence of hemiliver atrophy or after liver resection. Reduction in liver size also is important because this may occur in cirrhosis and certain types of hepatitis. Rotation of the patient 45 degrees to the right may aid palpation, because the spleen then falls onto the examining right hand. During this maneuver, the left hand should support the rib cage and relax the skin and abdominal musculature by drawing these down to the right. Percussion may be useful, and if ascites is present, the spleen may be ballotable. If the spleen is sufficiently enlarged, the notch on its anterior border may become palpable. The liver is examined using a combination of palpation and percussion from above and below to delineate its borders. Dullness to percussion of the upper border extends as far as the fifth intercostal space. Auscultation is also important because a venous hum may be heard with portal hypertension, and a bruit may be heard in association with hepatocellular carcinomas. Portal Hypertension Portal hypertension is due to either intrahepatic or extrahepatic portal venous obstruction (see Chapters 76 and 79). The more common clinical site of portosystemic anastomosis is at the gastroesophageal junction, leading to esophageal varices; any evidence of upper gastrointestinal blood loss, whether hematemesis or melena, should be investigated with urgent endoscopy. Extrahepatic portal hypertension is usually due to portal vein thrombosis, and as such it is important to identify any history of neonatal infection around the umbilicus, major intraabdominal sepsis or pancreatitis, pancreatic cancer, or a blood disorder that might lead to hypercoagulability. These patients almost invariably have splenomegaly, often associated with pancytopenia. A palpable spleen in the upper left abdomen associated with portal hypertension may be found in the event of splenic occlusion caused by tumor or chronic pancreatitis. Acute alcoholic hepatitis usually occurs after a bout of drinking and may be associated with liver tenderness, jaundice, pyrexia, and leukocytosis. These patients often are seen recurrently with epigastric pain, which can be severe. They will usually admit to a bout of heavy drinking, which precipitates their symptoms. Advanced alcoholic liver disease may be associated with other manifestations of hepatic impairment. Decompensated liver failure results in the development of encephalopathy, jaundice, ascites, fatigue, polydipsia, easy bruising, mood fluctuation and often is marked by nutritional depletion. Primary biliary cirrhosis, or chronic nonsuppurative destructive cholangitis, usually affects middle-aged women. Asymptomatic individuals may be diagnosed during routine examination, where they are found to have hepatomegaly, elevated autoantibodies, or elevated plasma alkaline phosphatase. The earliest symptom is usually unrelenting pruritus, even before clinical jaundice is apparent, but later the patient may experience overt jaundice; hepatosplenomegaly; xanthelasma, especially in the palms and around the eyes; vitiligo; and arthritis. Primary biliary cirrhosis is often found in association with connective tissue disease (see Chapter 112). Primary Sclerosing Cholangitis Ulcerative colitis and Crohn disease are associated with hepatobiliary disorders, especially primary sclerosing cholangitis (see Chapter 41). It is important to include a detailed gastrointestinal systems review and investigations in any patient with unexplained liver dysfunction. Symptoms are usually nonspecific, with itching, right upper quadrant discomfort, fatigue, and weight loss. Parenchymal liver disease is graded in severity with the Child-Pugh score (Table 13. Budd-Chiari Syndrome Budd-Chiari syndrome is characterized by venous outflow obstruction to the liver, which could be intrahepatic or extrahepatic (see Chapter 88). Acute venous obstruction is usually secondary to another pathologic process and presents with abdominal pain, vomiting, hepatomegaly, ascites, and jaundice, which may be mild. Chronic venous obstruction of the liver usually presents with gross ascites and hepatomegaly. If the inferior vena cava is blocked with tumor or thrombus, gross edema of the legs and superficial venous distension of the abdominal veins is apparent. Alcoholic Liver Disease the symptoms and signs of alcoholic liver disease may be related directly to alcoholism or to secondary hepatocellular dysfunction. Patients commonly experience repeated falls while inebriated and may have signs of trauma and bruising. Multiple "old" rib fractures are common findings on chest radiographs and are related to such behavior. This can occur as a result of paracetamol (acetaminophen) toxicity, usually caused by overdosage, from a massive viral infection or, rarely, by fulminant autoimmune hepatitis. Symptoms include itching, jaundice, right upper quadrant pain or discomfort (which may mimic acute cholecystitis), and nonspecific flulike symptoms. Diagnosis is established by the history, massively elevated serum aminotransfererases, and rapidly rising prothrombin time. Acute-on-chronic liver failure occurs frequently and is characterized by acute decompensation of liver cirrhosis, multiorgan failure and a high mortality. This is now considered a clinical entity, and scoring systems for its prognostication have recently been developed (Karvellas et al, 2014; Theocharidou et al, 2014) (see Chapters 79, 80, and 114). Hemochromatosis Hematochromatosis is an iron overload state in which the liver is usually affected. Excess iron deposition leads to fibrosis and cirrhosis with an increased risk of developing hepatocellular carcinoma. Clinically, hemochromatosis usually presents between the ages of 40 and 60 years and predominantly in men. Symptoms are usually nonspecific, with lethargy, increased pigmentation, loss of body hair, loss of libido, arthralgia, and diabetes, usually due to the involvement of the pancreas. Clinical examination may show hepatomegaly and hyperpigmentation in the axillae, groins, and genitalia as well as testicular atrophy. Diagnosis is made by hematologic tests, including serum iron, serum ferritin, and serum transferrin; liver damage can be assessed with a liver biopsy. Acute abdominal pain is usually due to infection or bleeding into a cyst (see Chapters 75 and 90B). Associated autoimmune diseases can occur in as many as 30% of patients and must be excluded. These include Sjögren syndrome, autoimmune thyroiditis, hemolysis, rheumatoid arthritis, ulcerative colitis, and idiopathic thrombocytopenic purpura. Liver Masses Patients with large liver masses may be seen initially with right upper quadrant discomfort or a palpable mass in the upper abdomen. More often, liver masses are discovered during imaging as part of the investigation of jaundice, nonspecific abdominal symptoms, or follow-up of malignancy. If the liver mass is discovered incidentally, a full clinical history should be obtained, with particular attention to gastrointestinal and respiratory symptoms. Details and duration of oral contraceptive and anabolic steroid use should be recorded, and the possibility of viral hepatitis should be considered. A thorough abdominal examination should be performed, especially for abnormal masses and ascites, and a digital rectal examination is mandatory at the initial assessment. Signs of jaundice, liver insufficiency, and development of collateral circulation should be sought. A comprehensive hematologic and biochemical screening (Box 13-4) should include an assessment of coagulation factors and of common tumor markers (-fetoprotein, carcinoembryonic antigen, cancer Liver Disease in Pregnancy Acute fatty liver of pregnancy may present to the surgeon with liver subcapsular hematoma or rupture with massive intraabdominal bleeding. Biopsy of liver masses should not be performed until potentially curable conditions have been ruled out due to the risk of extrahepatic seeding. The two most important of these are metastatic colorectal cancer and primary hepatocellular carcinoma (see Chapters 89 to 95). If the gallbladder is palpable in the presence of obstructive jaundice, this suggests malignant obstruction of the biliary tree (Couvoisier law), which is commonly due to carcinoma in the head of the pancreas (see Chapter 62). Failure to palpate the gallbladder does not exclude malignant disease, however, and a nonpalpable gallbladder is the rule in malignant obstruction at the hilus of the liver. A gallbladder that is intermittently palpable may suggest the presence of a periampullary carcinoma (Kennedy & Blumgart, 1971). Gallbladder distension and signs of sepsis in the presence of gallstones may indicate empyema of the gallbladder. In such instances, initial treatment consists of percutaneous aspiration and drainage, with a cholecystectomy delayed for some time. It arises as the result of acute inflammation of a distended, obstructed, and usually infected gallbladder. Patients may be more comfortable lying still because of the associated localized peritonitis, and coughing or sneezing may exacerbate the pain. An infected, obstructed gallbladder sometimes ruptures and causes generalized peritonitis or a liver abscess. It is important to examine patients with acute cholecystitis regularly, and if the pain and tenderness do not settle rapidly with antibiotic therapy, percutaneous drainage of the gallbladder (cholecystostomy) (see Chapter 30,) or an emergency cholecystectomy (see Chapter 35) may be required. The Tokyo Guidelines for the diagnosis of acute cholangitis and acute cholecystitis were updated in 2013 (Boxes 13. Biliary Colic Biliary colic, which is a clinical entity distinct from acute cholecystitis, usually has a crescendo-decrescendo pattern, with the pain slowly building up to a peak during a few hours; this peak is often associated with vomiting, and the pain then gradually subsides during the ensuing few hours. Often the pain radiates to the back (Berhane et al, 2006), and this pattern of gallbladder pain is thought to arise from gallbladder nociceptors, in response to a rise in intracholecystic pressure caused by strong contraction of the gallbladder against an obstructed neck. In acute hepatitis, marked systematic inflammatory response is observedinfrequently. Cholelithiasis Symptomatic cholelithiasis is the commonest indication for cholecystectomy, and asymptomatic gallstones do not need intervention (Schmidt et al, 2011) (see Chapter 32). Unfortunately, the symptomatology of gallbladder stone disease has been hard to define despite research spanning decades (Johnson & Jenkins, 1975). A large epidemiologic investigation in Denmark into the relationship between abdominal symptoms and gallstones concluded that the predictive values of various abdominal symptoms for gallstones were very low. In patients with gallstones, the prevalence of right upper quadrant abdominal pain was similar to patients without gallstones but was higher in patients who had previously undergone cholecystectomy (Jorgensen, 1989; Jorgensen et al, 1991). The larger Multicenter Italian Study on Cholelithiasis showed that, in an Italian population, the presence of epigastric or right upper quadrant pain radiating to the right shoulder, forcing the patient to rest, and intolerance to fried or fatty food were good predictors of gallstones (Corazziari et al, 2008). A recent Swedish study that followed up 503 patients without gallstones for 5 years reported that the incidence of gallstone formation was 1. A retrospective analysis of patients referred for ultrasonography based on their symptoms showed that approximately half of these patients had gallstones or gallbladder pathology (Warwick et al, 2014). Studies examining the relief of symptoms after cholecystectomy suggest that a significant number of patients (as many as 40%) undergoing cholecystectomy will not experience relief of symptoms, and this symptomatic outcome was maintained at 10-year follow-up (Lamberts et al, 2014). A study comparing the symptomatic outcomes after cholecystectomy for functioning and nonfunctioning gallbladders showed no difference in outcome (Larsen et al, 2007). A questionnaire-based study of symptom relief in Finnish patients suggests that patients with severe preoperative symptoms are more likely to obtain relief of symptoms than those with mild symptoms (Lill et al, 2014). An important study outlined the variation in perceptions of what was considered a valid indication for cholecystectomy (Scott & Black, 1991). These authors showed the case histories of 252 patients to two panels, one comprising surgeons and the other a mixed panel of doctors. The mixed panel considered 41% of the operations appropriate for the indications and 30% inappropriate, but the surgeons considered 52% appropriate and 2% inappropriate but could not agree on the other 46%. A Korean study suggests that laparoscopic cholecystectomy led to an improvement in colonic and dyspeptic symptoms (Kim et al, 2014) but does not alter patterns of gastric emptying in patients (Bagaria et al, 2013). These attacks of pain can be widely variable in their occurrence, and some patients may have an interval of many years between attacks; others may have almost constant discomfort. Some patients report that the pain is triggered by certain foods, usually fatty foods, and some patients are afraid of eating for fear of triggering an attack of pain (sitophobia).

Gallstones and Gallbladder Chapter 36C Stones in the bile duct: endoscopic and percutaneous approaches 622 medications for rheumatoid arthritis discount thyroxine 200 mcg buy on-line. Das A schedule 8 medicines cheap 25 mcg thyroxine, et al: Treatment of biliary calculi using holmium:yttrium aluminium garnet laser medications given for uti 125 mcg thyroxine with visa, Gastrointest Endosc 48:207­209 symptoms cervical cancer thyroxine 100 mcg with visa, 1998 symptoms of a stranger buy thyroxine discount. Deviere J, et al: Successful management of benign biliary strictures with fully covered self-expanding metal stents, Gastroenterology 147:385­ 395, 2014. Diaz D, et al: Methyl tert-butyl ether in the endoscopic treatment of common bile duct radiolucent stones in elderly patients with nasobiliary tube, Dig Dis Sci 37:97­100, 1992. DiSario J, et al: Biliary and pancreatic lithotripsy devices, Gastrointest Endosc 65:750­756, 2007. Ersoz G, et al: Biliary sphincterotomy plus dilation with a large balloon for bile duct stones that are difficult to extract, Gastrointest Endosc 57:156­159, 2003. Escourrou J, et al: Early and late complications after endoscopic sphincterotomy for biliary lithiasis, with and without the gallbladder "in situ. The German Study Group on Acute Biliary Pancreatitis, N Engl J Med 336:237­242, 1997. Garcia-Cano J, et al: Fully covered self-expanding metal stents in the management of difficult common bile duct stones, Rev Esp Enferm Dig 105:7­12, 2013. Akcakaya A, et al: Mechanical lithotripsy and/or stenting in management of difficult common bile duct stones, Hepatobiliary Pancreat Dis Int 8:524­528, 2009. Arya N, et al: Electrohydraulic lithotripsy in 111 patients: a safe and effective therapy for difficult bile duct stones, Am J Gastroenterol 99:2330­2334, 2004. Bhandari S, et al: Usefulness of single-operator cholangioscope-guided laser lithotripsy in patients with Mirizzi syndrome and cystic duct stones: experience at a tertiary care center, Gastrointest Endosc 2016; Jan 5 [Epub ahead of print]. Boerma D, et al: Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile duct stones: a randomized trial, Lancet 360:761­765, 2002. Burdick J, et al: Holmium laser for treatment of left hepatic duct stone, Gastrointest Endosc 48:523­526, 1998. Cerefice M, et al: Complex biliary stones: treatment with removal selfexpandable metal stents: a new approach (with videos), Gastrointest Endosc 74:520­526, 2011. Classen M, Demling L: Endoscopische Sphinkterotomie der Papilla Vater, Dtsch Med Wochenschr 99:496­497, 1974. Grimm H, Soehendra N: Unterspritzung zur Behandlung der Papillotomie-Blutung, Dtsch Med Wochenschr 108:1512­1514, 1983. Hirano T, et al: A possible mechanism for gallstone pancreatitis: repeated short-term pancreaticobiliary duct obstruction with exocrine stimulation in rats, Proc Soc Exp Biol Med 202:246­252, 1993. Hochberger J, et al: Management of difficult common bile duct stones, Gastrointest Endosc Clin N Am 13:623­634, 2003. Ikeda S, et al: Endoscopic sphincterotomy: long-term results in 408 patients with complete follow-up, Endoscopy 20:13­17, 1988. Inamdar S, et al: Pregnancy is a risk factor for pancreatitis after endoscopic retrograde cholangiopancreatography in a national cohort study, Clin Gastroenterol Hepatol 14:107­114, 2016. Iwashita T, et al: Endoscopic ultrasound-guided rendezvous for biliary access after failed cannulation, Endoscopy 44:60­65, 2012. Katsinelos P, et al: the effect of indwelling endoprosthesis on stone size or fragmentation after long-term treatment with biliary stenting for large stones, Surg Endosc 17:1552­1555, 2003. Kawai K, et al: Endoscopic sphincterotomy of the ampulla of Vater, Gastrointest Endosc 20:148­151, 1974. Kiil J, et al: Large bile duct stones treated by endoscopic biliary drainage, Surgery 105:51­56, 1989. Kim U, Bosner B: Timing of surgery for acute gallstone pancreatitis, Am J Surg 156:393­396, 1988. Leese T, et al: Successes, failures, early complications and their management following endoscopic sphincterotomy: results in 394 consecutive patients from a single centre, Br J Surg 72:215­219, 1985. Madhoun M, et al: Endoscopic papillary large balloon dilation reduces the need for mechanical lithotripsy in patients with large bile duct stones: a systematic review and meta-analysis, Diagn Ther Endosc 2014:309618, 2014. Mador B, et al: Early versus delayed cholecystectomy following endoscopic sphincterotomy for mild biliary pancreatitis, Surg Endosc 28: 3337­3342, 2014. Maleux G, et al: Embolization of post-biliary sphincterotomy bleeding refractory to medical and endoscopy therapy: technical results, clinical efficacy and predictors of outcome, Eur Radiol 24:2779­2786, 2014. Mavrogiannis C, et al: Needle-knife fistulotomy versus needle-knife precut papillotomy for the treatment of common bile duct stones, Gastrointest Endosc 50:334­339, 1999. Maydeo A, et al: Single operator cholanioscopy-guided laser lithostripsy in patients with difficult biliary and pancreatic ductal stones, Gastrointest Endosc 74:1308­1314, 2011. Murphy P, et al: Implementation of an acute care surgery service facilitates modern clinical practice guidelines for gallstone pancreatitis, J Am Coll Surg 221:975­981, 2015. Nakajima M, et al: Five years experience of endoscopic sphincterotomy in Japan: a collective study from 25 centers, Endoscopy 2:138­141, 1979. Nordback I: Management of unextractable bile duct stones by endoscopic stenting, Ann Chir Gynaecol 78:290­292, 1989. Nowak A, et al: Final results of the prospective, randomized, controlled study on endoscopic sphincterotomy versus conventional management in acute biliary pancreatitis, Gastroenterology 108:A380, 1995. Picus D: Intracorporeal biliary lithotripsy, Radiol Clin North Am 28:1241­1249, 1990. Ponchon T, et al: Extracorporeal lithotripsy of bile duct stones using ultrasonography for stone localization, Gastroenterology 98:726­732, 1990. Rhodes M, et al: Laparoscopic exploration of the common bile duct: lessons learned from 129 consecutive cases, Br J Surg 82:666­668, 1995. Rhodes M, et al: Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones, Lancet 351:159­161, 1998. Rosch W, et al: Long-term follow-up after endoscopic sphincterotomy, Endoscopy 13:152­153, 1981. Sackman M, et al: Extracorporeal shock wave lithotripsy for clearance of bile duct stones resistant to endoscopic extraction, Gastrointest Endosc 53:27­32, 2001. Safrany L: Endoscopic treatment of biliary tract diseases, Lancet 2:983­ 985, 1978. Sauer B, et al: Safety and efficacy of laser lithotripsy for complicated biliary stones using direct choledochoscopy, Dig Dis Sci 58:253­256, 2013. Sauerbruch T, Stern M: Fragmentation of bile duct stones by extracorporeal shock waves: a new approach to biliary calculi after failure of routine endoscopic measures, Gastroenterology 96:146­152, 1989. Schumacher B, et al: Endoscopic treatment of symptomatic choledocholithiasis, Hepatogastroenterology 45:672­676, 1998. Seifert E, et al: Langzeitresultate nach endoskopischer Sphinkterotomie: follow-up-Studie aus 25 Zentren in der Bundesrepublik, Dtsch Med Wochenschr 107:610­614, 1982. Sethi S, et al: Prospective assessment of consensus criteria for evaluation of patients with suspected choledocholithiasis, Dig Endosc 28:75­82, 2016. Sherman S, et al: Complications of endoscopic sphincterotomy: a prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts, Gastroenterology 101:1068­1075, 1991. Siegel J, et al: Endoscopic electrohydraulic lithotripsy, Gastrointest Endosc 36:134­136, 1990. Tarantino I, et al: Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on safety, Endoscopy 44:923­927, 2012. Tenner S, et al: American College of Gastroenterology guideline: management of acute pancreatitis, Am J Gastroenterol 108:1400­1415, 2013. Tomizawa Y, et al: Combined Interventional interventional radiology followed by endoscopic therapy as a single procedure of patients with failed initial endoscopic biliary access, Dig Dis Sci 59:451­458, 2014. Tse F, et al: the elective evaluation of patients with suspected choledocholithiasis undergoing laparoscopic cholecystectomy, Gastrointest Endosc 60:437­438, 2004. Vaira D, et al: Endoscopic sphincterotomy in 1000 consecutive patients, Lancet 2:431­434, 1989. Ten to 20 percent of the Western population has gallstones, and the majority of patients with gallstones, about 65% to 80%, are asymptomatic (Sakorafas et al, 2007) (see Chapter 32). Studies of the natural history of silent gallstones have shown that symptoms develop in 1% to 2% of patients per year. Among patients with asymptomatic gallstones, about 10% develop symptoms in 5 years, and about 20% develop symptoms by 20 years. Therefore the majority of patients with asymptomatic gallstones can be observed, and surgical intervention (laparoscopic cholecystectomy) should be offered only when symptoms develop. There are certain groups for which prophylactic cholecystectomy has previously been recommended for asymptomatic gallstones. These populations include solid-organ transplant patients; diabetics; patients with chronic liver disease, sickle cell anemia or other chronic hemolytic anemias; patients undergoing bariatric or other gastrointestinal operations; and those with a potentially increased risk of gallbladder carcinoma (Table 37. Prophylactic cholecystectomy for asymptomatic cholelithiasis was previously recommended for patients with diabetes mellitus. Studies in the late 1960s reported a higher mortality following emergency cholecystectomy in diabetic patients; however, subsequent meta-analysis revealed that diabetes was not an independent variable. Rather, associated risk factors such as cardiovascular, peripheral vascular, cerebrovascular, or prerenal azotemia were associated with more severe acute cholecystitis (Hickman et al, 1988; Stewart et al, 1989). More recent series have shown similar complication rates for acute cholecystectomy among diabetic and nondiabetic patients. The incidence of gallstones is twice as high in patients with chronic liver disease. Operative morbidity and mortality rates for patients with chronic liver disease are also significantly higher. Although laparoscopic cholecystectomy has been shown to be safe in well-selected Child-Pugh class A and B cirrhotic patients, it is contraindicated in all but emergent settings in Child-Pugh class C patients due to high complication rates (Curro et al, 2005) (see Chapter 77). Owing to the association between morbid obesity and cholelithiasis, a high proportion of patients undergoing bariatric surgery have gallbladder pathology. Patients undergoing bariatric surgery have a higher incidence of cholelithiasis, related both to obesity and rapid weight loss. Some surgeons use bile salt medications during periods of rapid weight change to help prevent cholesterol gallstone formation; however, more recent studies have shown that this approach is not cost-effective (BenarrochGampel et al, 2012). Several factors must be considered for potential solid-organ transplant patients with asymptomatic cholelithiasis. In these patients, cholelithiasis is common, immunosuppression may increase infectious morbidity, and morbidity and mortality may be increased with emergency surgery. This problem was examined with a recent decision analysis, using probabilities and outcomes derived from a pooled analysis of published studies (Kao et al, 2005). For pancreas and kidney transplant patients with asymptomatic cholelithiasis, however, expectant management was recommended, an approach that is widely agreed upon in the literature (Melvin et al, 1998). Kao and colleagues (2005) recommended prophylactic posttransplantation cholecystectomy for cardiac transplant recipients with asymptomatic cholelithiasis, an approach advocated by other studies as well because of the increased morbidity and mortality that has been demonstrated with subsequent urgent or emergent cholecystectomy compared with the general populace (Kilic et al, 2013). This remains an area of debate, however, as other studies have demonstrated that expectant management of asymptomatic gallstones is safe (Takeyama, 2006). Asymptomatic gallstones found at an unrelated open gastrointestinal operation should prompt a cholecystectomy, if exposure is adequate and if the operation can be done safely. In contrast, children with asymptomatic gallstones caused by other etiologies can be safely managed expectantly, and these gallstones have been shown to regress in 17% to 34% of cases (Curro et al, 2007). Finally, gallstones have a proven association with gallbladder carcinoma (Tewari, 2006) (see Chapter 49). In a review of 200 consecutive calculous cholecystitis specimens, AlboresSaavedra and colleagues (1980) reported that 83% exhibited epithelial hyperplasia, 13. In areas endemic for gallbladder cancer, the risk of carcinoma increases with larger gallstones: the relative risk rises from 2. Native Americans and patients with gallbladder calcification also have a higher incidence of gallbladder cancer. Elective cholecystectomy has been recommended in patients with gallstones greater than 3 cm in diameter, but no proof is available to support that such an approach is warranted from an oncologic standpoint (Gupta et al, 2004; Mohandas et al, 2006; Tewari 2006). Symptomatic Gallstones Approximately 30% of patients with gallstones will develop symptoms, and once this occurs, cholecystectomy is usually indicated for both symptomatic improvement and to prevent further complications. The spectrum of severity characterizing symptomatic gallstones ranges from episodic pain to lifethreatening infection and shock (see Chapters 32 and 33). Biliary colic is the most typical clinical presentation of symptomatic gallstones (see Chapter 13). This visceral pain likely reflects the gallbladder contracting against a cystic duct blocked by an impacted gallstone. If pain persists and escalates, it can herald a worse complication of gallstones, such as cholecystitis, cholangitis, or pancreatitis. Pain often remits after several hours, which can create a false sense of security in some patients. More than 60% of patients will suffer recurrent pain within 2 years of their initial attack, and several studies have indicated that gallstoneassociated complications occur more frequently in patients who experience biliary colic. Acute cholecystitis occurs in about 20% of patients with symptomatic gallstones (see Chapter 33). The pathogenesis is prolonged calculous obstruction of the cystic duct with resulting inflammation. The inflamed gallbladder becomes dilated and edematous, manifested by wall thickening, and an exudate of pericholecystic fluid can develop. If the gallstones are sterile, the inflammation is initially sterile, which can occur in patients with cholesterol gallstones. In other cases, however, gallstone formation occurs as a result of bacterial colonization of the biliary tree, rendering pigmented gallstones containing bacterial microcolonies (Stewart et al, 2002). Further, no increase in morbidity is associated with concomitant cholecystectomy (Klaus et al, 2002; Stewart et al, 1989). Studies reported no increase in graft infection or morbidity when cholecystectomy was performed following closure of the retroperitoneum; however, more recent data show similar mortality rates with or without concomitant cholecystectomy. Children with asymptomatic gallstones comprise two main etiologic groups: those with hemolytic anemia (sickle cell disease, -thalassemia, hemoglobinopathies) and those whose cholelithiasis stems from some other cause (total parenteral nutrition, short bowel syndrome, cardiac surgery, leukemia, lymphoma). Expectant management for children with hemolytic anemia is associated with a significant increase in morbidity and postoperative hospital stay, and elective cholecystectomy is therefore recommended (Curro et al, 2007). For patients with sickle cell disease and asymptomatic gallstones, elective cholecystectomy is advised because expectant management yields more than a twofold increase in morbidity.

References

• Shen X, Tomaras GD: Alterations of the B-cell response by HIV-1 replication, Curr HIV/AIDS Rep 8(1):23-30, March 2011.
• Demkow M, Sorenson K, Whitehead BF: Heart transplantation in an infant with rhabdomyoma. Pediatr Cardiol 1995; 16:204-206.
• Roe MT, Staman KL, Pollack C, et al: A practical guide to understanding the 2002 ACC/AHA guidelines for the management of patients with non-ST-segment elevation acute coronary syndromes. Crit Pathways Cardiol 2002;1:129-149.
• Rogers JM. Tobacco and pregnancy: overview of exposures and effects. Birth Defects Res C Embryo Today. 2008; 84(1): 1-15.