Chronic Acalculous Cholecystitis Research Articles

Nuclear medicine hepatobiliary imaging (cholescintigraphy)

Nuclear medicine hepatobiliary imaging (cholescintigraphy)

New American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidism: Significant Progress for the Clinician and a Guide to Future Research

New American Thyroid Association and American Association of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidism: Significant Progress for the Clinician and a Guide to Future Research

Diagnosis and surgical treatment of chronic acalculous cholecystitis characterized by absence of gallbladder wall contractability in 42 cases

Objective To investigate the diagnosis and surgical treatment of chronic acalculous cholecystitis characterized by absence of gallbladder wall contractability. Methods The clinical data of 42 patients with chronic acalculous cholecystitis in our hospital from January 2006 to December 2008were analysed. The patients were grouped into two groups: laparoscopic cholecystectomy (LC) group in 20 and non-surgical group in 22. The patients' symptoms on follow-up in the two groups were compared. Results The 42 patients with chronic acalculous cholecystitis were diagnosed by symptoms,ultrasound, fatty meal gallbladder contractability studies under ultrasound, fiber optic gastroscopy and magnetic resonance cholangiopancreatography (MRCP). In all patients, there was a complete absence of gallbladder wall contractability. In the LC groups, 20 patients received LC. 18 patients were followed up, and there were no symptoms. Two patients were lost to follow up. In the non-surgical group, 22 patients received non-surgical treatment. In 21 patients who were followed up, 19 patients had symptoms. One patient was lost to follow up. There was a significant difference between the LC group and the non-surgical group (P＜0.05). Conclusions Chronic acalculous cholecystitis characterized by absence of gallbladder wall contractability could be diagnosed by symptoms, ultrasound, fatty meal gallbladder contractability studies under untrasound, and MRCP. The optimal treatment of chronic acalculous cholecystitis characterized by absence of gallbladder wall contractability is LC. Key words: Cholecystitis; Cholecystectomy; Laparoscopic; Gallbladder contractability; Magnetic resonance cholangiopancreatography

Reproducibility of gallbladder ejection fraction measured by Fatty meal cholescintigraphy.

There are conflicting data in the literature regarding the reproducibility of the gallbladder ejection fraction (GBEF) measured by fatty meal cholescintigraphy (CS). We aimed to test the reproducibility of GBEF measured by fatty meal CS. Thirty-five subjects (25 healthy volunteers and 10 patients with chronic abdominal pain) underwent fatty meal CS twice in order to measure GBEF1 and GBEF2. The healthy volunteers underwent a repeat scan within 1-13months from the first scan. The patients underwent a repeat scan within 1-4years from the first scan and were not found to have chronic acalculous cholecystitis (CAC). Our standard fatty meal was composed of a 60-g Snickers chocolate bar and 200ml full-fat yogurt. The mean ± SD values for GBEF1 and GBEF2 were 52 ± 17% and 52 ± 16%, respectively. There was a direct linear correlation between the values of GBEF1 and GBEF2 for the subjects, with a correlation coefficient of 0.509 (p = 0.002). Subgroup data analysis of the volunteer group showed that there was significant linear correlation between volunteer values of GBEF1 and GBEF2, with a correlation coefficient of 0.473 (p = 0.017). Subgroup data analysis of the non-CAC patient group showed no significant correlation between patient values of GBEF1 and GBEF2, likely due to limited sample size. This study showed that fatty meal CS is a reliable test in gallbladder motility evaluation and that GBEF measured by fatty meal CS is reproducible.

Molecular characterization of Cystoisospora belli and unizoite tissue cyst in patients with Acquired Immunodeficiency Syndrome

Cystoisospora belli is a coccidian protozoan that can cause chronic diarrhoea, acalculous cholecystitis and cholangiopathy in AIDS patients. We applied molecular methods to identify Cystoisospora at species level in AIDS patients presenting with and without the presence of unizoites in lamina propria. Coprological and histological analyses were performed in stool and/or biopsy samples from 8 Cystoisospora-infected patients. DNA from the same samples was used to amplify 2 fragments of the SSU-rRNA gene and the ITS-1 region. Sequencing of the resulting amplicons identified C. belli infections in all cases, independent of the presence or absence of unizoite tissue cysts. Further work should be considered in order to find molecular targets related to strain variations in C. belli.

Gallbladder ejection fraction measured by fatty meal cholescintigraphy: is it affected by extended gallbladder emptying data acquisition time?

The main objective of this study was to determine the effect of gallbladder emptying acquisition time on gallbladder ejection fraction (GBEF) measurement obtained by fatty meal cholescintigraphy (CS). During fatty meal cholescintigraphy (CS), GBEF1 and GBEF2 were calculated 20 and 45 min, respectively, post meal ingestion on 50 healthy volunteers, 37 patients with chronic acalculous cholecystitis (CAC) and 20 non-CAC patients. GBEF1/GBEF2 was calculated and represented the percentage of GBEF occurred during 20 min after meal ingestion. The gallbladder was classified as ended pattern if it terminated contraction before the end of data acquisition or classified as continuous pattern if it continued to contract before the end of data acquisition. Mean GBEF in continuous pattern was compared with mean GBEF in ended pattern in each group. Gallbladder emptying had two phases; early rapid phase and late slow phase. About two-thirds of ejected volume occurred within the rapid phase. About half of gallbladders in each group were classified as ended pattern while the other half was classified as continuous pattern. There was no significant difference in mean GBEF values between both patterns in each group. GBEF measurement obtained by CS is not affected by further extension of gallbladder emptying data acquisition beyond the standard 45-60 min acquisition time.

Diagnostic value of gallbladder emptying variables in chronic acalculous cholecystitis as assessed by fatty meal cholescintigraphy

The main purpose of this study was to determine the diagnostic value of gallbladder emptying variables in chronic acalculous cholecystitis (CAC). The variables investigated were latent period, gallbladder ejection fraction (GBEF) and patterns of gallbladder emptying. In addition, two other biliary system motility variables were investigated including the onset of gallbladder filling and biliary-to-bowel transit time. Thirty-nine healthy volunteers underwent fatty meal cholescintigraphy (CS) prospectively to determine the normal values of these variables. Retrospectively, fatty meal CS studies of 88 patients suspected of having CAC were retrieved and reprocessed to obtain corresponding values of these variables, which then compared with normal values. The mean onset of gallbladder filling for patient groups was not significantly different from volunteer group mean. The mean+/-SD GBEF value for CAC group (29+/-20%) was significantly lower than volunteer group value (54+/-23%), whereas for non-CAC group (60+/-21%) it was not significantly different. The latent period was found invariable and not significant in CAC diagnosis. Two patterns of gallbladder emptying were noted: ended and continuous. The pattern of gallbladder emptying did not affect the mean GBEF and was found insignificant in the diagnosis of CAC. There was no significant difference in the number of cases with late biliary-to-bowel transit time between the groups. The single most important gallbladder emptying variable in diagnosing CAC is the GBEF. The latent period and the pattern of gallbladder emptying as well as the onset of gallbladder filling and biliary-to-bowel transit time are of no significant diagnostic value in CAC.

Usefulness of fatty meal-stimulated cholescintigraphy in the diagnosis and treatment of chronic acalculous cholecystitis

Fatty meal cholescintigraphy (fatty meal CS) is a potential physiologic alternative for cholecystokinin (CCK) CS in the diagnosis and treatment of chronic acalculous cholecystitis (CAC). However, there are limited data in the literature to support this assumption. Our objective was to determine the usefulness of fatty meal CS in the diagnosis and treatment of CAC. We retrospectively reviewed the medical records of 198 patients who had undergone fatty meal CS for presumed CAC. Data retrieved focused on symptom improvement following management. Gallbladder ejection fraction (GBEF) of 50% or less was considered abnormal. Patients were divided into groups on the basis of test results and management. In group 1a, patients with low GBEF and cholecystectomy, 88% (54 of 61) reported symptom improvement, whereas the remaining 12% (7 of 61) retained their symptoms. Group 1b consisted of patients with low GBEF and who were managed medically. Persistence of symptoms was noted in 76% (32 of 42) of patients, whereas the remaining 24% (10 of 42) had symptom improvement. Group 2 consisted of patients with normal GBEF. Follow-up showed that 60% (47 of 78) of patients had symptom improvement either spontaneously or on medical treatment, whereas the remaining 40% (31 of 78) retained their symptoms. Fatty meal CS is a very useful technique in the diagnosis of CAC. It predicts a good surgical outcome once GBEF is low in patients with high pre-test probability for CAC. Moreover, fatty meal CS may be a good alternative to CCK CS.

Cholecystitis After Trauma

The goal of this project was to investigate incidence, risk factors, histologic findings, and mortality rate of posttraumatic cholecystitis requiring surgical treatment. Retrospective analysis of all patients admitted to the intensive care unit of an urban trauma center between April 1998 and January 2005. Data from the hospital and intensive care documentation systems databases and patients' charts were reviewed. All patients with cholecystitis treated by cholecystectomy were selected for further study. Potential risk factors, diagnostic, and histologic findings were analyzed. Cholecystitis was a fairly frequent finding in critically ill trauma patients (67 of 2,625 patients, 2.6%). Almost 10% of the patients with severe multiple injuries developed cholecystitis. Histologic findings showed a wide variation; three main diagnoses were established: acute acalculous cholecystitis (n = 28), chronic acalculous cholecystitis (n = 25), and cholecystitis with cholecystolithiasis (n = 13). Patients with acute acalculous cholecystitis and chronic acalculous cholecystitis were significantly younger and had significantly higher injury severity scores than patients with either cholecystitis with cholecystolithiasis or without cholecystitis. Noninvasive diagnostic tools such as ultrasonographic signs and laboratory data did not correlate with histologic diagnosis. Well-timed cholecystectomy within 24 hours after clinical suspicion lead to a 4.4% mortality rate in this group of patients. Cholecystitis after trauma is not a uniform disease. Although trauma severity seems to play an important role in the development or exacerbation of acalculous cholecystitis or both, cholecystolithiasis may play a significant role in patients with moderate to minor trauma. Intensivists should be aware of this complication in critically ill trauma patients because it seems to occur more frequently than previously assumed. Diagnosis can only be made if clinical signs, laboratory data, and ultrasonographic findings are taken into consideration. If posttraumatic cholecystitis is treated in an early stage by cholecystectomy, mortality rate remains low.

Steatocholecystitis and Fatty Gallbladder Disease

Obesity has become an epidemic worldwide. It is accompanied by a multitude of medical complications including metabolic syndrome. Obesity may lead to fatty infiltration of multiple internal organs including liver, heart, kidney, and pancreas, causing organ dysfunctions. Fatty infiltration leads to chronic inflammation and tissue damage. Fatty infiltration in the liver results in nonalcoholic fatty liver disease, which is increasingly common nowadays. Recent studies in animals and humans indicate that obesity also is associated with fatty infiltration of gallbladder, resulting in cholecystosteatosis. The increased gallbladder lipids include free fatty acids, phospholipids, and triglycerides. Enhanced inflammation with an increased amount of fat in the gallbladder results in an abnormal wall structure and decreased contractility. In support of this notion, a recent experiment on the effect of Ezetimibe, which is a novel drug that inhibits intestinal fat absorption, on fatty gallbladder disease reveals that Ezetimibe can ameliorate cholecystosteatosis and restore in vivo gallbladder contractility. The proportion of cholecystectomies performed for chronic acalculous cholecystitis has increased significantly over the past two decades. An increase in gallbladder fat, which leads to poor gallbladder emptying and biliary symptoms, may partly explain this phenomenon. Although dietary carbohydrates have been demonstrated to be associated with fatty gallbladder disease, other potential modifiable environmental factors are not clear. The pathogenesis and prognosis of fatty gallbladder disease, including steatocholecystitis, and the relations of fatty gallbladder disease to nonalcoholic fatty liver disease, including steatohepatitis, and other components of metabolic syndrome are largely unknown. More research is needed to answer these questions.

T1697 Outcomes of Endoscopic and Surgical Management of Sphincter of Oddi Dyskinesia in Patients Not Responding to Cholecystectomy for Chronic Acalculous Cholecystitis

T1697 Outcomes of Endoscopic and Surgical Management of Sphincter of Oddi Dyskinesia in Patients Not Responding to Cholecystectomy for Chronic Acalculous Cholecystitis

Hepato-pancreato-biliary fat: the good, the bad and the ugly

Obesity has become epidemic in the United States, in Europe, and in many urban areas in the developing world. The globalization of certain ‘fast foods’ and ‘soft drinks’ may, in part, be contributing to this epidemic. Diets high in saturated fatty acids and trans fats as well as drinks that have high fructose corn syrup levels may be particularly harmful. Recent research suggests that fat is a dynamic endocrine organ and that visceral fat is associated with the metabolic syndrome. Central obesity leads to organ steatosis and altered serum adipokines including reduced adiponectin and markedly elevated leptin. This abnormal adipokine milieu results in increased tissue infiltration of monocytes and macrophages which produce proinflammatory cytokines that alter organ function. Over many years, the combination of steatosis and local inflammation leads to fibrosis and eventually to cancer. Nonalcoholic fatty liver disease (NAFLD) is a precursor for nonalcoholic steatohepatitis (NASH). NAFLD and NASH (1) lead to cirrhosis and hepatocellular carcinoma, (2) increase the risk of liver resection, and (3) compromise the outcome of liver transplantation. Similarly, in the pancreas nonalcoholic fatty pancreas disease (NAFPD) may lead to nonalcoholic steatopancreatitis (NASP). NAFPD and NASP may (1) promote the development of chronic pancreatitis and pancreatic cancer, (2) exacerbate the severity of acute pancreatitis, and (3) increase the risk of pancreatic surgery. In the gallbladder nonalcoholic fatty gallbladder disease (NAFGBD, cholecystosteatosis) may lead to steatocholecystitis. Cholecystosteatosis may be an explanation for (1) the increased incidence of chronic acalculous cholecystitis and (2) the increased number of cholecystectomies.

HIDA scan ejection fraction does not predict sphincter of Oddi hypertension or clinical outcome in patients with suspected chronic acalculous cholecystitis

Hepatobiliary iminodiacetic scan with ejection fraction (HIDA EF) is used to evaluate chronic acalculous cholecystitis (CAC). A presumed etiology of CAC is sphincter of Oddi hypertension (SOH). In this study, we evaluated the value of HIDA EF to predict patient response to laparoscopic cholecystectomy and to identify SOH. A prospective study of 93 patients with biliary pain but without gallstones (CAC) who underwent preoperative HIDA EF was conducted. At laparoscopic cholecystectomy, transcystic antegrade biliary manometry was performed to determine the SO pressure. Patients were evaluated postoperatively for response to cholecystectomy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The outcomes were compared with the clinical impression. Of the 93 patients with both HIDA EF and SOP measurements, 50 had abnormal EF (< 35%); of these, 29 had SOH (SO pressure > or = 40 mmHg). Of the 43 patients with normal HIDA EF, 30 had SOH. The sensitivity was 49%, specificity 38%, PPV 58%, and NPV 30%. Eighty-six of the 93 patients returned for follow-up evaluation. Follow-up ranged from 0 to 99 months, with a mean of 26.4 months. Overall, 73 patients (85%) improved. Of the 46 with abnormal HIDA EF, 42 (91%) improved. Of the 40 patients with normal HIDA EF, 31 (77.5%) improved. The sensitivity was 57.7%, specificity 69.2%, PPV 91.3%, and NPV 22.5%. Although the PPV of abnormal HIDA EF is high, it is not much better than the clinical impression. The sensitivity and specificity are marginal. The NPV is poor. Based on the review of these 93 patients, HIDA EF is not reliable for identifying CAC. We recommend that patients with normal HIDA EF have additional testing or consultation before ruling out CAC. HIDA EF does not predict SOH.

Nonalcoholic Fatty Gallbladder Disease: The Influence of Diet in Lean and Obese Mice

The obesity epidemic has contributed to an increased prevalence of gallstones and a higher percentage of chronic acalculous cholecystitis. Obesity is associated with Type II diabetes and hyperlipidemia in murine models. In addition, we have previously demonstrated that serum glucose, insulin, cholesterol, and triglycerides correlated with gallbladder contractility in murine models. However, the relative role of insulin resistance and gallbladder fat infiltration in this phenomenon remain unclear. Therefore, we tested the hypothesis that gallbladder wall lipids are related to obesity and diet and are inversely correlated with gallbladder contractility. One hundred lean control (C7BL/6J) and 36 obese leptin-deficient (Lep(ob)) 8-week-old female mice were fed either a chow diet or a 1.0% cholesterol, 15% butterfat (high-lipid) diet for four weeks. Pooled gallbladders were then analyzed for free fatty acids (FFA), phospholipids (PL), total cholesterol (TC), and triglycerides (TG). Cholesterol/phospholipid ratios were then calculated. The Lep(ob) mice fed a chow diet had significantly higher (P < 0.01) gallbladder lipids than the three other groups. The lean mice that were fed a high-lipid diet had increased (P < 0.05) gallbladder TC compared to the lean mice on a chow diet. In addition, the cholesterol/phospholipid ratio was significantly increased (P < 0.01) in the lean mice fed a high-lipid diet compared to the other three groups. Finally, the high-lipid diet decreased gallbladder FFA (P < 0.01), PL (P = 0.08), and TC (P < 0.05) in Lep(ob) mice. These data suggest that (1) obese mice have increased gallbladder lipids; (2) a high-cholesterol, high-fat diet increases gallbladder lipids and the cholesterol/phospholipid ratio in lean mice; but (3) decreases gallbladder fatty acids, phospholipids, and cholesterol in obese mice. Prior studies have documented similarly decreased gallbladder response to neurotransmitters in obese mice on a chow diet, as well as lean and obese mice on a high-lipid diet. Therefore, we conclude that leptin-deficient obesity and/or a high-fat diet causes nonalcoholic fatty gallbladder disease, which is manifested by diminished gallbladder contractility.

무결석성(無結石性) 만성담낭염(慢性膽囊炎)(Chronic Acalculous Cholecystitis) 환자 치험례

Chronic acalculous cholecystitis gets possession of about 12 to 13 percent of patients with chronic cholecystitis. Pathologically it is characterised by chronic inflammation and thickening of the gallbladder wall but doesn`t come across stones. Clinical symptoms are vague and include abdominal discomfort and distension, nausea, flatulence and intolerance of fatty foods. A patient on chronic acalculous cholecystitis diagnosed from his clinical symtoms and abdominal ultrasonogram was treated by Geonbihwan, acupuncture and herbal acupuncture. Satisfactory symptomatic improvement was achieved and findings of abdominal ultrasonogram came also normal.

Efficacy of an autonomic electronic stimulator of the gastrointestinal tract in patients with chronic acalculous cholecystitis

Efficacy of an autonomic electronic stimulator of the gastrointestinal tract in patients with chronic acalculous cholecystitis

Diagnostic conscious pain mapping using laparoscopy under local anaesthetic and sedation in general surgical patients

Patients in whom extensive investigations have failed to identify the cause of abdominal pain present a challenge to surgeons. We present our initial experience of using laparoscopy under local anaesthetic and sedation in the diagnosis of chronic abdominal pain. Nine patients with chronic abdominal pain and multiple normal investigations underwent laparoscopy under local anaesthetic and sedation. By touching and grasping intra-abdominal viscera and peritoneum, an attempt was made to reproduce the patient's pain. Two patients were found to have pain arising from the gall bladder and subsequently underwent laparoscopic cholecystectomy with resolution of their symptoms. A third patient had a clinical presentation of chronic acalculous cholecystitis and a normal laparoscopy. She decided to undergo laparoscopic cholecystectomy, which cured her pain. Another patient had pain arising from the appendix, which resolved after an appendicectomy. Three patients had pelvic adhesions, which caused chronic abdominal pain. After adhesiolysis, one is pain free; the others declined surgery for adhesions and their pain resolved. Conscious pain mapping was negative in two patients. Laparoscopy can be carried out in the conscious patient, who is then usually able to collaborate with the surgeon in establishing the source of the pain experienced during conscious pain mapping. Long-term effectiveness and diagnostic accuracy has not yet been established.

Stimulation with fatty meal (Lipomul) to assess gallbladder emptying in children with chronic acalculous cholecystitis.

Chronic acalculous cholecystitis previously has been diagnosed by hepatobiliary scan stimulated with intravenous octapeptide of cholecystokinin. This compound may soon be unavailable in the United States. The goal of this study was to describe the characteristics of children with chronic acalculous cholecystitis diagnosed by hepatobiliary scintigraphy with oral Lipomul challenge, and to evaluate their clinical response to cholecystectomy. Retrospective chart review of patients with no gall stones detected by abdominal ultrasound or computed tomography with gallbladder ejection fraction (GBEF) <35% after Lipomul challenge who subsequently underwent cholecystectomy. Fifteen patients with a mean age of 14.9 +/- 0.9 years were included. The mean duration of symptoms before evaluation was 8.2 +/- 2.5 months. The mean GBEF after Lipomul challenge was 16.7% +/- 2.7%. All patients had abdominal pain. Ninety percent had right upper quadrant pain and 86% had typical biliary colic. Pain was precipitated by fatty meals in 73.3%. Histopathologic analysis of the gallbladder demonstrated chronic cholecystitis in 80% of cases. The mean postoperative follow-up was 20 +/- 5 months. Six months after the surgery, nine patients (60%) were asymptomatic, five (33%) had marked improvement of symptoms, and one (6%) was unchanged. At the time of latest follow-up, symptoms had reappeared in two patients who had been asymptomatic at the 6-month visit (13%). Seven patients (46%) remained asymptomatic, five (33%) had marked improvement but continued to have some persistent symptoms, and one (6%) was unchanged. Chronic acalculous cholecystitis may be responsible for right upper quadrant pain in children without gallstones. A GBEF <35% at 30 minutes after Lipomul challenge may be useful in identifying patients who could benefit from cholecystectomy. Lipomul may be a good alternative to cholecystokinin for gallbladder stimulation during scintigraphy.

Stimulation with Fatty Meal (Lipomul) to Assess Gallbladder Emptying in Children with Chronic Acalculous Cholecystitis

ABSTRACTObjectiveChronic acalculous cholecystitis previously has been diagnosed by hepatobiliary scan stimulated with intravenous octapeptide of cholecystokinin. This compound may soon be unavailable in the United States. The goal of this study was to describe the characteristics of children with chronic acalculous cholecystitis diagnosed by hepatobiliary scintigraphy with oral Lipomul challenge, and to evaluate their clinical response to cholecystectomy.MethodsRetrospective chart review of patients with no gall stones detected by abdominal ultrasound or computed tomography with gallbladder ejection fraction (GBEF) &lt;35% after Lipomul challenge who subsequently underwent cholecystectomy. Fifteen patients with a mean age of 14.9 ± 0.9 years were included. The mean duration of symptoms before evaluation was 8.2 ± 2.5 months.ResultsThe mean GBEF after Lipomul challenge was 16.7% ± 2.7%. All patients had abdominal pain. Ninety percent had right upper quadrant pain and 86% had typical biliary colic. Pain was precipitated by fatty meals in 73.3%. Histopathologic analysis of the gallbladder demonstrated chronic cholecystitis in 80% of cases. The mean postoperative follow‐up was 20 ± 5 months. Six months after the surgery, nine patients (60%) were asymptomatic, five (33%) had marked improvement of symptoms, and one (6%) was unchanged. At the time of latest follow‐up, symptoms had reappeared in two patients who had been asymptomatic at the 6‐month visit (13%). Seven patients (46%) remained asymptomatic, five (33%) had marked improvement but continued to have some persistent symptoms, and one (6%) was unchanged.ConclusionsChronic acalculous cholecystitis may be responsible for right upper quadrant pain in children without gallstones. A GBEF &lt;35% at 30 minutes after Lipomul challenge may be useful in identifying patients who could benefit from cholecystectomy. Lipomul may be a good alternative to cholecystokinin for gallbladder stimulation during scintigraphy.

Transcystic biliary manometry to evaluate sphincter of oddi dysfunction in chronic acalculous cholecystitis

Relative apoptosis in HepG2 cells was increased with U0126 alone or in combination with NS398 (9-10X control). Relative apoptosis in both cell lines was strongly correlated with changes in the expression of the anti-apoptotic protein Bcl-xL Cellular growth was assessed by colorimetric proliferation assay and confirmed by cell counts (trypan blue exclusion). HepG2 and Hep3B cells had concentration-dependent inhibition of cell growth with NS398 or U0126 treatment alone. The combination of NS398 and U0126 resulted in additive inhibitory effects on growth. Growth inhibitory effects in HepG2 and Hep38 cells appear to be in part secondary to the induction of GO/G1 and G2/M cell cycle arrest respectively, as determined by flow cytometry. Despite differential signaling in HepG2 and Hep3B cells, the sum effect of combining a COX-2 inhibitor and a MEK inhibitor results in enhanced anti-tumor actions. This novel combination may be useful for treating patients with HCC.