William Sanchez
Mayo Clinic
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Gastroenterology | 2013
Siddharth Singh; Preet Paul Singh; Abha G. Singh; Mohammad Hassan Murad; William Sanchez
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Several studies have shown that statins could have chemopreventive effects on HCC. We performed a systematic review and meta-analysis of studies that evaluated the effects of statins on the risk of HCC. METHODS We conducted a systematic search of MEDLINE, Embase, and Web of Science through May 2012 and manually reviewed the literature. Studies were included if they evaluated and clearly defined exposure to statins, reported the incidence of HCC, and reported relative risks or odds ratios (ORs) or provided data for their estimation. Ten studies reporting 4298 cases of HCC in 1,459,417 patients were analyzed. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random effects model. Statistical heterogeneity was assessed with the Cochrans Q statistic and I(2) statistic. RESULTS Statin users were less likely to develop HCC than statin nonusers (adjusted OR, 0.63; 95% CI, 0.52-0.76), although the results were heterogeneous (P = .01, I(2) = 59%). This heterogeneity could be accounted for by study location (Asian population [n = 4]: adjusted OR, 0.52; 95% CI, 0.42-0.64; Western population [n = 6]: adjusted OR, 0.67; 95% CI, 0.53-0.85) and design (observational studies [n = 7]: adjusted OR, 0.60; 95% CI, 0.49-0.73; clinical trials [n = 3]: adjusted OR, 0.95; 95% CI, 0.62-1.45). CONCLUSIONS Based on meta-analysis, statin use is associated with a reduced risk of HCC, most strongly in Asian but also in Western populations. Randomized clinical trials in populations at high risk for HCC (especially in Asian populations with hepatitis B) are warranted.
Nature Reviews Gastroenterology & Hepatology | 2014
Siddharth Singh; Preet Paul Singh; Lewis R. Roberts; William Sanchez
Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer. The incidence and mortality of HCC are increasing in most Western countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Chemopreventive strategies aimed at decreasing the risk or delaying the onset of HCC are needed. Universal immunization against HBV and antiviral therapy against HBV and HCV in patients with established disease has consistently been associated with reduced HCC risk, especially in patients who achieve sustained virologic response. However, the cost-effectiveness of antiviral therapy for primary HCC prevention is not known. Several commonly prescribed medications seem promising as chemopreventive agents against HCC, including statins, antidiabetic medications and aspirin. Dietary agents such as coffee, vitamin E and fish oil as well as phytochemicals might also be associated with reduced risk of HCC. Though randomized controlled trials are ideally needed to firmly establish efficacy, such chemoprevention trials are logistically and ethically challenging. Well-designed, prospective, population-based cohort studies might provide the best evidence for chemopreventive efficacy of these agents.
American Journal of Transplantation | 2013
Julie K. Heimbach; Kymberly D. Watt; John J. Poterucha; N. Francisco Ziller; S. D. Cecco; Michael R. Charlton; J. E. Hay; Russell H. Wiesner; William Sanchez; Charles B. Rosen; James M. Swain
Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post‐LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post‐LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post‐LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post‐LT metabolic complications. Long‐term follow‐up is needed.
The American Journal of Gastroenterology | 2004
William Sanchez; Gavin C. Harewood; Bret T. Petersen
BACKGROUND AND OBJECTIVES:Multiple factors influence the yield of colonoscopy for the detection of neoplasia. Few studies have addressed the impact of colonoscopy duration on procedure yield. The aim of our study was to determine whether endoscopist-specific procedure times correlate with the number and clinical significance of polyps detected at screening or surveillance colonoscopy.METHODS:Procedural data from screening or surveillance colonoscopies performed at Mayo Clinic, Rochester MN, between January 1, 1996 and June 30, 2000, were reviewed. Individual endoscopists were characterized by their personal endoscopist procedure mean time (EPMT) to perform a negative colonoscopy. Procedure time included patients consent and sedation. EPMT was then correlated with individual polyp detection rates.RESULTS:Overall, 10,159 colonoscopies were reviewed of which 4,312 (42.4%) yielded polyps. Polyp detection varied among endoscopists between 19.0% and 62.3%. There was a close correlation between EPMT and polyp yield (all sizes), r = 0.64, although correlation was weaker for polyps >10 mm (r = 0.42) and polyps >20 mm (r = 0.20). On multivariate analysis, longer mean endoscopist time was associated with colonic lesion detection, OR = 1.54 (95% CI 1.37–1.62). Longer mean procedure duration demonstrated a looser association with identification of polyps >10 mm, OR = 1.40 (1.19–1.64) and polyps >20 mm, OR = 1.03 (0.74–1.43).CONCLUSIONS:There is a direct correlation between colonoscopy procedure time and yield, with a three-fold variation of polyp detection rates. These results should prompt future prospective studies assessing the impact of colonoscopic withdrawal time on lesion detection.
Radiology | 2013
Shigao Chen; William Sanchez; Matthew R. Callstrom; Brian Gorman; Jason T. Lewis; Schuyler O. Sanderson; James F. Greenleaf; Hua Xie; Yan Shi; Michael D. Pashley; Vijay Shamdasani; Michael Lachman; Stephen Metz
PURPOSE To investigate the value of viscosity measured with ultrasonographic (US) elastography in liver fibrosis staging and to determine whether the use of a viscoelastic model to estimate liver elasticity can improve its accuracy in fibrosis staging. MATERIALS AND METHODS The study, which was performed from February 2010 to March 2011, was compliant with HIPAA and approved by the institutional review board. Written informed consent was obtained from each subject. Ten healthy volunteers (eight women and two men aged 27-55 years) and 35 patients with liver disease (17 women and 18 men aged 19-74 years) were studied by using US elasticity measurements of the liver (within 6 months of liver biopsy). US data were analyzed with the shear wave dispersion ultrasound vibrometry (SDUV) method, in which elasticity and viscosity are measured by evaluating dispersion of shear wave propagation speed, as well as with the time-to-peak (TTP) method, where tissue viscosity was neglected and only elasticity was estimated from the effective shear wave speed. The hepatic fibrosis stage was assessed histologically by using the METAVIR scoring system. The correlation of elasticity and viscosity was assessed with the Pearson correlation coefficient. The performances of SDUV and TTP were evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS The authors found significant correlations between elasticity and viscosity measured with SDUV (r = 0.80) and elasticity measured with SDUV and TTP (r = 0.94). The area under the ROC curve for differentiating between grade F0-F1 fibrosis and grade F2-F4 fibrosis was 0.98 for elasticity measured with SDUV, 0.86 for viscosity measured with SDUV, and 0.95 for elasticity measured with TTP. CONCLUSION The results suggest that elasticity and viscosity measured between 95 Hz and 380 Hz by using SDUV are correlated and that elasticity measurements from SDUV and TTP showed substantially similar performance in liver fibrosis staging, although elasticity calculated from SDUV provided a better area under the ROC curve.
Hpb | 2011
Julie K. Heimbach; William Sanchez; Charles B. Rosen; Gregory J. Gores
BACKGROUND Hilar cholangiocarcinoma presents both diagnostic and therapeutic challenges. While establishing a diagnosis is important for patients considering aggressive treatment, a transperitoneal fine needle aspiration (FNA) may lead to seeding of the tumour. The aim of the present study was to determine whether patients who have undergone transperitoneal FNA of the primary tumour have a higher incidence of metastases. PATIENTS AND METHODS Outcomes of 191 patients enrolled in a neoadjuvant chemoradiotherapy followed by liver transplantation (LT) from 1 October 1992 to 1 January 2010 were analysed. The incidence of metastases was compared between those who did or did not undergo a transperitoneal FNA biopsy of the primary tumour. RESULTS A total of 16 patients underwent FNA biopsy. There were six patients with biopsies positive for adenocarcinoma and 5/6 (83%) had peritoneal metastases at operative staging. Nine patients had biopsies, which did not demonstrate a tumour, and had no evidence of metastasis. One patient had an equivocal biopsy. Of those who did not undergo a transperitoneal biopsy, the incidence of peritoneal metastasis was 8% (14/175), P= 0.0097 vs. positive staging (83%) in those with a diagnostic transperitoneal FNA. Survival at 5 years for those who underwent LT was 74%. CONCLUSION Transperitoneal biopsy of hilar cholangiocarcinoma is associated with a higher rate of peritoneal metastases, and it should not be performed if a curative approach such as LT is available.
Mayo Clinic Proceedings | 2006
William Sanchez; John T. Maple; Lawrence J. Burgart; Patrick S. Kamath
Dietary supplements containing usnic acid are marketed for weight loss and have been associated with hepatotoxicity. The specific ingredient responsible for the hepatotoxicity is currently unknown. We describe 2 patients who developed severe hepatotoxicity within 3 months of taking a dietary supplement containing usnic acid. One patient developed fulminant hepatic failure requiring emergency liver transplantation; the other developed submassive hepatic necrosis but did not require transplantation. Thorough investigation, including histopathological examination of the liver, revealed no other cause of acute liver injury. Usnic acid hepatotoxicity should be considered as a possible etiologic factor in patients presenting with fulminant hepatic failure, especially if they have been taking dietary supplements for weight reduction.
The American Journal of Gastroenterology | 2014
Roongruedee Chaiteerakij; William S. Harmsen; Carlos Romero Marrero; Mohammed M. Aboelsoud; Albert Ndzengue; Joseph Kaiya; Terry M. Therneau; William Sanchez; Gregory J. Gores; Lewis R. Roberts
OBJECTIVES:Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials.METHODS:Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system.RESULTS:Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1–2.6), 3.1 (2.0–4.7), and 8.7 (5.2–14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival.CONCLUSIONS:This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials.
Current Opinion in Gastroenterology | 2009
Boris Blechacz; William Sanchez; Gregory J. Gores
Cholangiocarcinoma (CCA) is a devastating disease with features of bile duct epithelial differentiation. Considerable progress has been made regarding the imaging characteristics of this disease, diagnostic criteria, surgical approaches and palliative management. Conversely, progress regarding medical therapy for advanced CCA has been limited. The design and implementation of Phase II trials has been hampered by the lack of staging systems to stratify patient populations. Until refined stratification schemes are available, results from Phase II trials, even randomized Phase II trials, will be difficult if not impossible to interpret due to marked patient heterogeneity. In this commentary, we will propose schemes to help stratify patients with CCA based on our current understanding of the disease. Biliary tract malignancies include intrahepatic cholangiocarcinoma, ductal cholangiocarcinoma, gallbladder cancers and cancers of the ampulla of Vater. Often, all of these biliary tract cancer subsets are included in medical trials on biliary tract cancers. However, gallbladder cancers, CCA and cancers of the ampulla of Vater are distinct entities with unique molecular signatures, mechanisms of disease dissemination and natural history. Furthermore, CCA exists as two types of cancer, intrahepatic mass forming cancers and cancers involving the large bile ducts. We propose that these two subsets be defined as intrahepatic CCA and ductal CCA (Table 1). Intrahepatic CCA would be classified as intrahepatic mass lesions without causing bile duct obstruction or jaundice. Ductal CCA would involve cancers of the common bile duct, common hepatic duct, right and/or left hepatic ducts including their secondary bifurcation. Terms such as Klatskin tumor, or perihilar CCA, which is a form of ductal CCA should be discouraged. Likewise, the erroneous classification by the Surveillance, Epidemiology, End Result (SEER) database of perihilar CCA as intrahepatic CCA must be corrected [1]. Biliary tract cancers should not be ‘lumped’ together in clinical trials, but rather examined and treated as individual, distinct subsets of biliary tract cancers. Clinical trials should be limited to each specific subset of these cancers including unique trials for intrahepatic and ductal CCA. Staging systems of gallbladder cancer have been well defined [2,3] and therefore, this cancer population can be appropriately stratified and emerging therapies assessed. Table 1 Proposed classification of cholangiocarcinoma Recently, a staging system for intrahepatic CCA has been proposed [4]. This classification is based on number of intrahepatic lesions, presence or absence of vascular invasion and lymph node metastases. In contrast, there is no proposed staging system for ductal CCA. Prior staging systems such as the Bismuth-Collette and the Memorial Sloan Kettering staging system pertain to selection of patients for surgery but were never meant to correlate with survival and do not pertain to patients with advanced disease [5,6]. The optimal staging system for ductal CCA should take into account the following parameters: the stage of the tumor; magnitude of ductal and vascular obstruction and their functional consequences for hepatic function and selection for surgery; the performance status of the patient; and the availability and effectiveness of therapy. Such a staging system has been developed for hepatocellular carcinoma and has been externally validated [7–10]. The tumor stage should take into account the size of the primary lesion, vascular encasement, the presence or absence of lobar atrophy and extrahepatic spread of the disease. Most primary ductal CCA are difficult to visualize as mass lesions and lack a measurable radial diameter. These neoplasms have a tropism for bile and as such, often encircle and stricture the bile duct causing jaundice. Given this tropism, the cancers also grow longitudinally along the bile duct before growing radially away from the biliary apparatus. Therefore, the identification of mass should be considered as a more advanced cancer than nonvisualized lesions, despite the lack of metastases or a similar clinical presentation (e.g. painless jaundice). We also propose that mass lesions be stratified as 3 cm or less or more than 3 cm based upon our experience. Vascular encasement (a frequent occurrence in this disease) and lobar atrophy (due to longstanding lobar bile duct and/or vascular obstruction) have been identified as adverse prognostic features in surgical studies [5,11]. Such features often suggest a prolonged disease interval between disease development and presentation; a feature favoring sufficient time to develop regional micrometastases. Also, lobar bile duct involvement (e.g. right hepatic duct) with contralateral vascular encasement (e.g. left portal vein encasement) precludes surgical resection, the only established, potentially curative therapy for ductal CCA. Thus, each of these tumor/liver anatomic relationships needs to be incorporated into the staging system. Extrahepatic spread signifies metastases and is always an adverse prognostic finding in any human cancer. CCA has three types of regional metastases: lymphatic spread into regional and more distant lymph nodes; venous invasion with intrahepatic metastases; and peritoneal metastases. Which one of these features portends the more adverse prognosis is not readily apparent and will require further study. Lymph node metastases can be regional with involvement of hilar lymph nodes, periduodenal lymph nodes and/or periaortic lymph nodes. Likely, the more distant the lymph node metastases are from the primary tumor, the worse the prognosis; but again, this is a concept that requires careful validation. Although the presence or absence of lymph node metastases can be difficult to confirm by imaging criteria, the use of endoscopic ultrasound with fine needle aspirates for lymph node cytology has made this distinction more reliable. The ability to relieve cholestasis with placement of biliary stents must also be taken into effect. A recent study suggests that if the bilirubin is less than or equal to 10 mg/dl, jaundice (defined as a serum bilirubin >3 mg/dl) should resolve within 3 weeks [12]. For bilirubin values more than 10mg/dl, it may take 6 weeks to obtain resolution of jaundice. Given these data, the parameters for jaundice resolution would be bilirubin and time-dependent. The inability to relieve jaundice results in impaired liver function secondary to persistent cholestasis and impacts on the overall heath and performance status of the patient. This cholestatic liver dysfunction adversely effects survival and, therefore, is a critical component of the staging system. Also, whether surgical exploration is or is not feasible (the only current therapy) will also affect patient outcomes. Based on this analysis and the rationale developed for HCC, we have assimilated these factors into a proposed staging system (Table 2). Any positive parameter within a column would relegate the patient to this stage. Table 2 Proposed staging system for ductal cholangiocarcinoma This proposed staging system is virtual at this point in time; however, we are in the process of validating this stratification scheme. Perhaps other objective parameters will also help add precision to this staging system (e.g. serum CA19-9 values >1000 U/ml, CCA complicating primary sclerosing cholangitis, etc.). We encourage others to also validate and refine this proposed schema. We also hope this commentary will galvanize a multidisciplinary effort to develop staging systems for this disease, perhaps lead by a major society (e.g. the American Association for the Study of Liver Diseases, American Society of Clinical Oncology, etc.). Only once such a staging system has been validated can randomized Phase II trials be reliably conducted with more homogenous patient populations for ductal CCA. This is a pressing need as promising targeted therapies are being developed and need to be applied to this subset of biliary tract cancers.
American Journal of Transplantation | 2014
D. J. Kim; Paul J. Clark; Julie K. Heimbach; Charles B. Rosen; William Sanchez; Kymberly D. Watt; Michael R. Charlton
Determining risk for recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) is an important clinical need. We assessed consecutive patients who underwent LT for HCC following sequential transarterial chemoembolization (TACE). Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Cox proportional hazard models were used to predict HCC recurrence. One hundred seventy‐three patients underwent TACE and imaging to assess response prior to LT. TACE responses were: CR = 23.7%, PR = 24.3%, SD = 27.7% and PD = 24.3%. Five‐year HCC recurrence rate was 5.3% in patients responding to TACE (CR/PR), versus 17.6%, among patients who did not respond (SD/PD, p = 0.014). In multivariate analysis, independent pre‐LT predictors of recurrence were response to TACE and largest radiologic size of tumor (>3 cm vs. ≤3 cm). HCC recurrence rate for patients with tumor size >3 cm and no response to TACE was 35.8%, compared with 1.9% for patients with tumor size ≤3 cm and response to TACE (p = 0.0007). We conclude that mRECIST criteria and tumor size differentiate patients with high or low likelihood of HCC recurrence after LT. These findings raise the possibility of incorporating response to TACE and largest tumor size to identify patients at highest risk for HCC recurrence.