Surakit Pungpapong

Minimally invasive endoscopic staging of suspected lung cancer.

CONTEXT In patients with suspected lung cancer, the presence of mediastinal lymph node metastasis is a critical determinant of therapy and prognosis. Invasive staging with pathologic confirmation is recommended. Many methods for staging exist; mediastinoscopy, an invasive procedure requiring general anesthesia, is currently regarded as the diagnostic standard. OBJECTIVE To compare the diagnostic accuracy of 3 methods of minimally invasive endoscopic staging (and their combinations): traditional transbronchial needle aspiration (TBNA), endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA), and transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In particular, we aimed to compare EBUS-FNA with TBNA. DESIGN, SETTING, AND PARTICIPANTS Invasive staging of the mediastinum among consecutive patients with suspected lung cancer at a US academic medical center from November 2004 through October 2006. INTERVENTION TBNA, EBUS-FNA, and EUS-FNA performed sequentially as a single combined procedure. MAIN OUTCOME MEASURE Sensitivity for detecting mediastinal lymph node metastases, using pathologic confirmation and 6- to 12-month clinical follow-up as the criterion standard. RESULTS Among 138 patients who met all study criteria, 42 (30%) had malignant lymph nodes. EBUS-FNA was more sensitive than TBNA, detecting 29 (69%) vs 15 (36%) malignant lymph nodes (P = .003). The combination of EUS-FNA and EBUS-FNA (EUS plus EBUS) had higher estimated sensitivity (93% [39/42]; 95% confidence interval, 81%-99%) and negative predictive value (97% [96/99]; 95% confidence interval, 91%-99%) compared with either method alone. EUS plus EBUS also had higher sensitivity and higher negative predictive value for detecting lymph nodes in any mediastinal location and for patients without lymph node enlargement on chest computed tomography. CONCLUSIONS These findings suggest that EBUS-FNA has higher sensitivity than TBNA and that EUS plus EBUS may allow near-complete minimally invasive mediastinal staging in patients with suspected lung cancer. These results require confirmation in other studies but suggest that EUS plus EBUS may be an alternative approach for mediastinal staging in patients with suspected lung cancer.

Natural History of Hepatitis B Virus Infection: An Update for Clinicians

Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Significant progress has been made in the past few decades in understanding the natural history of HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. In immunocompetent adults, most HBV infections spontaneously resolve, whereas in most neonates and infants they become chronic. Those with chronic HBV may present in 1 of 4 phases of infection: (1) in a state of immune tolerance, (2) with hepatitis B e antigen (HBeAg)positive chronic hepatitis, (3) as an inactive hepatitis B surface antigen carrier, or (4) with HBeAg-negative chronic hepatitis. Of these, HBeAg-positive and HBeAg-negative chronic hepatitis may progress to cirrhosis and its long-term sequelae including hepatic decompensation and hepatocellular carcinoma. Several prognostic factors, such as serum HBV DNA concentrations, HBeAg status, serum aminotransferases, and certain HBV genotypes, have been identified to predict long-term outcome. These data emphasize the importance of monitoring all patients with chronic HBV infection to identify candidates for and select optimal timing of antiviral treatment, to recognize those at risk of complications, and to implement surveillance for early detection of hepatocellular carcinoma.

Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 after liver transplant.

Treatment with an all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non–liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3‐F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV‐based regimens) received treatment and were followed for a median of 30 weeks (range 12‐53 weeks). The median time from LT to treatment was 32 months (range 2‐317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%‐96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3‐F4 (71%) compared to those with F0‐F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug‐induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention. Conclusion: An all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection. (Hepatology 2015;61:1880–1886)

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole‐to‐cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021‐1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368‐21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole‐to‐cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts. Liver Transpl 18:101–112, 2012.

Accuracy of endoscopic ultrasonography and magnetic resonance cholangiopancreatography for the diagnosis of chronic pancreatitis : A prospective comparison study

Background The diagnosis of chronic pancreatitis (CP) remains challenging. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) have been proposed as highly accurate diagnostic modalities. Although endoscopic retrograde cholangiopancreatography (ERCP) has been previously used as a gold standard, it is associated with a small but significant risk. We aim to compare the accuracy of EUS and MRCP with the composite gold standard using ERCP, surgical pathology, and/or long-term clinical follow-up. Methods Ninety-nine patients with clinical signs and/or symptoms suggestive of CP were prospectively enrolled. The diagnosis of CP by MRCP was established when one or more of these features were present: main duct dilation without obstruction, dilated side branches, intraductal stones, ductal irregularity, reduced T1-signal intensity, parenchymal atrophy, and reduced secretory response to secretin administration. The diagnosis of CP by EUS was made when 4 or more of the established criteria were present. Accuracy of all criteria used (“EUS only,” “MRCP only,” “either EUS or MRCP,” and “both EUS and MRCP”) was compared with the composite gold standard. Results Forty patients were diagnosed with CP by the composite gold standard whereas the remaining 59 patients were controls. EUS only seemed more sensitive but equally specific compared with MRCP only to diagnose CP. The combination of EUS and MRCP had a sensitivity of 98% for either EUS or MRCP and a specificity of 100% for both EUS and MRCP. Conclusions EUS and MRCP are highly accurate modalities for the diagnosis of CP and are complementary when used together. If confirmed in larger series, the diagnosis of CP by both EUS and MRCP is highly predictive and ERCP is unlikely to add any useful information.

Perceptions of Gastroenterology Fellows Regarding ERCP Competency and Training

BACKGROUND The adequacy of ERCP training in the United States may be suboptimal because many training programs do not provide fellows with the exposure to the procedures necessary to achieve competence. METHODS A short survey questionnaire, which assesses the training program, the personal ERCP experience, the perceptions regarding training adequacy, and the post-training practice plans, was sent to all fellows graduating from gastroenterology training programs. RESULTS Graduating fellows performed a median of 140 ERCPs and 35 sphincterotomies during training, with an associated median comfort level for independently performing sphincterotomy of 7.5 on a scale of 1 to 10. The median estimated success rate for independent free cannulation was 75%. Based on nonparametric correlation and regression analysis, 180 ERCPs would be necessary to achieve a free cannulation rate of 80% and 69 sphincterotomies to achieve a comfort level of 8 on a scale of 1 to 10. Thirty-six percent of fellows achieved the number of procedures and cannulation success determined by this study to indicate procedural competence. Sixty-four percent of fellows did not achieve procedural competence and 33% reported inadequate ERCP training. Nevertheless, 91% of fellows expected to perform unsupervised ERCP after training. CONCLUSIONS The results of this study are consistent with those of previously published studies demonstrating that 160 to 200 ERCP procedures are necessary to achieve competence to perform ERCP. The majority of graduating fellows do not achieve an acceptable success rate during training, yet still intend to perform ERCP after training.

Vascular Resection and Reconstruction for Pancreatic Malignancy: A Single Center Survival Study

IntroductionPancreatic cancer is one of the leading causes of cancer-related death in the USA. Recently, several centers have introduced portal and superior mesenteric vein resection and reconstruction during extended pancreatectomy, rendering the previously inoperable cases resectable.AimThe aim of this study is to confirm whether patients with locally advanced pancreatic cancer and mesenteric vascular invasion can be cured with extended pancreatectomy with vascular reconstruction (VR) and to compare their survival to patients treated with pancreatectomy without VR and those treated without resection (palliation).MethodsSurvival of 22 patients who underwent pancreatectomy with VR was compared with two control groups: 54 patients who underwent pancreatectomy without the need for VR and 28 patients whose pre-operative imaging suggested resectability but whose laparotomy indicated inoperability.ResultsA slight survival benefit was noted in patients who did not require VR (33.5%) compared to those who did require VR [20%, p = 0.18], although not reaching statistical significance. Despite a low 15% three-year survival in patients treated palliatively, this was not statistically different compared to survival after resection with VR (P = 0.23). The presence of nodal metastasis was associated with worse survival (p = 0.006), and the use of adjuvant therapy was associated with better survival (p = 0.001).ConclusionPancreatic cancers that require VR to completely resect the tumor have a similar survival to those not requiring VR. Long-term survival was achievable in approximately 1 out 5 patients requiring VR, although we were not able to demonstrate statistically improved survival compared to palliative care.

Risk factors for hyperechogenic pancreas on endoscopic ultrasound: A case-control study

Objective: Hyperechogenic pancreas (HP) suggestive of fatty replacement is a common finding during endoscopic ultrasound (EUS). Recent data have implicated pancreatic steatosis as a risk factor for pancreatitis and pancreatic malignancy. Hepatic steatosis has been linked to obesity, increased age, hypertriglyceridemia, hyperglycemia, and hyperinsulinemia. The objective of this study was to evaluate the effect of body mass index (BMI), hepatic steatosis, and other metabolic risk factors on HP seen on EUS. Methods: Patients with HP were identified by a review of a structured EUS database. The degree of echogenicity was judged relative to the liver (or spleen if the liver is hyperechogenic) at a similar depth. Various demographic and metabolic risk factors were assessed. Chronic pancreatitis was excluded based on normal findings on prior imaging studies. Each case was age matched and sex matched to 1 control with a normal pancreas on EUS. Results: By multivariate logistic regression analysis, BMI, hepatic steatosis, and alcohol use in excess of 14 g/wk were highly associated with the presence of HP compared with controls (all P < 0.002). Hepatic steatosis was the strongest predictor with an odds ratio of nearly 14-fold. Conclusions: Hepatic steatosis, alcohol use, and increased BMI are predictors of HP, which can be a marker for steatosis.

Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C

Although recurrent hepatitis C virus (HCV) after liver transplantation (LT) is universal, a minority of patients will develop cirrhosis within 5 years of surgery, which places them at risk for allograft failure. This retrospective study investigated whether 2 serum fibrosis markers, serum hyaluronic acid (HA) and YKL‐40, could be used to predict rapid fibrosis progression (RFP) post‐LT. These markers were compared with conventional laboratory tests, histological assessment, and hepatic stellate cell activity (HSCA), a key step in fibrogenesis, as assessed by immunohistochemical staining for alpha‐smooth muscle actin. Serum and protocol liver biopsy samples were obtained from 46 LT recipients at means of 5 ± 2 (biopsy 1) and 39 ± 6 (biopsy 2) months post‐LT, respectively. RFP was defined as an increase in the fibrosis score ≥ 2 from biopsy 1 to biopsy 2 (a mean interval of 33 ± 6 months). The ability of parameters at biopsy 1 to predict RFP was compared with the areas under receiver operating characteristic curves (AUROCs). Of the 46 subjects, 15 developed RFP. Serum HA and YKL‐40 performed significantly better than conventional parameters and HSCA in predicting RFP post‐LT for HCV at biopsy 1, with AUROCs of 0.89 and 0.92, respectively. The accuracy of serum HA ≥ 90 μg/L and YKL‐40 ≥ 200 μg/L in predicting RFP at biopsy 1 was 80% and 96%, respectively. In conclusion, we found that elevated levels of serum HA and YKL‐40 within the first 6 months after LT accurately predicted RFP. Larger studies evaluating the role of serum HA and YKL‐40 in post‐LT management are warranted. Liver Transpl 14:1294–1302, 2008.

Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (Hepatology 2015;62:1004‐1012)