Robert M. Coben

Gastroesophageal reflux during gastrostomy feeding

BACKGROUND/AIMS Aspiration pneumonia is one of the most serious complications of gastrostomy tube feeding, with a reported incidence of 10%-20% in nursing home patients. The aims of this prospective study were to examine lower esophageal sphincter (LES) pressure before and after placement of gastrostomy tubes and to examine the effects of rapid intragastric bolus and slow, continuous feeding on LES pressure. METHODS Ten subjects were enrolled in the study. Basal LES pressure was measured before and after placement of gastrostomy tubes. Thereafter, LES pressure was measured for 15 minutes during rapid intragastric infusion of 250 mL of an enteral feeding formula and 100 mL water and continuous infusion of the enteral feeding formula at 80 mL/h. Scintigrams evaluating gastroesophageal reflux were obtained during each method of feeding. RESULTS Placement of gastrostomy tubes had no effect on basal LES pressure. Rapid intragastric bolus infusion led to a reduction in LES pressure to incompetent levels at 2.1 +/- 2.0 mm Hg (P < 0.001). Free gastroesophageal reflux to the sternal notch was shown by scintigraphy. Slow, continuous gastrostomy feedings did not alter LES pressure (P > 0.05) or show free gastroesophageal reflux by scintigraphy. CONCLUSIONS Gastroesophageal reflux and aspiration in patients fed via the gastrostomy tube may be caused by LES relaxation secondary to gastric distention caused by distention of the stomach.

Targeted cyst wall puncture and aspiration during EUS-FNA increases the diagnostic yield of premalignant and malignant pancreatic cysts

BACKGROUND Characterization of pancreatic cysts by using EUS-FNA includes chemical and cytologic analysis. OBJECTIVE To evaluate whether material obtained from FNA of the cyst wall increases diagnostic yield. DESIGN Prospective series. SETTING Tertiary referral center. PATIENTS Consecutive patients with pancreatic cysts referred for EUS-FNA between March 2010 and March 2011. INTERVENTION FNA was performed with aspiration of cyst fluid for carcinoembryonic antigen (CEA) and cytology, followed by cyst wall puncture (CWP). CWP is defined as puncturing the far wall of the cyst and moving the needle back and forth through the wall to sample the wall epithelium. MAIN OUTCOME MEASUREMENTS The diagnostic yield for mucinous cystic pancreatic neoplasms by CEA and cytology obtained from cyst fluid compared with cytology obtained from CWP. CEA ≥192 ng/mL was considered mucinous. RESULTS A total of 69 pancreatic cysts from 66 patients were included. Adequate amounts of fluid were aspirated for CEA, amylase, and cytology in 60 cysts (81%). Cellular material adequate for cytologic assessment from CWP was obtained in 56 cysts (81%). Ten (30%) of 33 cysts with CEA <192 ng/mL and negative results of cyst fluid cytology had a mucinous diagnosis from CWP; 6 of 9 (67%) cysts with an insufficient amount of fluid for CEA analysis and cyst fluid cytology had a mucinous diagnosis from CWP. Furthermore, 4 malignant cysts were independently diagnosed by CWP cytology. The incremental diagnostic yield of CWP for mucinous or malignant cysts was therefore 29% (20 of 69 cysts, P = .0001). An episode of pancreatitis (1.45%) occurred. LIMITATION Lack of surgical criterion standard. CONCLUSIONS CWP during EUS-FNA is a safe and effective technique for improving the diagnostic yield for premalignant and malignant pancreatic cysts.

A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation.

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow‐up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46–66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20–73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha‐fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3–36 months) while that of the treated was 80 months (15–152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV‐associated HCC.

Prevention of new hepatocellular carcinoma with concomitant antiviral therapy in chronic hepatitis B patients whose initial tumor was successfully ablated

Dear Editor, One of the major goals of antiviral treatment for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Prospective and retrospective studies have demonstrated reduced HCC incidence in CHB patients with Lamivudine (LAM) therapy. In prospective study of 3,653 HBV carriers, the most important risk factor for HCC was HBV DNA levels. The incidence of HCC correlated with HBV DNA levels at entry and throughout the study period. We investigated whether antiviral therapy prevents new HCC in CHB patients who have already developed HCC. It is the standard of care to ablate tumor locally unless tumor is large or has metastasized. Local treatments include surgery, transarterial chemoembolization (TACE), percutaneous ethanol injection (PCEI), cryoablation or radiofrequency tumor ablation (RFA). In the majority of patients, however, even after successful interventional therapy, new, recurrent or metastatic tumor would occur and patients die of advanced HCC resulting from uncontrolled HBV infection. In recent years, several reports from Japan have shown improved survival with lamivudine (LAM) therapy in patients following local treatment of HCC. We report the effect of antiviral therapy on long-term survival (some patients approaching >10 years) of CHB patients whose initial HCC is locally ablated. This study was approved by the Institutional Review Board of Thomas Jefferson University. Diagnosis of HCC was made by magnetic resonance imaging (MRI), alphafetoprotein (AFP) or histology. The 1.5 Tesla contrast enhanced MR imaging was used to assess HCC. The MRI criteria for HCC included a mass demonstrating low to intermediate T1 signal on precontrast images, homogeneous, heterogeneous, or ring enhancement during the hepatic arterial phase and/or moderate hyperintensity on intermediate T2-weighted fat suppressed spin-echo images with washout relative to surrounding liver parenchyma on delayed post contrast images. Nodules that were hyperintense on T1weighted pulse sequences but did not demonstrate arterial phase enhancement or T2 hyperintensity were considered dysplastic. Fifteen CHB patients with a single HCC ( 4 cm, the size defined as locally curable) received local ablation and were judged to have a complete response to one of the following modalities; resection, cryoablation, TACE, RFA and PCEI. MRI was obtained 1 month after ablation and at 3 month intervals subsequently. All were HBs-Ag positive, anti-HCV negative and Asian Americans. None received antiviral therapy before HCC diagnosis. Six patients, diagnosed between 1991 and 1997 who received no antiviral therapy were considered the historical controls. Nine patients diagnosed between 2000 and 2004 received antiviral therapy immediately at diagnosis, initially with LAM later with tenofovir (TDF) which was available off-label in 2001, and with adefovir (ADV) in 2002. Decision to add ADV or TDF was based on LAM resistance defined by the virologic breakthrough. We examined patients’ clinical course and compared the survival between the treated and untreated. Table 1 compares two groups. Median age, size of HCC and AFP levels between the two are similar. Six untreated patients show a median survival of 12.5 months and nine treated a median survival of 60 months. Survival difference between the two is significant (p 1⁄4 0.006 by Mann-Whitney). Table 2 shows details of the untreated. Not shown in the table are the median bilirubin 1.1 mg/dL (0.9–2.0) and ALT 48 U/L (37–81). HBV DNA levels were measured at different times and by outside laboratories using different cut-off levels. Since Thomas Jefferson University Hospital is a tertiary center, patients usually had HBV DNA done before their first visit. Because this group was not on anti-HBV therapy, HBV DNA levels were not assayed at regular intervals during the follow up. All underwent local tumor ablation and were considered to have successful elimination. All six developed new tumor(s) at one or multiple sites. Five died within 17 months. One developed new HCC at 20 months and died of multiple HCC at 36 months. Table 3 shows nine treated patients. Not shown in the table are median bilirubin 0.8 mg/dL (0.4–1.1) and ALT 59 U/L (28–158). All received LAM, later with ADV or TDF in some. HBV DNA became undetectable in all nine patients at median 8 months (range 3–13 months). For those who brought the HBV DNA from outside, subsequent HBV DNA during therapy were assayed at Jefferson Hospital by a Le tt er to th e E di to r

A retrospective analysis of medical or surgical therapy in young patients with diverticulitis.

Background : Acute diverticulitis is increasingly being recognized in younger patients, but its management remains controversial.

Usefulness of Highly Sensitive AFP-L3 and DCP in Surveillance for Hepatocellular Carcinoma in Patients with a Normal Alpha-Fetoprotein

Background and aims: Early detection of Hepatocellular Carcinoma (HCC) is crucial for effective management. Incidence of HCC has increased in the United States largely attributed to hepatitis B and C virus. Lens culinaris agglutinin-reactive Alpha-Fetoprotein (AFP-L3) and Des-Gamma-Carboxy Prothrombin (DCP) are being recognized specific biomarkers for HCC. Methods: We measured AFP-L3 and DCP in serial serum specimens of a cohort of chronic hepatitis patients on HCC surveillance and compared these markers to abdominal imaging. Among fifty patients who developed HCC during surveillance, 30 were included in the study with available sera 1-2 years before, at diagnosis and post ablation of HCC. For controls, three consecutive annual sera were examined from 106 chronic hepatitis patients without HCC during surveillance for 5-10 years. The μTASWako i30 auto analyzer was used for the assay that utilizes the microfluidics chip based assay platform. It can fractionate AFP-L3 glycoform and calculates AFP-L3% if AFP level is ≥ 0.6 ng/mL. Results: Combination of AFP, AFP-L3 and DCP showed high sensitivity of 83% in all patients and 75% in patients with AFP<20 ng/mL. AFP-L3 and DCP assays were useful in patients with low levels of AFP (<20 ng/mL) and could detect significant AFP-L3% elevation in some patients more than one year before the diagnosis of HCC. Furthermore, AFP-L3 predicted recurrence of HCC. Conclusions: This is the first study in the U.S. patients using the μTASWako i30 analyzer to test these HCC biomarkers. Our results suggest that combinations of these biomarkers are highly useful for early detection of HCC.

Clinical outcomes of medical or surgical therapy in patients below age 40 with acute diverticulitis

Clinical outcomes of medical or surgical therapy in patients below age 40 with acute diverticulitis

Extensive abdominal aortitis in a patient with Crohn's disease.

A 36-year-old woman with past medical history of Crohns disease presented to our hospital with fever and back pain. Initial computed tomography (CT) demonstrated extensive abdominal aortitis. Here, we discuss the very rare association between Crohns disease and aortitis, in addition to clinical and radiographic follow-up for our patient.

Update Treatment for HBV Infection and Persistent Risk for Hepatocellular Carcinoma: Prospect for an HBV Cure

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC. These results were documented with lamivudine, entecavir, and tenofovir. Nonetheless, as the duration of antiviral treatment increases, the risk for HCC still remains despite undetectable HBV DNA in serum, as reported by different investigators with observation up to 4–5 years. In our own experience, we are witnessing the development of HCC in patients who have received antiviral treatment. Some have enjoyed negative serum HBV DNA for over 12 years before developing HCC. Current treatment with NAs can effectively suppress the replication of the virus but cannot eradicate the covalently closed circular DNA (cccDNA) that is within the nucleus of hepatocytes. There still remains a great need for a cure for HBV. Fortunately, several compounds have been identified that have the potential to eradicate HBV, and there are ongoing clinical trials in progress in their early stages.

Perceived utility and availability of endoscopic ultrasonography in the staging of esophageal cancers: a national survey of gastroenterologists

Purpose: Although endoscopic ultrasonography (EUS) is well recognized as a valuable tool for staging esophageal cancer, its utilization in practice is inconsistent. The purpose of this study is to evaluate the perceived value of EUS in staging esophageal cancer and to determine the actual utilization of EUS.