Sandborn WJ, Regula J, Feagan BG, et al.Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis. Gastroenterology 2009;137:1934-43.
Drugs that deliver 5-aminosalicylate as the active moiety are effective as first-line therapy for induction and maintenance treatment in patients with mild and moder-ately active ulcerative colitis (UC). However, the optimal induction dose of mesalamine in this setting is unclear. This multicenter, randomized, double-blind, 6-week (ASCEND III) was conducted at 113 sites in 14 coun-tries in Europe and America to determine the efficacy and safety of delayed release mesalamine 4.8 g/day compared with 2.4 g/day in patients with moderately active UC. The primary endpoint was treatment success at week 6, defined as improvement in the Physician’s Global Assessment (PGA), with no worsening in any individual clinical assessment in the intention to treat population. Compo-nents of the PGA scoring system included stool frequency, rectal bleeding, and sigmoidoscopy with contact friability test (CFT) assessments.
Seven hundred and seventy-two eligible patients were randomized (in a 1:1 ratio) and assessed at scree
ning and weeks 0 (baseline), 3, and 6. PGA score was used for assessment of disease severity and efficacy.For the primary endpoint, 4.8 g/d of mesalamine was noninferior  to 2.4 g/d. 70% patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% receiving 2.4 g/day (p=ns). Significantly more patients who received 4.8 g/day achieved clinical remission at week 3 (p=0.02) and week 6 (43% of patients on 4.8 g/day vs. 35% on 2.4 g/day, p=0.04).
Rates of improvement for individual assessments, including stool frequency, rectal bleeding, endoscopic improvement and PGA (week 6 only) were similar in the two groups. Treatment success at week 6 in favor of 4.8 g/day was consistent among most subgroups. Subgroup analyses demonstrated an advantage for 4.8 g/day in patients previously treated with corticosteroids (p=0.05), oral mesalamine (p=0.07), rectal therapies (p=0.06), or multiple UC medications (p=0.01).
The authors conclude that delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC. Linn FH, Houwen RH, van Hattum J, van der Kleij S, van Erpecum KJ. Long-term exclusive zinc monotherapy in symptomatic Wilson disease: experience in 17 patients. Hepatology 2009;50:1442-52.
The optimal medical therapy in symptomatic Wilson’s disease is controversial. D-penicillamine is reco
mmended initially, but side effects can require discontinuation in up to 30% of cases and neurologic deterioration may occur in many patients. Zinc is often used as the initial monotherapy in asymptomatic patients, and in symptomatic patients as maintenance treatment after D-penicillamine. There are no data on symptomatic patients treated exclusively with zinc.
Seventeen symptomatic patients with Wilson’s disease were treated with zinc monotherapy and followed for median 14 years. Zinc was initially prescribed as sulfate (dose 135 mg elemental zinc/day), and later modified based on clinical symptoms and signs, serum non–ceruloplas-min-bound copper concentrations (aim: <10 µg/dL), and urinary copper excretions (aim: <100 µg/24 hours) during follow-up.
The mean age at diagnosis and start of treatment was 18 years. Presentation was exclusively hepatic, exclusively neurologic, and combined in 7, 5 and 5 patients, respec-tively. Liver disease severity at baseline was classified as mild, moderate, compensated endstage liver disease (ESLD) or decompensated ESLD. At baseline 2/12 patients with hepatic disease had decompensated ESLD, 5 had com-pensated ESLD, and 5 had mild disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of 5 patients with initial com-pensated ESLD progressed to decompensated state, and 2 remained stable. Three of 5 patients with moderate
or mild liver disease remain stable and 2 improved. A decreasing bilirubin level was seen during follow up. Nine of 10 neu-rologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neu-rologic symptoms. The efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. Side effects were infrequent.
The authors conclude that zinc can be a first-line option for some individuals, especially for neurologi-cally impaired patients with stable liver disease. A lesscharacterise
Indian J Gastroenterol 2009(November–December):28(6):228–230 Gastroenterology Elsewhere
satisfactory outcome in hepatic disease may relate to less efficient decoppering.
Ignjatovic A, East JE, Suzuki N, Vance M, Guenther T, Saunders BP. Optical diagnosis of small colorectal polyps at routine colonoscopy (Detect InSpect ChAracterise Resect and Discard; DISCARD trial): a prospective cohort study.Lancet Oncol 2009;10:1171-8.
Most polyps detected at colonoscopy are small (6–9 mm) or diminutive (≤5 mm). Almost 50% of all small polyps are non-neoplastic and many polypectomies are unnecessary and expose patients to add
ed risks. Accurate optical diagnosis of small colorectal polyps in vivo, would allow hyperplastic polyps to be left in situ and small adenomas to be resected and discarded without a need for pathologic examination. Conventional white-light colonoscopy is not accurate in differentiating neoplastic from non-neoplastic polyps. Narrow-band imaging (NBI) enhances mucosal and vascular detail and is an option for optical diagnosis.
DISCARD was a prospective, cohort study of 130 con-secutive patients with positive fecal occult blood test or with previous adenomas undergoing surveillance. It aimed to assess whether optical diagnosis of small polyps is feasible and safe in routine clinical practice. Four colonoscopists used optical diagnosis with high-definition white light, fol-lowed by NBI without magnification and chromoendoscopy using 0·1% indigo carmine to predict polyp histology. The primary outcome was accuracy of polyp characterization using optical diagnosis compared with histopathology.
Three hundred and sixty-three small/diminutive polyps were detected, of which 278 polyps had both optical and histopathological diagnosis. On pathology, 198 were ade-nomas and 80 were non-neoplastic lesions (62 hyperplastic polyps, 15 normal mucosa, 3 serrated lesions without dys-plasia). Optical diagnosis correctly diagnosed 186/198 adenomas (sensitivity 0.94; 95% CI 0.90-0.97) and 55/62 hyperplastic polyps (specificity 0.89; 0.78-0.95), with an overall accuracy of 241/260 (0.93, 0.89-
0.96) for polyp characterization. Optical diagnosis was incorrect in 19 polyps; 12 adenomas were endoscopically diagnosed as hyperplastic polyps and 7 hyperplastic polyps were pre-dicted to be adenomas.Expert colonoscopists were more accurate than nonexperts in optical diagnosis of adenomas (96%vs 88%; p=0·04) and had better overall accuracy (95% vs 87%, p=0·03).
The authors conclude that for small/ diminutive polyps, optical diagnosis using high-definition white light and non-magnified NBI seems to be an acceptable and cost effective strategy to assess polyp histopathology.
Compiled by Prachi Patil,
Tata Memorial Hospital, Mumbai
Gastroenterology India
Tandan M, Reddy DN, Santosh D, Reddy V, Koppuju V, Lakhtakia S, et al. Extracorporeal shock wave lithotripsy of large difficult common bile duct stones: Efficacy and analysis of factors that favor stone fragmentation. J Gastroenterol Hepatol 2009;24:1370–4.
Only about 10% of large CBD stones (size >15 mm) can be extracted by routine endoscopic technique
s. This pro-spective study assesses the efficacy of extracorporeal shock wave lithotripsy (ESWL) on fragmentation of large CBD stones.
Two hundred and thirty-eight patients (age 18–86 years; under epidural anesthesia - 254 patients [89.8%], general anesthesia - 29; nasobiliary tube - 279, T-tube - 4) underwent ESWL. ESWL was done with a 3rd generation lithotripter, which had both bidimensional fluoroscopy and ultrasound targeting facilities. ESWL was initiated at a setting of 1 (11,000 kV) and increased to 4–5 (14,000–15,000 kV) over 5–7 min, frequency of 90 shocks/min and maximum 5000 shocks per session. Fragmentation was considered satisfactory when the calculi were broken down to < 5 mm diameter. ERCP was done within 48 h after ESWL for the clearance of the fragments. ESWL was considered unsuc-cessful if fragmentation of the calculi was not initiated after 4 sessions.
Single calculus was seen in 130 (45.9%) patients. Most (276 [97.5%]) calculi were radiolucent and the mean greatest diameter was 3.2 (1.8 – 7) cm. Fragmentation was achieved in a single session in 46 patients; 101 required 2 sessions, 64 needed 3 sessions, and 77 needed 4 or more sessions. Complete clearance of CBD was seen in 239 patients (84.5%). Partial fragmentation with clearance of the CBD >50% of the stone volume was seen in 35 (12.4%) and the procedure was unsuccessful in 9 patients; of these, 14 underwent surgery, 17 refused surgery and opted for repeated stenting and 13 w
ere lost to follow-up. A total of 784 sessions were required for 283 patients (mean 2.7). The range of shock waves delivered was between 4200 and 33,780 (mean 13,890). Single radio opaque calculi needed a mean of 9500 shocks (range 8800 to 10,280) while radio-lucent calculi received 5900 shocks (4600 to 7300). ESWL without saline irrigation needed 25,000 shocks (24,100 to 25,900) for fragmentation as compared to 12,100 shocks
(11,300 to 13,100) for ESWL with saline irrigation. The time taken for each session of ESWL was between 75 and 90 min. Thirty-four patients had mild hemobilia, 11 had cholangitis, 10 had mild post ERCP pancreatitis and 21% had purpuric spots on the skin after ESWL. Epidural anes-thesia, shock frequency of 90/min, radiolucent calculi and presence of fluid around the calculus helped in better frag-mentation.
This study shows that ESWL is an efficacious nonin-vasive therapeutic modality for difficult CBD stones with low complication rate. It is ‘curative’ in post cholecys-tectomy CBD stones as well as in patients with isolated CBD calculi and effective in intrahepatic lithiasis.
Wig JD, Bharathy KGS, Kochhar R, et al. Correlates of organ failure in severe acute pancreatitis. J Pancreas 2009; 10:271-5.
One hundred and sixty-one patients (124 men; mean age - 41.5 years; alcohol - 72, gallstones - 56) with severe acute pancreatitis (SAP) were evaluated. SAP was diagnosed if the patient had organ failure according to the Atlanta cri-teria, necrosis on CT scan or an APACHE II score > 7. At CT scan 41 of 157 (26.1%) had < 30% necrosis, 50 had 30-50% necrosis while 66 had > 50% necrosis. Eighty-four (52.2%) patients had organ failure; 41 had single organ failure. Pulmonary failure was the commonest (n=64), fol-lowed by renal (50) and cardiovascular failure (28). The mean APACHE score was 9.4 (4.5) and CT severity index was ≥7 in 115 (73.2%) patients. Patients with multiorgan failure were older (p=0.007). The mean APACHE II score was 8.0 in those without organ failure, 10.2 in those with single organ failure, and 17.2 in those with 3 organ failure; the incidence of multiorgan failure increased with increasing APACHE score (p<0.001). Pancreatic necrosis on CT scan in patients with one, two and three organ failures was 48.8%, 51.8% and 83.3%, respectively while, in patients without organ failure, 28.6% had >50% necrosis (p<0.001). Sixty-six patients had culture-proven infective necrosis. No relationship was found between the presence of infective necrosis and occurrence of organ failure. Eighty-four (52.2%) patients were managed conservatively while 77 (47.8%) underwent surgical necrosectomy. Seventy-seven patients died, 60/84 with organ failure and 17/77 without organ failure (71.4%vs. 22.1%; p<0.001). There was a sig-nificant correlation between the number of organ failures and mortality, with a mortality rate of 58.5% (24/41) in those with 1 organ failure, 75.0% (21/28) in those with 2 organ failures and 100% (15/15) in those with 3 organ failures (p<0.001).
This study concludes that organ failure occurs in about 52% of patients with SAP. The occurrence of organ failure correlated with an increase in age, higher APACHE II score and extent of pancreatic necrosis and not with infected necrosis. Overall mortality was about 48% and this corre-lated with the number of organs failing.
Jha SK, Kumar A, Sharma BC, Sarin SK. Systemic and pulmonary hemodynamics in patients with extrahe-patic portal vein obstruction is similar to compensated cirrhotic patients.Hepatol Int 2009;3:384–91.
Patients with cirrhosis and portal hypertension (PH) have a hyperdynamic circulation with increased cardiac output, heart rate and plasma volume; and decreased arterial blood pressure, systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR). These changes are related to both hepatocellular dysfunction. The role of PH in producing these changes in circulation is not clear. Extra-hepatic portal vein obstruction (EHPVO) is an excellent model to study the role of PH alone in producing these changes because there is no hepatic dysfunction in EHPVO. This prospective study evaluated the role of PH per se on systemic and pulmonary hemodynamics in patients with EHPVO.
Fifteen EHPVO patients with past variceal bleeding and 15  controls (compensated cirrhosis with histor
y of variceal bleed; matched by variceal status and body surface) underwent hemodynamic studies which included the mea-surements of hepatic venous pressure gradient (HVPG), right atrial pressure (RAP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), and mean arterial pressure (MAP). Cardiac output was calculated by Fick’s oxygen method. The median (range) HVPG in EHPVO and compensated cirrhosis patients was 3 (2–10) and 14 (9–26) mmHg, respectively (p<0.01). Both EHPVO patients and cirrhotic patients had similar values in all the measured hemodynamic parameters. The cardiac index (EHPVO 3.8 [2.3–7.7] l min-L m-2, cir-rhosis 4.4 [2.8–8.9] L min-1m-2) and systemic vascular resistance index (EHPVO 1,835 [806–3400] dyne s cm-5 m-2, cirrhosis 1,800 [668–3022]) and PVR index (EHPVO 71 [42–332] vs. cirrhosis 79 [18–428]) were comparable in the two groups.
The results demonstrate that EHPVO has features of hyperdynamic circulation with increased cardiac index and decreased systemic and PVRI. These changes are similar to those seen in patients with cirrhosis. This suggests a pre-dominant role of portal hypertension per se in the genesis of systemic and pulmonary hemodynamic alterations.
Compiled by Sundeep Shah, Mumbai

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