Percutaneous Direct Needle Puncture and Transcatheter N-butyl Cyanoacrylate Injection Techniques for the Embolization of Pseudoaneurysms and Aneurysms of Arteries Supplying the Hepato-pancreato-biliary System and Gastrointestinal Tract.

AIMS: The aim of this study was to evaluate the safety and clinical efficacy of percutaneous direct needle puncture and transcatheter N-butyl cyanoacrylate (NBCA) injection techniques for the embolization of pseudoaneurysms and aneurysms of arteries supplying the hepato-pancreato-biliary (HPB) system and gastrointestinal (GI) tract. SUBJECTS AND METHODS: A hospital-based cross-sectional retrospective study was conducted, where the study group comprised 11 patients with pseudoaneurysms/aneurysms of arteries supplying the HPB system and GI tract presenting to a tertiary care center from January 2015 to June 2016. Four patients (36.4%) underwent percutaneous direct needle puncture of pseudoaneurysms with NBCA injection, 3 patients (27.3%) underwent transcatheter embolization with NBCA as sole embolic agent, and in 4 patients (36.4%), transcatheter NBCA injection was done along with coil embolization. RESULTS: This retrospective study comprised 11 patients (8 males and 3 females) with mean age of 35.8 years ± 1.6 (standard deviation [SD]). The mean volume of NBCA: ethiodized oil (lipiodol) mixture injected by percutaneous direct needle puncture was 0.62 ml ± 0.25 (SD) (range = 0.5-1 ml), and by transcatheter injection, it was 0.62 ml ± 0.37 (SD) (range = 0.3-1.4 ml). Embolization with NBCA was technically and clinically successful in all patients (100%). No recurrence of bleeding or recurrence of pseudoaneurysm/aneurysm was noted in our study. CONCLUSIONS: Percutaneous direct needle puncture of visceral artery pseudoaneurysms and NBCA glue injection and transcatheter NBCA injection for embolization of visceral artery pseudoaneurysms and aneurysms are cost-effective techniques that can be used when coil embolization is not feasible or has failed.

Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy.

We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 -1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 -1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 -592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 -1082A/G and CC genotype of IL-10 -592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

Brain MR imaging and 1H-MR spectroscopy changes in patients with extrahepatic portal vein obstruction from early childhood to adulthood.

BACKGROUND AND PURPOSE: MR imaging and (1)H-MR spectroscopy changes are well reported in cirrhotic patients, whereas they are inadequately reported in EHPVO. The aim of this study was to investigate age-related changes in brain MR imaging and metabolite profile in EHPVO with and without MHE and to explore any correlation of imaging and (1)H-MR spectroscopy parameters with blood ammonia. MATERIALS AND METHODS: Sixty-three patients with EHPVO (children, 7-12 years [n = 22], adolescents, 13-18 years [n = 15] and adults, 19-41 years [n = 26]) and 47 healthy age/sex-matched volunteers were studied. Neuropsychological tests, MR imaging, (1)H-MR spectroscopy, and blood ammonia estimation were performed in all subjects. RESULTS: Of 63 EHPVO patients, 25 (40%) who had MHE showed significantly increased MD, Glx, and blood ammonia in all 3 age groups; however, myo-inositol was significantly lower only in adults when compared with controls. MD positively correlated with blood ammonia and Glx in all age groups. Brain choline levels were normal in all patients with different age groups. CONCLUSIONS: Increases in brain MD, Glx, and blood ammonia were associated with MHE in all age groups. Normal brain choline in EHPVO signifies healthy liver and may serve as a diagnostic marker for its differentiation from cirrhosis-induced encephalopathy. Significant decrease of myo-inositol in adults is probably due to cellular osmoregulation secondary to long-standing hyperammonemia.

Gastroduodenal dysmotility in patients with gallbladder carcinoma: frequency of occurrence and clinical importance.

BACKGROUND: Gastric stasis, common in patients with gall-bladder carcinoma (GBC), results from anatomical obstruction or motor abnormalities. We studied patients with GBC for antroduodenal motor dysfunction using manometry. METHODS: Forty-one patients with GBC without endoscopic gastric outlet obstruction and 10 healthy controls were evaluated using a symptom scoring system for gastric stasis, saline load test and water perfusion antroduodenal manometry. Fasting, post-prandial and post-octreotide motility were recorded and analysed on a computer using GiPC manometry software. RESULTS: Sixteen of 41 patients (39%) with GBC reported recurrent vomiting; patients with vomiting had a higher symptom score (13 [11-17] v. 6 [4-10], p<0.0001] and higher volume of aspirate on the saline load test (460 ml [210-650] v. 160 ml [70-260], p<0.0001) as compared with those without vomiting. Healthy subjects more often had spontaneous fasting migratory motor complex than patients with GBC (9/10 v. 13/41, p=0.002). The amplitudes of contractions in the antrum and duodenum were significantly lower in patients with GBC than in healthy subjects. Patients with GBC had lower fasting (157 [68-284] v. 190.5 [150-284], p=0.01) and post-prandial (200 [96-395] v. 284 [178-395], p<0.0001) antral motor indices than healthy subjects. Patients with GBC and vomiting had significantly lower contraction amplitude and motility indices than those without vomiting. Motility indices correlated inversely with the symptom score and volume of aspirate on the saline load test (Spearman correlation, p = 0.01 for all). CONCLUSION: Antroduodenal motor abnormalities are common in patients with GBC. These may explain the symptoms of gastric stasis and abnormal results of the saline load test in the absence of anatomical obstruction in such patients.

Long-term follow-up after pneumatic dilation for achalasia cardia: factors associated with treatment failure and recurrence.

BACKGROUND: Though most patients with achalasia cardia (AC) respond to pneumatic dilation (PD), one-third experienced recurrence. Long-term follow-up studies on factors associated with various outcomes are scanty. METHODS: In this retrospective study, 126 patients (36.5 +/- 14.6 yr, 76 male) with AC (diagnosed by esophagoscopy, barium esophagogram, and/or manometry) were followed up in person or through mail. The median dysphagia-free duration was calculated by Kaplan-Meier analysis. Factors associated with nonresponse and recurrence after PD were determined using univariate and multivariate analyses. RESULTS: Symptoms were dysphagia (126, 100%), chest pain (21, 17%), regurgitation (61, 48%), weight loss (33, 26%), and pulmonary symptoms (23, 18%); 5 of 126 (4%) had megaesophagus (> or =7 cm). The mean lower esophageal sphincter (LES) pressure was 38.7 +/- 16.8 mmHg. One hundred and fifteen of 126 (91%) patients responded to PD (90 (71%) to first session); 25 of these had recurrence of dysphagia after 15 +/- 17 months. Post-PD chest pain requiring hospitalization occurred in 21 of 126 (17%; one had an esophageal perforation). Post-PD LES pressure, which was assessed in 48 of 126 patients, had decreased by >50% from baseline in 14 of 29 responders, 0 of 11 nonresponders (p= 0.004, chi(2) test), and 5 of 8 relapsers. The median dysphagia-free duration by Kaplan-Meier analysis was 60 months (SE 2.7, 95% CI 54.7-65.3). On univariate analysis, male gender, pulmonary symptoms (nocturnal coughing spell, history of respiratory infection), absence of chest pain, and failure to achieve a reduction in LES pressure >50% after PD were associated with poor outcome; whereas age, grade of dysphagia, regurgitation, megaesophagus, and LES pressure before PD were not. Male gender was associated with poor outcome by multivariate-analysis. CONCLUSIONS: PD is an effective and safe treatment for AC. Post-PD LES pressure measurement may be helpful in assessing response. Male patients have poorer outcomes following PD.

Correlation of esophageal pH and motor abnormalities with endoscopic severity of reflux esophagitis.

Motility abnormalities, common in gastroesophageal reflux disease, are likely to be related to endoscopic esophagitis. We studied pH and manometry parameters in relation to the severity of esophagitis. Forty-seven patients with symptomatic gastroesophageal reflux disease for > 3 months were evaluated by: (i) endoscopy (grading of esophagitis by Savary-Miller classification); (ii) mucosal biopsy; (iii) manometry; and (iv) 24-h pH-metry. We found Savary-Miller's grades of: 0 (9 patients out of 47), I (16/47), II (16/47), III (4/47), IV (2/47). Distal esophageal contraction amplitude was lower in severe (grade II to IV) as compared with mild (grade 0 and I) esophagitis (49 [7-182] versus 83 [27-196] mmHg [P = 0.001]). The length and pressure in the lower esophageal sphincter (LES), duration and velocity of contraction in the body, number of episodes of reflux and long-duration reflux, longest reflux, median pH, per cent of time with pH < 4 and DeMeester scores were not significantly different between the two groups. The area under pH 4 showed a negative correlation with LES pressure and amplitude of distal esophageal contractions. We conclude that higher endoscopic grades of esophagitis are associated with lower amplitude of contraction in distal esophagus. Lower LES pressure and distal esophageal contraction amplitude are associated with greater area under curve for pH below 4.

Minimal hepatic encephalopathy: natural history, impact on daily functioning, and role of treatment.

Cirrhosis of liver is often complicated by minimal hepatic encephalopathy (mHE), which is detected by neuropsychiatric and neurophysiological tests. mHE develops more commonly in cirrhotics with severe liver disease and in those with esophageal and gastric varices. On follow up, these patients more often develop overt encephalopathy as compared to cirrhotics without mHE. mHE may affect daily activities like sleep, driving ability, alertness, social interaction, and communication. It is probably also an independent predictor of survival. The most practical treatment strategy for mHE has not been established; however, it can be treated as effectively as overt encephalopathy with similar agents. Treatment improves mHE in terms of psychometric tests, but improvement in daily functioning has not been well documented.

Autoimmune liver disease in children.

BACKGROUND AND AIM: Autoimmune liver disease (AILD) in children progresses to cirrhosis and liver failure if not diagnosed and managed in time. We prospectively analyzed our patients with liver disease for autoimmune etiology and their outcome with treatment. METHODS: All patients with liver disease were evaluated with liver function tests, abdominal ultrasonography, endoscopy, liver biopsy, viral markers and investigations for Wilson's disease. Immunoglobin (Ig)M hepatitis A virus, hepatitis E virus (HEV) and IgM hepatitis B core antibody were tested if acute viral hepatitis was suspected. Antinuclear antibody (ANA), antismooth muscle antibody (SMA), and liver kidney microsomal antibody (anti-LKM-1) were done in all cases. Autoimmune liver disease was diagnosed when one or more autoantibodies tested positive (> 1:40), and no other etiology of liver disease was identified. We also applied criteria proposed by the International Autoimmune Hepatitis Group. Cases diagnosed to have AILD were treated with immunosuppressive drugs. RESULTS: Autoimmune liver disease constituted 3.9% (6/153; median age and duration of illness 8.5 years and 3 months, respectively) of chronic liver disease cases. Four patients had acute hepatitis-like presentation. Of the six cases, two each were ANA and SMA +; one was anti-LKM-1 +, and the other was positive for both SMA and anti-LKM-1. Three of the patients achieved remission with combination therapy of oral prednisolone (OP) and azathioprine (AZT), and one with only OP. The other two patients were not treated. Two of the patients in remission have been weaned off from immunosuppressive therapy, and one is in a withdrawal phase. Another patient, while in biochemical remission developed superimposed anicteric acute HEV infection. CONCLUSION: Although AILD is uncommon in children, its search is rewarding, as remission is achieved with immunosuppressive therapy. Superimposed acute viral hepatitis can occur in endemic areas.

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis.

BACKGROUND AND AIMS: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. METHODS: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. RESULTS: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of

Role of Helicobacter pylori infection in hyperammonemia and subclinical hepatic encephalopathy in cirrhosis of liver.

INTRODUCTION: Gastric Helicobacter pylori infection is believed to be associated with a higher risk of hepatic encephalopathy among patients with cirrhosis of liver. However, the role of this infection in causation of subclinical hepatic encephalopathy has not been studied in detail. METHODS: Patients with cirrhosis of liver but no hepatic encephalopathy underwent venous blood ammonia measurement, psychometric tests (number connection tests [NCT] and figure connection tests [FCT]), and gastric biopsies for presence of H. pylori infection. The results of blood ammonia and psychometric tests in the H. pylori-positive and -negative study subjects were compared. RESULTS: Of 58 patients with liver cirrhosis studied, 31 had evidence of gastric H. pylori infection. Venous blood ammonia levels were comparable in patients with (median 29 mmol/L; range 18-47) and without (34 [15-48] mmol/L; p=ns) H. pylori infection. The time taken to complete NCT trail A (median 37 s [range 25-69] versus 36.5 [26-62]), NCT trail B (64 s [48-91] versus 63.5 [42-88]), FCT trail A (59 s [31-115] versus 58 [38-590]) and FCT trail B (76 s [55-187] versus 82 [36-125]) were similar in those with and those without H. pylori infection. For each of the four tests, the proportion of subjects with abnormal test results was similar among H. pylori-positive and -negative subjects. CONCLUSION: Presence of H. pylori infection among patients with cirrhosis of liver but no overt hepatic encephalopathy is not associated with increase in blood ammonia concentration or deterioration in psychomotor function.

Symptomatic chronic calcific pancreatitis in a patient with idiopathic ulcerative colitis and sclerosing cholangitis.

Although sclerosing cholangitis is well recognized to occur in patients with idiopathic inflammatory bowel disease, pancreatitis as a complication of ulcerative colitis is uncommon. We describe a patient who had idiopathic ulcerative colitis, primary sclerosing cholangitis and calcific pancreatitis with endocrine pancreatic deficiency, a rare combination.

Gastrointestinal endoscopy training in India.

A structured endoscopy training program with clear goals for proper teaching and evaluation serves to alleviate apprehensions in the minds of trainees regarding this crucial area. It also ensures that training is acquired not in isolation but in the setting of ongoing patient care, so that the emphasis is on how the procedure fits into the overall management plan for the patient. By specifying the details of the endoscopy unit set-up, the qualifications of the trainer and the number of procedures to be performed by the trainee, it is hoped that uniformity will be produced in the quality of training imparted, whether it be in a teaching or a non-teaching hospital. The end-product of such training, through the DM/MCh or the DNB stream, is a gastroenterologist who is also a certified endoscopist, capable of performing all standard diagnostic and therapeutic procedures. A further period of focused training for 1 to 2 years is required to achieve the level of competence expected of an advanced therapeutic endoscopist. There is little room for short-term training courses in endoscopy for the basic training of an endoscopist, although such courses are useful as CME activities, for the maintenance and renewal of skills of the trained endoscopist, as well as providing him with exposure to new and evolving therapeutic techniques. Efforts at improving and standardizing the training and practice of GI endoscopy in India are likely to remain exercises in futility without the active and dynamic involvement of all the leading professional societies in the country. The need of the hour is the establishment of technical committees for laying down standards in training and practice of GI endoscopy that should be voluntarily approved by all these societies so that they may then be implemented by the State medical councils and the MCI. A move in this direction from within the profession is far more appropriate and is also likely to find greater acceptance than such moves imposed from above, at the behest of judicial authorities. A system of hospital accreditation committees for large public and private sector hospitals offering endoscopy services, supervised by the accreditation committee of the State medical council, needs to be established. Clinics and nursing homes offering these services also need to be approved by the same committee after meeting standards similar to those laid down for larger hospitals. Mechanisms for audits of performance and outcome of endoscopic procedures as well as periodic participation in CME activities for maintenance of skills and expertise need to be established and linked to periodic renewal of credentials for practising GI endoscopy. Procedures for credentialing for new endoscopic techniques need to be established. The path ahead is long and arduous but we must tread it for it will only become more difficult if we procrastinate.

Endosonographic, endoscopic, and histologic evaluation of alterations in the rectal venous system in patients with portal hypertension.

BACKGROUND: Colorectal varices and congestive rectopathy or colopathy have been erratically reported in patients with portal hypertension. The clinical importance of these entities has not been described. We assessed the changes in the venous system of the rectum by endoscopy and rectal endosonography (EUS). We also assessed the role of factors such as etiology of portal hypertension, grade of esophageal varices, sclerotherapy, and liver disease severity on the occurrence of these vascular changes. METHODS: We studied changes in the venous system of the rectum using endoscopy and EUS in 60 patients with portal hypertension (cirrhotic 41, noncirrhotic 19). Ten patients with irritable bowel syndrome and 6 patients with hemorrhoids served as controls. Rectal varices were classified as tortuous, nodular, and tumorous. Corresponding appearances on rectal EUS were classified as single or discrete multiple, multiple, and innumerable submucosal veins, respectively. Evidence of congestive rectopathy was also recorded. RESULTS: Prevalence of rectal varices was 43.3% on endoscopy (73% tortuous, 19% nodular, and 8% tumorous) and 75% on EUS (p < 0.0005). The latter showed corresponding appearances of submucosal veins in 25 of 26 patients and detected submucosal veins not identified at endoscopy in 19 other patients. Congestive rectopathy was found in 38.3% of patients. Multiple small dilated vessels in the submucosa were seen in 23.3% patients on rectal EUS. The development of these vascular changes was significantly influenced by sclerotherapy, but not by higher grade of esophageal varices, the etiology of portal hypertension, or severity of liver disease. CONCLUSIONS: Changes in the rectal venous system are common, with rectal EUS being superior to endoscopy in detecting early, as well as florid, changes.

Oesophageal motility and gastro-oesophageal reflux: effect of variceal eradication by endoscopic sclerotherapy.

Endoscopic injection sclerotherapy (EIS) is known to produce oesophageal structural and motility changes; however, alterations in frequency and severity of gastro-oesophageal reflux (GER) following EIS have not been investigated in detail. We studied 22 patients with cirrhosis and oesophageal varices before EIS and 26 after variceal eradication with intravariceal EIS using manometry and 24 h pH monitoring. The post-EIS group had reduced oesophageal sphincter pressure (19.2+/-11.4 vs 26.1 +/-16.4 mmHg, P< 0.05) and slower velocity of oesophageal peristalsis (2.47+/-0.71 vs 3.06+/-0.77 cm/s, P< 0.01) than the pre-EIS patients. There was no difference in the amplitude or duration of the contraction. Abnormal contraction wave-forms were observed more frequently in post-EIS than in the pre-EIS patients (3/22 vs 12/26, P< 0.05). Various quantitative parameters for GER were not increased in post-EIS compared with pre-EIS patients. Abnormal GER was present in nine of 21 pre-EIS and eight of 17 post-EIS patients (no significant difference). These results suggest that although persistent oesophageal motility changes are frequent after intravariceal EIS, these do not lead to a significant increase in GER.

Biliary ascariasis complicating endoscopic sphincterotomy for choledocholithiasis in India.

Endoscopic sphincterotomy is the treatment of choice for patients with choledocholithiasis. Biliary ascariasis has been reported from many parts of the world but is common in Kashmir, India. We report five cases of biliary ascariasis of which four were the result of post-endoscopic sphincterotomy for choledocholithiasis. Therefore, biliary ascariasis is not an uncommon complication of endoscopic sphincterotomy.

Spontaneous passage of gallbladder calculi--facilitation by endoscopic sphincterotomy.

After endoscopic sphincterotopy (ES) gallbladder motility increases leading to expulsion of crystals and stones. But this is not a universal phenomenon. We evaluated cholangiographic findings in patients emptying their gallbladder after ES for common bile duct (CBD) stones. Cholangiographic features of twenty patients expelling gallbladder calculi after ES were studied. Controls included 20 age and sex matched patients with gallstones and CBD stones, who did not expel gallstones after ES. Of 20 cases in study group, 9 recovered more than 20 stones each in the stool within 7 days of ES. Repeat ERCP showed empty gallbladder in all, whereas CBD was full of stones in 11 of the 20 cases. In the study group, low insertion of the cystic duct was more common (10 vs 0, p < 0.04), the cystic duct made a narrow angle (20 +/- 5 degrees vs 50 +/- 10 degrees, p < 0.04) with CBD before insertion and cystic duct diameter was higher (5 mm vs 2.5 mm, p < 0.04) as compared to controls. We conclude that in patients undergoing ES with intact gallbladder and small gallbladder calculi, spontaneous emptying of gallbladder calculi occurs, if cystic duct is wider, has low insertion and makes narrow angle with CBD before insertion.

Biliary stenting for management of common bile duct stones.

Large and multiple common bile duct stones may defy extraction despite an adequate endoscopic papillotomy. We treated 65 patients with symptomatic bile duct stones with endoscopic stents after failed attempts at stone extraction. Of the 65 patients, bile duct stones were extracted in eight at a second attempt, 29 underwent elective surgery and 28 patients were followed with the stent in situ for 21-52 months (median 42 months). During follow up, two patients had recurrent pain and two required surgery. The remaining 24 patients remained asymptomatic. Biliary stenting is a safe and effective mode of treatment for common bile duct stones in patients who have failed stone extraction after endoscopic papillotomy.

Bile lithogenicity and gallbladder emptying in patients with microlithiasis: effect of bile acid therapy.

BACKGROUND & AIMS: Biliary cholesterol supersaturation, rapid nucleation of cholesterol, and altered gallbladder motility are prerequisite for gallstone formation. However, the pathogenesis of microlithiasis is not clear. The aim of this study was to determine the abnormalities of gallbladder emptying and bile composition in patients with microlithiasis. METHODS: Nucleation time, cholesterol saturation index (CSI), and gallbladder emptying were studied in patients with microlithiasis (n = 10), patients with gallstones (n = 10), and healthy volunteers (n = 10). Bile analysis was repeated in 6 patients with microlithiasis treated with ursodeoxycholic acid (UDCA) for 8 weeks. RESULTS: Nucleation time was shorter in patients with microlithiasis and those with gallstones than in healthy volunteers (P < 0.0001). Patients with microlithiasis had longer nucleation time than those with gallstones (P < 0.001). There was no difference in cholesterol levels and CSI in gallstone and microlithiasis patients. However, healthy volunteers had lower cholesterol levels (P < 0.01) and CSI (P < 0.01). Patients with microlithiasis had prolongation of nucleation time (P < 0.001) and lowering of CSI (P < 0.001) after UDCA therapy. Gallbladder ejection fraction was higher in microlithiasis patients than in gallstone patients (P < 0.01) but lower than in healthy volunteers (P < 0.01). CONCLUSIONS: Patients with microlithiasis have longer nucleation time and better gallbladder emptying than patients with gallstones. Bile abnormalities can be successfully corrected with UDCA therapy in patients with microlithiasis.