Metabolic pancreatitis: Etiopathogenesis and management.

Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study.

BACKGROUND AND AIM: The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

The diagnostic accuracy and strength of agreement between endoscopic ultrasound and histopathology in the staging of ampullary tumors.

AIM: Ampullary tumors are rare. Reports on ampullary tumor staging are heterogeneous and combine both periampullary and ampullary tumors. This study assessed the performance of endoscopic ultrasound (EUS) in the local staging of ampullary tumors only. METHODS: Data were collected retrospectively. We included patients with an ampullary tumor who underwent EUS and surgical resection. Tumor (T) and nodal (N) TNM staging for EUS and histopathological (HP) staging were compared. RESULTS: From 2009 to 2010, a total of 79 patients with ampullary tumors were identified. Of these, 26 had both EUS and Whipple's surgery and were included (28 did not undergo resection, 13 had palliative surgery only and 12 had resection without EUS). For T staging by HP, there were 2 (7.7 %) T1, 11 (42.3 %) T2, 12 (46.2 %) T3 and 1 (3.8 %) T4 tumors. The accuracy of EUS T staging was 73.1 % with a Kappa value of 0.564 (p < 0.0001). The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) of EUS, respectively were 50.0 %, 91.7 %, 33.3 % and 95.7 % for T1 tumors; 81.8 %, 80.0 %, 75.0 % and 85.7 % for T2; 75.0 %, 92.9 %, 90.0 % and 81.3 % for T3 tumors. For N staging by HP, 17 (65.4 %) were N0 and 9 (34.6 %) N1. The N staging diagnostic accuracy was 80.8 % with a Kappa value of 0.586 (p = 0.003). The sensitivity, specificity, PPV, NPV for N0 disease were 82.4 %, 77.8 %, 87.5 % and 70.0 %, respectively while for N1 they were 77.8 %, 82.4 %, 70.0 % and 87.5 %, respectively. CONCLUSIONS: EUS had a moderate strength of agreement with histopathology for both T and N staging, and a high diagnostic accuracy for nodal staging.

HER2 expression in gastric cancer in Indian population--an immunohistochemistry and fluorescence in situ hybridization study.

AIM: Human epidermal growth factor receptor (HER2, also known neu, ERBB2) protein expression in gastric cancer is associated with poor prognosis, aggressive disease and poor response to chemotherapy. Trastuzumab, a monoclonal antibody against HER2, in combination with chemotherapy is currently advocated as a new standard option for patients with HER2-positive advanced gastric and gastroesophageal junction carcinoma. Frequency of HER2 expression in gastric cancer has been reported from different geographic zones with a wide range of 13 % to 91 %. There are no reported data of HER2 protein expression in gastric cancer tissue from India. The purpose of this study was to evaluate the frequency of HER2 expression in gastric cancer. METHODS: The frequency of HER2 expression in 52 patients with gastric adenocarcinoma was prospectively evaluated over a six month period at Asian Institute of Gastroenterology from January 2010 to July 2010, using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS: HER2 overexpression was confirmed in 23 of 52 (44.2 %) patients. Two patients had equivocal result by IHC (2+), one of whom was positive on analysis by FISH. There was no difference in HER2 overexpression (positivity) or negativity in relation to age, gender, tumor site, histological subtype, tumor differentiation, serosal involvement or lymph nodal status. HER2 overexpression rates were similar for intestinal type as compared to diffuse histological type (OR 1.84), as also for proximal as compared to distal gastric cancers (OR 0.81). CONCLUSION: HER2 overexpression was observed in significant number of advanced gastric adenocarcinoma patients. There was no difference in HER2 overexpression in relation to clinicopathological parameters.

Endoscopic ultrasound guided fine-needle aspiration of lymph nodes and solid masses: factors influencing the cellularity and adequacy of the aspirate.

GOALS: To study the factors that influence the cellularity and adequacy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). BACKGROUND: An on-site cytopathology service is preferred during EUS-guided FNA. However, this is not always available. Factors that influence the aspirate cellularity and adequacy have not been well defined in the absence of on-site cytopathology. STUDY: EUS-guided FNA procedures without an on-site cytopathologist from a single center were retrospectively studied. FNA of solid masses and lymph nodes (LN) were included. The FNA cellularity, hemorrhagic content, and endoscopists' assessment of adequacy were analyzed. RESULTS: A total of 166 patients from January 2009 to October 2010 were included. A total of 520 FNA passes were performed. Of the 166 lesions, 70 (42.2%) were solid masses and 96 (57.8%) were LNs. A 22-G needle was used in 72.3% and 25 G in 27.7% of the patients. The median (range) number of FNA passes was 3 (1 to 7) for LNs and 3 (1 to 5) for solid masses. With this, the endoscopists had an accuracy of 92.2% (153/166) for obtaining an adequate aspirate. Of the 166 samples, 4 (2.4%) were acellular, 20 (12.0%) sparsely cellular, 52 (31.4%) moderately cellular, and 90 (54.2%) highly cellular. The 25-G needle had significantly more adequate aspirates than the 22-G needle for solid masses (P=0.011). Also, increasing passes correlated with higher cellularity (P=0.002) and an adequate aspirate (P=0.021). No correlation was found for LN FNA. Lesion size did not influence the cellularity or adequacy (P>0.05). The degree of hemorrhage was not influenced by the needle gauge, number of passes, or lesion size. The diagnostic yield was not affected by hemorrhage in the sample (P>0.05). CONCLUSIONS: EUS-guided FNA obtains a high proportion of adequate aspirates for LNs and solid masses, even without an on-site cytopathologist. Small proportions of inadequate samples still occur. For solid masses, a 25-G needle with at least 3 passes is more likely to provide an adequate aspirate than a 22-G needle and fewer passes. Hemorrhage did not affect the cytopathology's ability to make a diagnosis.

Achalasia cardia with esophageal varix managed with endoscopic ultrasound-guided botulinum toxin injection.

Achalasia cardia is a motility disorder of the esophagus characterized by failure of relaxation of the lower esophageal sphincter. Nitrates and calcium channel blockers, pneumatic dilatation, botulinum toxin injection and surgical myotomy have been described in literature as possible management options. We present a patient who presented with achalasia and was co-incidentally diagnosed to have cryptogenic cirrhosis with portal hypertension and had esophageal varices. This clinical combination precluded the use of pneumatic dilatation and surgical myotomy. We injected botulinum toxin into the lower esophageal sphincter using a celiac plexus neurolysis needle under endoscopic ultrasound guidance; the clinical response was good.

Current status on the diagnosis and management of pancreatic cysts in the Asia-Pacific region: role of endoscopic ultrasound.

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Role of single-operator peroral cholangioscopy in the diagnosis of indeterminate biliary lesions: a single-center, prospective study.

BACKGROUND: Currently available techniques to diagnose indeterminate biliary lesions have many limitations. OBJECTIVE: To assess the accuracy of single-operator peroral cholangioscopy by using the SpyGlass system to differentiate malignant from benign disease in patients with indeterminate biliary lesions. DESIGN: Prospective, single-arm, single-center study. SETTING: Tertiary referral center. PATIENTS: Thirty-six patients with indeterminate biliary strictures and filling defects who had inconclusive results on previous biliary ductal tissue sampling. INTERVENTIONS: SpyGlass cholangioscopy with cholangioscopically guided intraductal biopsies. MAIN OUTCOME MEASUREMENTS: Accuracy of SpyGlass visual impression and SpyBite biopsies for differentiating malignant from benign ductal lesions. RESULTS: Thirty-six patients (22 men, mean age 48.3 years [range 27-68 years]) with indeterminate stricture and/or filling defects underwent SpyGlass cholangioscopy. Of the 22 patients with a final diagnosis of malignant lesion, cholangioscopic impression was malignant in 21 patients (95%) and benign in 1 patient (5%). Of the 14 patients with a final diagnosis of benign disease, including the 3 patients with common bile duct stones and no stricture, cholangioscopic impression was malignant in 3 patients (21%) and benign in 11 patients (79%). The overall accuracy of SpyGlass visual impression for differentiating malignant from benign ductal lesions was 89% (32/36). The accuracy of SpyBite biopsies for differentiating malignant from benign ductal lesions that were inconclusive on ERCP-guided brushing or biopsy was 82% (27/33) in an intent-to-treat analysis. LIMITATIONS: No randomized comparison with alternative diagnostic modalities for the nature of biliary strictures. CONCLUSIONS: SpyGlass cholangioscopy with SpyBite biopsies has a high accuracy with regard to confirming or excluding malignancy in patients with indeterminate biliary lesions.

Achalasia cardia subtyping by high-resolution manometry predicts the therapeutic outcome of pneumatic balloon dilatation.

BACKGROUND/AIMS: High-resolution manometry (HRM) with pressure topography is used to subtype achalasia cardia, which has therapeutic implications. The aim of this study was to compare the clinical characteristics, manometric variables and treatment outcomes among the achalasia subtypes based on the HRM findings. METHODS: The patients who underwent HRM at the Asian Institute of Gastroenterology, Hyderabad between January 2008 and January 2009 were enrolled. The patients with achalasia were categorized into 3 subtypes: type I - achalasia with minimum esophageal pressurization, type II - achalasia with esophageal compression and type III - achalasia with spasm. The clinical and manometric variables and treatment outcomes were compared. RESULTS: Eighty-nine out of the 900 patients who underwent HRM were diagnosed as achalasia cardia. Fifty-one patients with a minimum follow-up period of 6 months were included. Types I and II achalasia were diagnosed in 24 patients each and 3 patients were diagnosed as type III achalasia. Dysphagia and regurgitation were the main presenting symptoms in patients with types I and II achalasia. Patients with type III achalasia had high basal lower esophageal sphincter pressure and maximal esophageal pressurization when compared to types I and II. Most patients underwent pneumatic dilatation (type I, 22/24; type II, 20/24; type III, 3/3). Patients with type II had the best response to pneumatic dilatation (18/20, 90.0%) compared to types I (14/22, 63.3%) and III (1/3, 33.3%). CONCLUSIONS: The type II achalasia cardia showed the best response to pneumatic dilatation.

Granulocytic Sarcoma of the Stomach Presenting as Dysphagia during Pregnancy.

Granulocytic sarcoma also known as extramedullary myeloid sarcoma or chloroma is an uncommon manifestation of leukemia and presents as a deposit of leukemic cells outside the bone marrow. We report a case of a twenty-five-year-old pregnant woman who presented with progressive dysphagia and recurrent postprandial vomiting. Upper GI endoscopy had shown large flat laterally spread nodular lesions in the cardia and proximal body of stomach. Biopsies from the gastric lesion showed granulocytic sarcoma of the stomach. Concurrent peripheral and bone marrow picture was suggestive of acute myeloid leukemia (AML-M4). There is limited reported literature on granulocytic sarcoma of the stomach. Concurrent gastric granulocytic sarcoma involving cardia and AML in pregnancy has not been reported till date.

Epidural anesthesia is effective for extracorporeal shock wave lithotripsy of pancreatic and biliary calculi.

AIM: To evaluate the efficacy of thoracic epidural analgesia for extracorporeal shock wave lithotripsy (ESWL). METHODS: ESWL is an effective, non-invasive technique for the treatment of difficult pancreatic and large bile duct calculi. The procedure is often painful and requires large doses of analgesics. Many different anesthetic techniques have been used. Patients with either large bile duct calculi or pancreatic duct calculi which could not be extracted by routine endoscopic methods were selected. Thoracic epidural anesthesia (TEA) was routinely used in all the subjects unless contraindicated. Bupivacaine 0.25% with or without clonidine was used to block the segments D6 to D12. The dose was calculated depending on the age, height and weight of the patient. It was usually 1-2 mL per segment blocked. RESULTS: Ninety eight percent of the 1509 patients underwent ESWL under TEA. The subjects selected were within American Society of Anesthesiologists grade I to III. ESWL using EA permitted successful elimination of bile duct or pancreatic calculi with minimal morbidity. The procedure time was shorter in patients with TEA than in those who underwent ESWL under total intravenous anesthesia. CONCLUSION: Almost all patients undergoing ESWL with EA had effective blocks with a single catheter insertion and local anesthetic injection.

Spiral enteroscopy: a preliminary experience in Asian population.

BACKGROUND AND AIM: In spite of recent developments in the field of enteroscopy the small bowel remains the challenging organ to access. The spiral enteroscopy is a novel technique using a special over-tube (Endo-Ease Discovery SB) system for deep intubation of the small bowel. The aim of the present study was to evaluate the efficacy of spiral enteroscopy with an Olympus enteroscope (SIF Q 180) in an Asian subset of patients. METHODS: Between January and March 2010, 11 patients underwent spiral enteroscopies. The indication for the procedure was obscure gastrointestinal bleeding in five patients, Crohn's disease in two, malabsorbtion syndrome in two, Peutz-Jeghers syndrome in one and Osler Weber Rendu disease in one patient. RESULTS: Eleven patients (five male and six female) mean age 41.6 years (range 21-62 years) underwent spiral enteroscopy. Spiral enteroscopy advancement was successful in all patients. The average depth of insertion was 249 cm (range 120-400 cm) past the ligament of Treitz, and the average time for the procedure was 27.8 min (range 20-32 min). The findings included ulcers (n = 3), polyps (n = 1), arteriovenous malformation (n = 2), ulcer with stricture (n = 1), and lymphangiectasia (n = 1). No major complications were observed. CONCLUSION: In conclusion, our initial experience with spiral enteroscopy shows that it is easy to perform, takes less time than balloon assisted enteroscopy and is relatively safe.

Extracorporeal shock wave lithotripsy and endotherapy for pancreatic calculi-a large single center experience.

AIM: Large pancreatic ductal calculi and pain are a feature of chronic calcific pancreatitis (CCP) in the tropics. This large single center study evaluates the role of extracorporeal shock wave lithotripsy (ESWL) in fragmentation of large pancreatic stones and relief of pain in patients with CCP. METHODS: Patients with CCP presenting with pain and large pancreatic duct (PD) calculi (>5 mm diameter) not amenable to extraction at routine endoscopic retrograde cholangio pancreatography (ERCP) were taken up for ESWL using a 3rd generation lithotripter. Stones in the head and body of pancreas were targeted at ESWL; 5,000 shocks were given per session. The calculi were fragmented to <3 mm size and then cleared by endotherapy. Pancreatic duct stents were deployed when indicated. A total of 1,006 patients underwent ESWL. Complete clearance was achieved in 762 (76%), partial clearance in 173 (17%) and unsuccessful in the rest. More than 962 (90%) of patients needed less than three sessions of ESWL. At 6 months, 711 (84%) of 846 patients who returned for follow up had significant relief of pain with a decrease in analgesic use. Complications were mild and minimal. CONCLUSION: ESWL is an effective and safe modality for fragmentation of large PD calculi in patients with CCP.

Narrow band imaging cholangioscopy in hilar cholangiocarcinoma.

Per oral cholangioscopy has been developed as a diagnostic modality for evaluation of bile duct lesions. Per oral cholangioscope with narrow band imaging (NBI) system can provide good quality images of bile duct lesions. There is limited data on per oral cholangioscopy using NBI in biliary tract diseases. We report our experience of NBI cholangioscopy in hilar strictures.

Diagnostic yield and therapeutic impact of single-balloon enteroscopy: series of 106 cases.

BACKGROUND AND AIM: Single-balloon enteroscopy (SBE) is a novel method of balloon assisted enteroscopy which allows deep intubation of intestine and has therapeutic potential. This prospective study was done in a tertiary care center to evaluate the feasibility, complications, diagnostic and therapeutic yield of SBE in patients with suspected small bowel disorders. METHODS: One hundred and six patients (mean age 40.1 years, range 12-76 years, 65 men) with suspected small bowel diseases underwent 131 SBE procedures between February 2007 and July 2008. RESULTS: Indications for SBE included obscure gastrointestinal bleeding (OGIB) (40), chronic abdominal pain with abnormal imaging studies (34), chronic diarrhea (20), polyposis syndromes (11) and foreign body (1).The mean insertion depth was 255.8 +/- 84.5 cm beyond the duodenojejunal flexure by the oral route and 163 +/- 59.3 cm proximal to the ileocecal valve by the per anal approach. The mean duration of the procedure for antegrade and retrograde enteroscopy was 65.9 +/- 19.5 min and 72.3 +/- 18.3 min, respectively. Pan-enteroscopy was possible in 25% of cases (five of 20 cases in which total enteroscopy was attempted). Diagnostic yields in cases of OGIB, chronic abdominal pain and chronic diarrhea were 60%, 65% and 55%, respectively. Overall new diagnosis was established in 46% and the extent of known disease was assessed in 15% of cases. In 21% of patients, therapeutic interventions were carried out while surgical treatment was directed to 8.4% of the patients. No major complications were observed. CONCLUSION: SBE is well tolerated and has good diagnostic yield, having a similar yield to previous double-balloon enteroscopy reports.

Extracorporeal shock wave lithotripsy of large difficult common bile duct stones: efficacy and analysis of factors that favor stone fragmentation.

BACKGROUND AND AIM: Difficult common bile duct stones (CBD) are those not amenable to extraction by the standard technique of sphincterotomy followed by use of a Dormia basket or balloon. The role of extracorporeal shock wave lithotripsy (ESWL) in stone fragmentation and clearance of difficult CBD stones and the factors which favor fragmentation were prospectively evaluated in the present study. METHODS: A total of 283 patients with large CBD stones were subjected to ESWL. A maximum of 5000 shocks was delivered per session until CBD stones were fragmented to less than 5 mm diameter. CBD was cleared by biliary endotherapy using a basket or balloon. Outcome was assessed by CBD clearance. RESULTS: Total CBD clearance was achieved in 239 patients (84.4%) and partial CBD clearance in 35 patients (12.3%). Three or fewer sessions of ESWL were required in 74.6% of patients. Minor complications were seen in 45 patients (15.9%). There was no procedure-related mortality. Epidural anesthesia, shock frequency of 90/min, radiolucent calculi and presence of fluid around the calculus helped in better fragmentation. CONCLUSION: A high success rate, negligible complications and non-invasive nature of the procedure make ESWL a useful tool for removing large CBD stones.