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Asif Khalid

Publications and source records attributed to Asif Khalid.

15 recordsLinked to original sources
PubMed2007

EUS yield in evaluating biliary dilatation in patients with normal serum liver enzymes.

The finding of common bile duct (CBD) dilatation on abdominal imaging frequently results in additional testing. It has been our impression that endoscopic ultrasound (EUS) evaluation of a dilated CBD is a low-yield examination in the setting of normal serum liver enzymes. We therefore sought to evaluate the EUS yield in evaluating CBD dilatation in patients with normal as compared to elevated serum liver enzymes. A retrospective review was performed to identify patients referred for EUS evaluation of a dilated CBD in the absence of obvious pathology on prior imaging. Charts were reviewed for patient symptoms, presence of elevated serum liver enzymes, imaging studies before EUS, and EUS findings. Exclusion criteria included clinical jaundice, known biliary stricture, mass lesion or stone, and previously sphincterotomy and/or stent placement. Forty-seven patients were identified: 32 with normal and 15 with elevated serum liver enzymes. There was no difference in mean CBD diameter between these two groups (8.51 vs. 8.79 mm, p=0.854). Of the entire group, 15 patients had undergone prior magnetic resonance cholangiopancreatography (MRCP); an additional 7 patients had undergone prior endoscopic retrograde cholangiopancreatography (ERCP). EUS findings to explain CBD dilatation were found more commonly in patients with elevated compared with normal serum liver enzymes (53% vs. 6%, p=0.001). Periampullary diverticula and choledocholithiasis were the most common findings; of 32 patients with normal serum liver enzymes, one periampullary diverticulum and one CBD stone were found, respectively. The CBD stone had been missed by prior MRCP examination. Of 15 patients with elevated serum liver enzymes, there were 3 cases of choledocholithiasis, 4 periampullary diverticula, and 1 ampullary tumor. EUS should be the test of choice for further evaluation of CBD dilatation when index imaging is normal. Although the EUS yield is low in cases of biliary dilatation in the setting of normal serum liver enzymes, its preferential use would potentially avoid unnecessary MRCP and ERCP.

Adult↗
PubMed2006

Endoscopic ultrasound-guided fine needle aspirate microsatellite loss analysis and pancreatic endocrine tumor outcome.

BACKGROUND & AIMS: The clinical course of pancreatic endocrine tumor (PET) varies depending on tumor aggressiveness, disease extent, and possibly accumulated molecular alterations. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) results, although accurate in diagnosing PET, correlate poorly with PET outcome. The role of detecting key molecular abnormalities in predicting PET behavior and clinical outcome from EUS-FNA material remains unknown. METHODS: Patients with confirmed PET who underwent EUS-FNA during a 32-month period were included. Patient demographics and clinical data were recorded and follow-up information was obtained by contacting their physician to evaluate disease progression. Representative tumor cells were microdissected from the FNA material. DNA was harvested and amplified, targeting a panel of 17 polymorphic microsatellite markers on chromosomes 1p, 3p, 5q, 9p, 10q, 11q, 17p, 17q, 21q, and 22q. The polymerase chain reaction products were subjected to fluorescent capillary gel electrophoresis to detect microsatellite loss. The fractional allelic loss (FAL) was calculated. RESULTS: Twenty-five patients were studied. Thirteen were classified histologically as benign PET limited to the pancreas and 12 as malignant PET (invasive or metastatic). The mean FAL in the benign and malignant PET was 0.03 and 0.37 (P<.0001), respectively. In addition, the mean FAL was significantly greater in those with disease progression as compared with patients with stable disease (0.45 vs 0.09 respectively, P<.0001). CONCLUSIONS: Microsatellite loss analysis of EUS-FNA material from PET can be performed reliably and an FAL value of more than 0.2 is associated with disease progression. This technique may have value in the preoperative assessment and risk stratification of patients with PET.

Adult↗
PubMed2006

Detection of unsuspected left hepatic lobe metastases during EUS staging of cancer of the esophagus and cardia.

BACKGROUND: High resolution imaging of the left hepatic lobe can be obtained via endoscopic ultrasound (EUS), allowing for detection of unsuspected metastatic disease during cancer staging. The frequency at which occult liver metastases are detected during EUS staging of cancer of the esophagus and cardia is unknown. METHODS: Over an 18-month period, 98 patients underwent EUS staging for a new diagnosis of cancer of the esophagus and cardia. Wire-guided dilation was performed if necessary. Standard radial examination was followed by curvilinear evaluation with attention to the left hepatic lobe. All suspicious liver lesions were aspirated under EUS guidance. RESULTS: The radial and curvilinear echoendoscope were successfully passed to the antrum in 86% and 81% of cases, respectively, without complication. Thirty-two percent of patients required dilation. Lesions suspicious for left hepatic lobe metastases were found in 7% of cases that could be completely evaluated by EUS, all of which underwent EUS-guided fine needle aspiration. All lesions were proven metastases: four true-positive and one false-negative cytologic result. CONCLUSION: Curvilinear EUS examination of the left hepatic lobe in addition to standard radial EUS examination can be performed safely when staging cancer of the esophagus and cardia. Dedicated left hepatic lobe examination should be performed as it avoids unnecessary surgery in a subset of these patients by detection of occult liver metastases.

Adenocarcinoma↗
PubMed2006

EUS-guided paracentesis for the diagnosis of malignant ascites.

BACKGROUND: EUS and EUS-guided fine-needle aspiration (EUS-FNA) have well-defined roles in the diagnosis and staging of GI and pancreaticobiliary malignancy. Malignant ascites usually represents peritoneal carcinomatosis, increases disease stage, and portends a poor prognosis. There are limited data regarding the yield of EUS-guided paracentesis (EUS-P) for the diagnosis of malignant ascites. OBJECTIVE: To determine the usefulness of EUS-P for the diagnosis of malignant ascites. DESIGN: Prospective case series. SETTING: Tertiary referral academic center. PATIENTS: Those presenting for EUS examination for suspected or proven malignancy over a 16-month period were evaluated prospectively for the presence of ascites. INTERVENTIONS: EUS-P was performed via a transgastric or transduodenal approach if ascites was detected. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, and negative predictive value of EUS-P for diagnosing malignant ascites. RESULTS: Six hundred twenty-nine patients were studied. Twenty-five patients with ascites who met inclusion criteria comprised the study cohort. The mean volume of ascites aspirated was 6.8 mL (range, 1-20 mL). Sixty-four percent (16 of 25) of EUS-P samples revealed malignant cytology. Of the group with negative ascitic cytology, 67% (6 of 9) had a proven malignancy. There was one false-negative cytology result. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-P for diagnosing malignant ascites was 94%, 100%, 100%, and 89%, respectively. The complication rate was 4%; 1 patient developed bacterial peritonitis after EUS-P. LIMITATIONS: The study did not address cost savings in patient care based on the diagnosis of malignant ascites. CONCLUSIONS: EUS-P is highly sensitive and specific for diagnosing malignant ascites. The finding of malignant ascites significantly alters patient management, so an active search for ascites and use of EUS-P should be incorporated into the diagnosis and staging of upper GI and pancreaticobiliary malignancy.

Aged↗
PubMed2006

Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses.

OBJECTIVES: Accurate diagnosis of malignant and benign pancreatic masses can be challenging, potentially delaying treatment for cancer and subjecting patients with benign disease to unnecessary surgery. Endoscopic ultrasound fine needle aspirate (EUS-FNA) of pancreatic masses remains inconclusive in a subset of patients. The role of EUS-FNA molecular analysis in this context is studied. METHODS: Patients with benign pancreatic masses (6 cases, 4 autoimmune pancreatitis, 2 focal chronic pancreatitis) and malignant pancreatic masses (15) with inconclusive cytology (5 cases) and positive cytology (10 controls) were selected. All cases had definitive pathology. Representative cells were microdissected from each EUS-FNA sample and subjected to PCR for analysis of 16 microsatellite allele loss markers situated at 1p, 3p, 5q, 9p, 9q, 10q, 17p, 17q, 21q, and 22q. Loss of heterozygosity analysis used fluorescent capillary electrophoresis for quantitative determination of allelic imbalance. k-ras-2 point mutation analysis was also performed. Mean fractional mutation rate (FMR) was calculated and compared for each group. RESULTS: All malignant cases carried multiple mutations (FMR 0.50), regardless of positive cytology (FMR 0.52) or suspicious cytology (FMR 0.47) (p = NS). Five of the 6 benign cases carried no mutations whereas 1 case of autoimmune pancreatitis and coexisting PanIN lesions exhibited a k-ras mutation (FMR 0.01). The mean FMR for the malignant and benign samples was significantly different (p < 0.0001). CONCLUSIONS: Broad panel microsatellite loss and k-ras point mutation analysis can be reliably performed on EUS-FNA samples from pancreatic masses and improves the diagnostic accuracy. Furthermore, it accurately differentiates between malignant and benign pancreatic masses.

Adult↗
PubMed2005

Molecular diagnosis of solid and cystic lesions of the pancreas.

Pancreatic cancer presents at a clinically advanced stage. Diagnosis often is delayed in those who undergo several negative investigations, and at times, the diagnosis ultimately is made at surgery. Tumor suppressor-linked microsatellite allelic loss analysis appears to improve the diagnostic accuracy of inconclusive cytology specimens. Science, however, still suffers from the lack of a reliable biomarker for the purpose of screening and early detection. The continued study of sera and pancreatic juice hopefully will lead to the discovery of molecular biomarkers capable of diagnosing preclinical disease in at-risk groups.The ability to predict the underlying biologic behavior of pancreatic cystic neoplasia is less than ideal. Tumor suppressor-linked microsatellite allelic loss and telomerase analysis show promise, but they have not been studied extensively. Proteomic analysis of pancreatic cyst fluid, although not yet reported, also may prove valuable in guiding clinical management.

Genetic Markers↗
PubMed2005

The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology.

BACKGROUND & AIMS: Current methods to detect malignancy in mucinous cystic neoplasms of the pancreas remain inadequate. The role of detailed molecular analysis in this context was investigated. METHODS: Endoscopic ultrasound-guided pancreatic cyst aspirates were prospectively collected during a period of 19 months and studied for cytology, carcinoembryonic antigen level, and molecular analysis. Molecular evaluation incorporated DNA quantification (amount and quality), k-ras point mutation, and broad panel tumor suppressor linked microsatellite marker allelic loss analysis by using fluorescent capillary electrophoresis. The sequence of mutation acquisition was also calculated on the basis of a clonal expansion model, and comparison was made to the final pathology. RESULTS: Thirty-six cysts with confirmed histology were analyzed. There were 11 malignant, 15 premalignant, and 10 benign cysts. Malignant cysts could be differentiated from premalignant cysts on the basis of fluid carcinoembryonic antigen level (P=.034), DNA quality (P=.009), number of mutations (P=.002), and on the sequence of mutations acquired (P<.001). Early k-ras mutation followed by allelic loss was the most predictive of a malignant cyst (sensitivity, 91%; specificity, 93%). CONCLUSIONS: Malignant cyst fluid contains adequate DNA to allow mutational analysis. A first hit k-ras mutation followed by allelic loss is most predictive of the presence of malignancy in a pancreatic cyst. This approach should serve as an ancillary tool to the conventional work-up of pancreatic cysts. Cumulative amount and timing of detectable mutational damage can assist in diagnosis and clinical management.

Carcinoembryonic Antigen↗
PubMed2004

Molecular diagnosis of solid and cystic lesions of the pancreas.

Pancreatic cancer presents at a clinically advanced stage. Diagnosis often is delayed in those who undergo several negative investigations, and at times, the diagnosis ultimately is made at surgery. Tumor suppressor-linked microsatellite allelic loss analysis appears to improve the diagnostic accuracy of inconclusive cytology specimens. Science, however, still suffers from the lack of a reliable biomarker for the purpose of screening and early detection. The continued study of sera and pancreatic juice hopefully will lead to the discovery of molecular biomarkers capable of diagnosing pre-clinical disease in at-risk groups. The ability to predict the underlying biologic behavior of pancreatic cystic neoplasia is less than ideal. Tumor suppressor-linked microsatellite allelic loss and telomerase analysis show promise, but they have not been studied extensively. Proteomic analysis of pancreatic cyst fluid, although not yet reported, also may prove valuable in guiding clinical management.

Biomarkers↗
PubMed2003

Approach to idiopathic recurrent pancreatitis.

Acute pancreatitis is caused by acute or chronic alcohol intake or choledocholithiasis in approximately 80% of cases. In the absence of alcohol abuse or gallstones, a variety of established and putative factors must be considered, any of which can cause a single or recurrent attacks of acute pancreatitis. When the underlying cause eludes detection following an initial thorough search and leads to a second attack, the term idiopathic acute recurrent pancreatitis (IARP) is applied. This article discusses IARP and its work-up.

Acute Disease↗
PubMed2003

Secretin-stimulated magnetic resonance pancreaticogram to assess pancreatic duct outflow obstruction in evaluation of idiopathic acute recurrent pancreatitis: a pilot study.

Magnetic resonance pancreatography is a new modality to visualize the pancreatic duct. Prolonged dilation of the pancreatic duct following secretin administration may suggest obstruction at the level of the pancreatic duct orifice. We describe 10 patients with idiopathic acute recurrent pancreatitis who underwent secretin-stimulated magnetic resonance pancreatography with subsequent endoscopic retrograde pancreatogram with or without manometry. All patients had complete visualization of the main pancreatic duct and no evidence of chronic duct disease. Two patients had pancreas divisum. Three had prolonged dilation of the pancreatic duct on secretin-stimulated magnetic resonance pancreatography and evidence of pancreatic duct outflow obstruction. Four additional patients with pancreatic duct outflow obstruction had normal secretin-stimulated magnetic resonance pancreatography. In conclusion, secretin stimulated magnetic resonance pancreatography provides high quality pancreatic duct images and has high specificity but low sensitivity for diagnosing pancreatic duct outflow obstruction using manometric/clinical criteria.

Acute Disease↗
PubMed2002

Multiple loss of heterozygosity without K-ras mutation identified by molecular analysis on fine-needle aspiration cytology specimen of acinar cell carcinoma of pancreas.

Fine-needle aspiration diagnosis of pancreatic acinar cell carcinoma (PAC) is challenging. Typically, the cytologic findings in PAC are described as a cellular population of loosely cohesive clusters and single neoplastic cells. The individual cells have granular cytoplasm, uniform nuclei, a fine chromatin pattern, and occasional prominent nucleoli. These features are suggestive of PAC but not diagnostic. We illustrate a case in which the combination of cytopathologic findings, clinical information, and molecular analysis enabled us to arrive at the diagnosis of PAC. Although the cytomorphologic features alone were not specific, the presence of a markedly elevated serum lipase level, cutaneous lesions of fat necrosis, and loss of heterozygosity at 1p, 5q25 at the APC locus, 9p21 at the p16 locus, and 17p13 at the p53 locus were essential in excluding the main differential diagnostic entities including pancreatic ductal carcinoma, pancreatic endocrine tumor, and pancreatoblastoma.

Adenocarcinoma↗
PubMed2002

Conservative treatment of chronic pancreatitis.

Chronic pancreatitis has been difficult to treat because the origin, pathophysiologic mechanisms and causes of unrelenting pain are so poorly understood. Furthermore, the pharmacologic agents often employed in other diseases with pain appear to be ineffective in many cases. The conservative management of chronic pancreatitis aims at (1) limiting progression and complications of the disease; (2) replacing lost exocrine and endocrine function; and (3) pain control. Thus, life style changes such as cessation of alcohol consumption and tobacco smoking, trials of pancreatic enzymes, treatment of duct obstruction and pseudocysts, and surgical therapies are currently employed. The good news is that the understanding of the underlying pathophysiological mechanisms is now advancing rapidly, and hopefully patient-specific and highly effective therapies will become available in the near future.

Chronic Disease↗
PubMed2001

Pancreas Divisum.

We offer endoscopic therapy for pancreas divisum only in patients with acute recurrent pancreatitis or chronic pancreatitis, based on studies delineated in this article, which results in response rates of 80% and 50% respectively. We do not offer endoscopic therapy for patients with chronic abdominal pain in the absence of morphologic abnormalities in the pancreatic duct or parenchyma or normal laboratory study results. It has been our experience that the success rate for endoscopic cannulation and therapy directed at the minor papilla in patients with symptomatic pancreas divisum is improved when the procedure is performed with primary intent to treat in patients who have a pre-existing diagnosis of pancreas divisum, as opposed to patients who undergo diagnostic ERCP for idiopathic acute recurrent pancreatitis and are diagnosed with pancreas divisum during the procedure. We cannulate the minor papilla with ultratapered 3-F catheters and 0.018-in soft wires. It is our opinion that minor papilla sphincterotomy offers advantages over chronic stent therapy in treating patients with pancreas divisum. Although both techniques have proven efficacy, chronic stenting requires repeated procedures and results in a high incidence of stent-induced chronic duct changes, both of which can be avoided by performing a minor papillotomy. We use an ultratapered papillotome with a 20-mm monofilament cutting wire and typically use blended current. The papillotomy is extended to ablate the mucosal mound of the minor papilla typically in a 2-o'clock direction for a distance between 4 and 8 mm, depending on the patient's anatomy. Following minor papillotomy, we place temporary 5-F pancreatic duct stents to reduce the incidence of postprocedural pancreatitis, which has been demonstrated in pancreatic duct sphincterotomy of the major papilla. These stents usually migrate out after 24 to 72 hours following the procedure. We offer surgical sphincteroplasty to patients in whom minor papillotomy cannot be performed or whose disease relapses after successful endoscopic therapy.

Journal Article↗