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Biomedical subjects

William R Brugge

Publications and source records attributed to William R Brugge.

At least 19 recordsLinked to original sources
PubMed2006

EUS-guided injection of paclitaxel (OncoGel) provides therapeutic drug concentrations in the porcine pancreas (with video).

BACKGROUND: OncoGel (ReGel/paclitaxel) is an intralesional injectable formulation of the chemotherapeutic drug, paclitaxel, for local tumor management. OBJECTIVE: The aim of this study was to determine if a minimally invasive EUS-guided injection of paclitaxel, bound to a thermosensitive gel carrier, would lead to therapeutic tissue concentrations of the chemotherapeutic agent in the porcine pancreas. DESIGN: Eight Yorkshire breed pigs were sedated by general anesthesia and OncoGel was injected, under EUS-guidance, with a 22-gauge needle into the tail of the pancreas. MAIN OUTCOME MEASUREMENTS: During the 7-day (n = 4) or 14-day (n = 4) observational period, the animals were monitored by serum levels of amylase and lipase, and by a CT on day 4. The outcome was determined by gross and microscopic evidence of inflammation of the pancreas, clinical tolerance, and quantitation of tissue paclitaxel concentrations. RESULTS: Eight pigs underwent injection of 1, 2, 3, or 4 mL OncoGel (6 mg paclitaxel per 1 mL OncoGel) (n = 2 per group). An intrapancreatic hyperechoic focus, with an average diameter of 2.1 +/- 0.8 cm, was visible by EUS, and a hypodense area in the tail of the pancreas was visible by contrast CT. Clinically, the animals appeared to tolerate the procedure without sequelae. Blood levels of amylase and lipase were normal. At euthanasia, a depot of OncoGel, with an average diameter of 14.7 +/- 5.0 mm), was located both grossly and histologically in the pancreatic tail. After 14 days, clinically significant tissue concentrations of paclitaxel were detected at a distance of 30 to 50 mm from the depot in the animals that underwent an injection of 3 and 4 mL of the agent (n = 2). CONCLUSIONS: The EUS-guided injection of OncoGel into the pancreas of the pig provided high and sustained localized concentrations of paclitaxel. This technique is a potential minimally invasive local treatment option for unresectable pancreatic tumors.

Animals↗
PubMed2006

EUS staging of upper GI malignancies: results of a prospective randomized trial.

BACKGROUND: Electronic 270 degrees transverse-array EUS (TA-EUS) provides high-quality cross-sectional images but cannot guide FNA. Linear EUS (L-EUS) provides longitudinal images of malignancies and the ability to guide FNA. OBJECTIVE: We conducted a prospective randomized comparison of TA-EUS and L-EUS for the staging of upper-GI (UGI) malignancies. DESIGN: Forty-three patients underwent L-EUS immediately followed by TA-EUS (N = 27, 63%) or TA-EUS immediately followed by L-EUS (N = 16, 37%). PATIENTS: Forty-three subjects (mean age, 64 years; 37 men) with an UGI malignancy (4 stomach and 38 esophageal) were evaluated with both TA-EUS and L-EUS. INTERVENTIONS: Abnormal lymph nodes were sampled by FNA for cytology. RESULTS: There was agreement on the T stage by linear and radial techniques in 38 of 43 subjects (88%). Twenty-seven of 43 patients (63%) had abnormal lymph nodes by linear or transverse-array imaging. L-EUS demonstrated 66 abnormal lymph nodes in 27 subjects (average of 2.4 nodes/subject). TA-EUS demonstrated 90 abnormal lymph nodes in 27 subjects (average of 3.3 nodes/subject, P = .009, compared with L-EUS). In 16 of the 27 subjects, an FNA was performed, which was positive in 13 cases (81%) and negative in 3 cases (10%) for malignancy. CONCLUSIONS: TA-EUS and L-EUS provide similar results of T staging of UGI malignancies. However, the number of abnormal lymph nodes detected by TA-EUS was more than by L-EUS. These findings suggest that radial or transverse-array EUS imaging should be the primary method for staging of UGI malignancies.

Aged↗
PubMed2006

Intraductal papillary mucinous neoplasm of the pancreas: cytologic features predict histologic grade.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade. METHODS: Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis. RESULTS: The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002). CONCLUSIONS: The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.

Adenocarcinoma, Mucinous↗
PubMed2006

Pancreatic cysts 3 cm or smaller: how aggressive should treatment be?

PURPOSE: To retrospectively determine the frequency of malignancy in small (< or =3 cm) pancreatic cysts, to evaluate whether cyst morphologic features can help predict the presence of malignancy, and to determine the natural history of small pancreatic cysts at follow-up imaging. MATERIALS AND METHODS: Institutional review board approval was obtained; informed patient consent was not required. By means of a computerized search, 510 patients with pancreatic cysts that had been detected at computed tomography (CT) or magnetic resonance (MR) imaging were identified. Cysts that were 3 cm or smaller at surgery or endoscopic ultrasonography (US)-guided cyst fluid aspiration and biopsy were included. Eighty-six patients-31 men and 55 women aged 24-89 years-fulfilled the criteria. Patients underwent surgery or were monitored with endoscopic US-guided cyst fluid analysis, cytologic analysis, and follow-up imaging. Imaging findings were compared with surgical and pathology records and with endoscopic US features. Positive predictive values (PPVs) for benignity and malignancy were calculated on the basis of cyst size and absence or presence of septa in the cysts. RESULTS: Forty-eight patients underwent surgery, and 38 were treated nonsurgically. Seventy-five patients had benign cysts; eight, borderline (malignant) neoplasms; and three, carcinoma in situ lesions. The PPV of small pancreatic cysts for prediction of benignity was 87% (75 of 86 patients). Thirty-six patients had unilocular cysts (35 with benign lesions, one with borderline neoplasm). The PPV of unilocular cysts for prediction of benignity was 97% (35 of 36 patients). Fifty patients had septated cysts; seven of these patients had borderline neoplasms, and three had carcinoma in situ lesions. For prediction of malignancy in small cysts, the PPV of septa was 20% (10 of 50 patients), which was significantly higher than the 3% (one of 36 patients) PPV of unilocular cysts (P = .042). No significant changes in cyst morphologic features were seen in patients who were followed up with imaging for a mean period of 21.8 months. CONCLUSION: The majority (n = 75) of small pancreatic cysts were benign. Thirty-six cysts were unilocular, and virtually all of these (n = 35) were benign. The presence of septa was associated with borderline or in situ malignancy in 20% (10 of 50) of cases.

Adult↗
PubMed2006

Endoscopic mucosal resection using a cap-fitted endoscope improves tissue resection and pathology interpretation: an animal study.

BACKGROUND: Endoscopic mucosal resection using a cap-fitted endoscope (EMRC) has been proposed to be significantly better and safer for tissue resection compared with standard snare EMR. However, there are no valid animal or clinical data to support this. We aimed to compare EMRC with standard snare EMR in a porcine model with respect to tissue resected, ease of procedure, and degree of diathermic injury to the resected specimen. METHODS: Gastric EMRs were randomly performed in pigs using a variety of techniques, including EMRC (1mm and 17-mm cap) and the standard snare technique, using a single-channel method without a grasping forceps. Geometric and histological assessment of the resection specimen for size, histological depth, and diathermic injury were performed by a single pathologist, blinded to the endoscopic techniques used. RESULTS: Thirty-six gastric mucosal resections were randomly performed in three pigs. Use of EMRC resulted in a statistically significant greater resection specimen by weight, size, and histological depth compared with standard EMR (P < 0.04). Large-cap EMRC resulted in a statistically significant greater resection weight and size compared to small-cap EMRC (P < 0.05). There was a statistically significant greater degree of diathermic injury in the specimens resected using the standard snare EMR technique compared with EMRC (P < 0.006). There were no acute complications with either technique. CONCLUSION: Gastric EMRC is more technically effective than and as safe and easy as standard snare EMR. Use of the cap, especially the larger cap, is associated with larger and deeper mucosal resection and less diathermic injury compared with the standard snare technique, making the pathologic assessment of depth and margin involvement more reliable. When possible, EMRC should be the EMR method of choice.

Animals↗
PubMed2006

Endoscopic therapy of benign pyloric stenosis and gastric outlet obstruction.

PURPOSE OF REVIEW: To examine the short and long-term success rates of balloon dilation of pyloric stenosis. RECENT FINDINGS: Several large studies have demonstrated high rates of success for the relief of symptoms from pyloric stenosis using through-the-scope balloons. These dilating balloons readily increase the diameter of the stenotic pylorus on average from 6 to 16 mm. Patients who require more than two dilations are at high risk of endoscopic failure and the need for surgical intervention. Rapid re-stenosis rates are observed in patients with malignant pyloric obstruction. Since many patients with benign pyloric stenosis have underlying ulcer disease, helicobacter infection is a relatively common finding. Eradication of this infection at the time of balloon dilation will ensure higher long-term success rates. SUMMARY: In summary, benign pyloric stenosis can be readily treated with endoscopic balloon dilation and should be the first-line therapy.

Adult↗
PubMed2006

Endoscopic mucosal resection: an improved diagnostic procedure for early gastroesophageal epithelial neoplasms.

Endoscopic mucosal resection (EMR), which is advocated for the treatment of early (superficial) gastroesophageal neoplasms, has also been alluded to represent a superior diagnostic and staging modality. We compared the diagnostic concordance of preceding biopsies with EMR specimens in 31 gastric and 10 esophageal EMRs consisting of 6 low-grade and 12 high-grade dysplasias, 21 intramucosal adenocarcinomas, and 2 submucosal invasive adenocarcinomas. Discrepancies were considered as either major or minor if the histologic grades differed by 2 or more, or by only 1, respectively. Discrepant and concordant cases were compared with regard to the size of lesion (maximum dimension and surface area), number of biopsy fragments, and extent of biopsy sampling (ratio between lesion size and number of biopsy fragments). These same variables were used to evaluate the differences seen between gastric and esophageal cases. Of the 41 cases, 16 (39%) had discrepant diagnoses, including 14 gastric and 2 esophageal neoplasms. A major discrepancy was seen in 2% of the cases (n = 1, gastric) and a minor discrepancy, in 15 cases. All but 2 of the discrepant cases were found to have a higher grade on EMR. The average number of biopsy fragments was 4.4 in both concordant and discrepant groups. The maximal dimension, surface area, and biopsy sampling ratios of the lesion were significantly greater in the discrepant cases than in the concordant cases. The esophageal cases trended toward having smaller size and a significantly extensive biopsy sampling. We conclude that EMR is superior to biopsy for diagnosing superficial gastroesophageal tumors. Discrepancies between the specimens occur in larger lesions (>10 mm) with less extensive biopsy sampling. EMR can substantially modify the diagnostic grade of a lesion and therefore facilitate optimal therapeutic decisions by avoiding undertreatment and overtreatment based on inaccurate grading and staging.

Adenocarcinoma↗
PubMed2006

Autoimmune pancreatitis: a systemic immune complex mediated disease.

Autoimmune pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric disease. Recent reports of multiorgan inflammatory mass forming lesions with increased numbers of IgG4 positive plasma cells suggest that AIP may have a systemic component. In this study, we explore the systemic nature of AIP, investigate the relevance of subtyping AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and ultrastructurally evaluate the presence of immune complexes. Our study group consisted of 36 patients with AIP, 21 of whom underwent a Whipple procedure. On the basis of the pattern of inflammation, pancreatic involvement was subtyped as ductocentric (AIP-D) or lobulocentric (AIP-L). Extrapancreatic lesions included bile duct (n=3), salivary glands (n=3), lung (n=2), gallbladder (n=11), and kidney (n=4). Clinical and radiologic data was recorded. Immunohistochemistry for IgG4 was performed on both pancreatic and extrapancreatic tissues and the numbers of IgG4 positive plasma cells were semiquantitatively scored. A control cohort composed of pancreatic adenocarcinoma (n=19) and chronic pancreatitis-not otherwise specified (NOS) (n=14) was also evaluated. Eleven pancreatic specimens, including 2 cases of chronic pancreatitis-NOS and 4 kidneys were evaluated ultrastructurally. The pancreas, bile duct, gall bladder, salivary gland, kidney, and lung lesions were characterized by dense lymphoplasmacytic infiltrates with reactive fibroblasts and venulitis. IgG4 positive plasma cells were identified in all pancreatic and extrapancreatic lesions. The AIP cases showed significantly more pancreatic IgG4 positive plasma cells than chronic pancreatitis-NOS or adenocarcinoma (P=0.001). However, IgG4 positive cells were identified in 57.1% of chronic pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21 resected cases were classified as AIP-D, and 6 as AIP-L, the latter notably showing significantly more IgG4 positive plasma cells than the former (P=0.02). Additionally, clinical and radiologic differences emerged between the 2 groups. Ultrastructurally, electron dense deposits of immune complexes were identified in the basement membranes of 7 of the 9 AIP cases and in 3 of the 4 renal biopsies evaluated. AIP represents the pancreatic manifestation of a systemic autoimmune disease. Clinical and immunologic findings justify the recognition of pancreatic lobulocentric and ductocentric subtypes. Documentation of increased numbers of tissue IgG4 positive plasma cells, although not an entirely specific marker for AIP, may provide ancillary evidence for the diagnosis of a IgG4-related systemic disease.

Adolescent↗
PubMed2006

Advances in the endoscopic management of patients with pancreatic and biliary malignancies.

Major advances in endoscopic techniques to diagnose and manage pancreatic biliary diseases have fundamentally changed the approach to these difficult clinical challenges. The diagnosis of benign and malignant pancreatic-biliary diseases is much more readily obtained through a combination of cross-sectional imaging and endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are the most important endoscopic tools for imaging and accessing the pancreatic biliary system. The review summarizes the major imaging methods for providing a diagnosis of bile duct malignancy, including ERCP, transhepatic cholangiography (THC), and magnetic resonance cholangiopancreatography (MRCP). High quality image examples of cholangiocarcinoma are provided. EUS has provided a new imaging modality for the detection of pancreatic and biliary malignancy. EUS is particularly sensitive for the detection of early pancreatic malignancy. Furthermore, EUS excels at the guidance of fine needle aspiration of pancreatic lesions. Diagnostic tissue acquisition for cholangiocarcinoma remains an important challenge. The endoscopic therapy for pancreatic-biliary malignancy involves the use of stenting which relieves the biliary obstruction commonly seen in these patients.

Biliary Tract Neoplasms↗
PubMed2005

Endoscopic techniques to diagnose and manage biliary tumors.

Malignancies of the bile duct are often suspected in patients with abnormal serum hepatic enzyme levels and obstruction of the biliary system. Although cross-sectional imaging can provide evidence for biliary obstruction and a malignancy arising from the bile duct, a definitive diagnosis is often obtained through the use of endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP), the most commonly performed procedure for cholangiocarcinoma, can provide a tissue diagnosis through brush cytology of the bile duct. Relief from biliary obstruction can be provided with temporary plastic stenting or permanent metal stenting. Photodynamic therapy guided by ERCP may provide improved palliation from biliary obstruction in the future. Endoscopic ultrasonography complements the role of ERCP and may provide a tissue diagnosis through fine-needle aspiration and staging through ultrasound imaging. High-resolution ultrasound images can provide detailed information regarding the relationship between a mass and the bile duct wall. Despite these advances in endoscopic techniques and imaging of the bile duct, a tissue diagnosis often remains elusive in many patients. In the future, molecular markers will be employed to improve the sensitivity for the detection of malignancy in bile duct samples obtained through brushing, aspiration, and biopsy.

Bile Duct Neoplasms↗
PubMed2005

Approach to cystic pancreatic lesions.

Cystic neoplasms of the pancreas represent the best example of a malignant precursor in the pancreas. There are many parallels between pancreatic cystic neoplasms and the colon polyp-cancer sequence. In the past, cystic neoplasms of the pancreas were thought to be relatively rare, composing less than 10% of cancers of the pancreas. With the greater use of cross-sectional imaging, an increasing number of these neoplasms are being seen.

Cholangiopancreatography, Endoscopic Retrograde↗