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Biomedical subjects

E Dougherty

Publications and source records attributed to E Dougherty.

At least 19 recordsLinked to original sources

A clinical scoring system predicts the yield of diagnostic laparoscopy in patients with potentially resectable hepatic colorectal metastases.

BACKGROUND: Laparoscopy may identify occult metastatic disease and prevent unnecessary laparotomy in some patients with potentially resectable colorectal liver metastases but is unnecessary in the majority of individuals who undergo resection. The objectives of the current study were to assess the impact of laparoscopy after extensive preoperative imaging and to determine whether a preoperative clinical risk score can identify those patients most likely to benefit from the procedure. METHODS: Between December 1997 and July 1999, 103 consecutive patients with potentially resectable colorectal liver metastases underwent laparoscopy prior to planned laparotomy and partial hepatectomy. Surgical findings, length of hospital stay, and hospital charges were analyzed. Patients were assigned a clinical risk score (CRS) based on five factors related to the primary tumor and the hepatic disease. The likelihood of finding occult unresectable disease and the yield of laparoscopy were analyzed with respect to the CRS. RESULTS: Seventy-seven patients (75%) underwent resection. Laparoscopy identified 14 of 26 patients with unresectable disease, 10 of whom were spared an unnecessary laparotomy. In patients who underwent biopsy only, the laparoscopic identification of unresectable disease shortened the hospital stay (1.2 +/- 0.6 days vs. 5.8 +/- 2.3 days; p = 0.0001) and reduced the total hospital charges by 55% (P = 0.0001). The CRS predicted the likelihood of occult unresectable disease, which was 12% in those with a score < or = 2 but increased to 42% in those with a score > 2 (P = 0.001). If laparoscopy were used only in high risk patients (CRS > 2), 57 laparoscopies would have been avoided and the net savings doubled. CONCLUSIONS: With extensive preoperative imaging, the vast majority of patients with potentially resectable hepatic colorectal metastases do not benefit from laparoscopy. However, in the minority of patients with occult unresectable disease, laparoscopy prevents unnecessary laparotomy and reduces hospital stay and the total hospital charges. The CRS, previously shown to predict survival after hepatic resection, identifies those high risk patients most likely to benefit from laparoscopy and may improve resource utilization.

Aged↗

Gene-expression profiles in hereditary breast cancer.

BACKGROUND: Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles. METHODS: RNA from samples of primary tumor from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. RESULTS: Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each other. An analysis of variance between the levels of gene expression and the genotype of the samples identified 176 genes that were differentially expressed in tumors with BRCA1 mutations and tumors with BRCA2 mutations. Given the known properties of some of the genes in this panel, our findings indicate that there are functional differences between breast tumors with BRCA1 mutations and those with BRCA2 mutations. CONCLUSIONS: Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancers with BRCA2 mutations. Our results suggest that a heritable mutation influences the gene-expression profile of the cancer.

Algorithms↗

Analysis of expression patterns: the scope of the problem, the problem of scope.

Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics.

Cluster Analysis↗

Molecular classification of cutaneous malignant melanoma by gene expression profiling.

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

Adult↗

Hand-assisted laparoscopic liver resection: lessons from an initial experience.

BACKGROUND: Recent innovations in laparoscopic instrumentation make routine resection of solid organs a clinical possibility. HYPOTHESIS: Hand-assisted laparoscopic liver resection is a safe and feasible procedure for solitary cancers requiring removal of 2 segments of liver or less. DESIGN AND PATIENTS: Eleven patients with liver tumors deemed technically resectable by laparoscopic techniques were subjected to laparoscopic evaluation and attempted hand-assisted laparoscopic resection between July 1998 and July 1999. During the same period, 230 patients underwent open liver resection. SETTING: Tertiary care referral center for liver cancer. MAIN OUTCOME MEASURES: Success of laparoscopic resection, reasons for conversion to open liver resection, blood loss, tumor clearance margin, complications, and length of hospital stay. RESULTS: Five patients underwent successful resection by the hand-assisted laparoscopic technique. Data from the 5 successful cases and the 6 aborted cases are presented to outline the issues and the lessons learned. CONCLUSIONS: In selected patients, hand-assisted laparoscopic liver resection can be safely performed and might have potential advantages over traditional liver resection if the tumor is limited to the left lateral segment or is at the margins of the liver.

Adult↗

Positive peritoneal cytology predicts unresectability of pancreatic adenocarcinoma.

BACKGROUND: Peritoneal cytology is clinically useful in gastric and gynecologic malignancies. Its role in pancreatic adenocarcinoma remains less well defined. Controversy exists as to the relationship between percutaneous fine needle aspiration (FNA) of the pancreas and shedding of malignant cells with the peritoneum. The aim of this study was to determine whether positive peritoneal cytology (PPC) predicts unresectability of pancreatic adenocarcinoma and impacts on overall survival. In addition, the study aimed to determine whether antecedent FNA increases the incidence of PPC. STUDY DESIGN: Between January 1993 and June 1996, 228 patients with radiographically resectable pancreatic adenocarcinoma underwent laparoscopic staging. Specimens were taken from right and left upper quadrants at the beginning of laparoscopy. Various prognostic factors were analyzed. RESULTS: PPC was identified in 34 patients (15%). Of patients that had an antecedent FNA, 20% had PPC, and 13% of those without an antecedent FNA had PPC (p = 0.22). The majority of patients with PPC had stage IV disease (26 of 34 [76%]) and only 8 (24%) had no evidence of metastases. Overall survival was significantly higher in patients with negative peritoneal cytology (NPC) compared with PPC (p<0.0006). PPC had a positive predictive value of 94.1%, specificity of 98.1%, and a sensitivity of 25.6% for determining unresectability of pancreatic adenocarcinoma. PPC was not an independent prognostic variable for survival on multivariate analysis. CONCLUSIONS: PPC is associated with advanced disease and is highly specific in predicting unresectability of pancreatic adenocarcinoma, resulting in decreased survival. Antecedent FNA is not associated with an increased the incidence of PPC, nor does it significantly impact on overall survival.

Adenocarcinoma↗

Emerging role of laparoscopy in the diagnosis of lymphoma.

PURPOSE: The results of laparoscopic procedures on patients with suspected or known lymphoma were analyzed to review the application and define the role of laparoscopy in lymphoma. PATIENTS AND METHODS: The hospital records of 94 patients who underwent 101 procedures between June 1993 and October 1996 were reviewed for demographic and clinicopathologic information. RESULTS: The procedure was diagnostic in 85 patients, either at primary presentation (48 patients), possible relapse (21 patients), in the course of treatment (eight patients), or of a liver lesion (eight patients). In the remaining 16 patients, it was used to stage possible intraabdominal disease. Twenty-seven patients had a previous unsuccessful diagnostic procedure. There were no operative deaths and eight postoperative complications (8%). The laparoscopy revealed non-Hodgkin's lymphoma (NHL) in 48 patients, Hodgkin's disease (HD) in 14 patients, other neoplastic conditions in six patients, and benign conditions in 33 patients. There was adequate information in all procedures in which lymphoma was diagnosed for treatment decisions. There was one false-negative and one nonresult for technical reasons. Ten patients commenced chemotherapy before discharge after a median delay of 3.5 days. In five of 24 patients (21%) with recurrent or persistent lymphoma, the precise diagnosis was significantly different from the original one. CONCLUSION: From our experience, laparoscopy can safely provide tissue samples of suspected lymphoma for full diagnostic analysis. It should be considered when percutaneous biopsy is not technically possible, when chromosomal or genetic analysis is needed for treatment decisions, or when the results of percutaneous biopsy are inadequate to make therapeutic decisions.

Abdominal Neoplasms↗

The value of minimal access surgery in the staging of patients with potentially resectable peripancreatic malignancy.

OBJECTIVE: The purpose of this study was to determine if an endosurgical approach that mimics open exploration would improve the accuracy of simple diagnostic laparoscopy. SUMMARY BACKGROUND DATA; Most patients with peripancreatic malignancy are found at exploration to be unable to undergo resection. Laparoscopy has been suggested as a sensitive method for detecting metastatic disease in this group of patients. However, the ability to assess resectability with simple diagnostic laparoscopy remains relatively low (<40%). METHODS: Between December 1992 and August 1994, 115 patients with radiologically resectable peripancreatic tumors underwent extended laparoscopy before undergoing a planned curative resection. This technique required assessment of the peritoneal cavity, liver, lesser sac, porta hepatis, duodenum, transverse mesocolon, and celiac and portal vessels. RESULTS: Sixty male and 55 female patients were included in the current study. The pancreatic head was involved in 74 patients (64%), followed by the body in 21 (18%), tail in 8 (7%), ampulla in 8 (7%), duodenum in 3 (3%), and distal bile duct in 1 (1%). An abdominal computed tomography (CT) scan was performed for all patients before laparoscopy, ultrasonography for 74 patients (64%), endoscopic retrograde choleangiopancreatography for 59 patients (51%), and mesenteric angiography for 9 patients (8%). Pneumoperitoneum was established successfully in all but 2 cases (98%). A complete examination of 108 patients was performed. Sixty-seven patients were considered to have resectable disease, and 61 resections were performed. Laparoscopy failed to identify hepatic metastases in 5 patients and portal venous encasement in 1 patient. Unresectable disease was identified in 41 patients. Hepatic metastases were observed in 20 patients, mesenteric vascular encasement in 14, extrapancreatic/peritoneal involvement in 16, and celiac or portal lymphatic metastases in 8. There were no intraoperative or postoperative complications related to the laparoscopic procedure. The positive predictive index, negative predictive index, and accuracy of laparoscopy were 100%, 91%, and 94%, respectively. CONCLUSIONS: This study demonstrates that extended laparoscopy is accurate and safe and makes exploration unnecessary in many patients with potentially resectable peripancreatic malignancy. In this series, 76% of patients explored were resected, compared with the authors' experience between 1983 and 1993 of 35%. The authors believe that laparoscopy is an important component in the staging of this group of patients and should be performed before exploration.

Adult↗

Ultrastructural hepatocellular features associated with severe hepatic lipidosis in cats.

In this study, we compared hepatic ultrastructure in healthy cats, in cats with severe hepatic lipidosis, and in cats with experimentally induced, chronic, extrahepatic bile duct occlusion. Ultrastructural features unique to the lipidosis syndrome included an apparent reduction in number of peroxisomes and alteration in their morphologic features. The quantity of endoplasmic reticulum, Golgi complexes, and lysosomes was subjectively reduced, and paucity of cytosolic glycogen was observed. Bile canaliculi appeared collapsed because of cytosolic distention with lipid. Mitochondria were reduced in number and were markedly pleomorphic. Cristae assumed a variety of shapes, lengths, and orientations. Ultrastructural features of bile duct occlusion were similar to those described in other species and differed from those in cats with hepatic lipidosis.

Animals↗

Viral and host cellular transcription in Autographa californica nuclear polyhedrosis virus-infected gypsy moth cell lines.

Infection of two gypsy moth cell lines (IPLB-Ld652Y and IPLB-LdFB) by the Autographa californica multiple-enveloped nuclear polyhedrosis virus (AcMNPV) is characterized by extremely attenuated viral protein synthesis followed by a total arrest of all viral and cellular protein production. In this study, AcMNPV- and host cell-specific transcription were examined. Overall levels of viral RNAs in infected gypsy moth cells were, at most measured times, comparable to RNA levels from an infected cell line (TN-368) permissive for AcMNPV replication. Northern blot (RNA) analyses using viral and host gene-specific probes revealed predominantly normal-length virus- and cell-specific transcripts postinfection. Transport of viral RNAs from the nucleus to the cytoplasm and transcript stability in infected gypsy moth cells also appeared normal compared with similar parameters for AcMNPV-infected TN-368 cells. Host cellular and viral mRNAs extracted from gypsy moth and TN-368 cells at various times postinfection and translated in vitro yielded similar spectra of host and viral proteins. Treatment of infected gypsy moth cells with the DNA synthesis inhibitor aphidicolin eliminated the total protein synthesis shutoff in infected IPLB-LdFB cells but had no effect on protein synthesis inhibition in infected IPLB-Ld652Y cells. The apparent selective block in the translation of viral transcripts early in infection and the absence of normal translation or transcription of host cellular genes at later times is discussed.

Animals↗

Comparison of persistence of seven bovine viruses on bovine embryos following in vitro exposure.

The ability of seven cytopathic strains of bovine viruses to adhere to the zona pellucida of six-to-eight day-old bovine embryos were compared. Embryos were exposed to virus by placing them either in virus suspensions or by culturing them on infected bovine turbinate cultures for 18-24 h. After exposure to bovine virus diarrhea virus (BVDV), infectious bovine rhinotracheitis virus (IBV), bluetongue virus (BTV), pseudorabies virus (PRV), vesicular stomatitis virus (VSV), parainfluenza 3 virus (PI3), or bovine enterovirus virus (BEV), the embryos were tested for virus by culture in bovine turbinate cells and by morphological examination using electron microscopy (EM). A special technique to minimize loss of embryos processed for EM was developed. More embryos had viral particles on the surface of the zona pellucida after exposure to 18-24 hour infected cell cultures than did embryos exposed to viral culture suspensions. The most dramatic finding was that BTV adhered in large numbers to the surface of the zona pellucida of exposed embryos. IBRV, PRV, and VSV comprised an intermediate group, with virions occasionally detected on the surface of exposed embryos after 5 washes. Therefore, extensive washing is required. The PI3 and BEV were easily removed from embryo-exposed virus by washing. BVD was difficult to identify morphologically, making assessment by EM unreliable. There was no evidence that any one of the seven viruses penetrated the intact zona pellucida. Using a micromanipulator, 42 embryos were also directly inoculated through the zona pellucida with +/- 50 picoliters of virus inoculum or medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mobile lithotripsy services: best bet for most hospitals.

During its short history, extracorporeal shock wave lithotripsy has revolutionized the treatment of kidney stones and may well have a substantial impact on gallstone treatment. The two technologies are potential money makers for hospitals if properly planned for and conceived. For the majority of hospitals, shared arrangements, whether they involve leases or joint ventures, are the key to a successful lithotripsy program. Rural and midsized communities have the greatest need for renal lithotripsy, and hospitals in these areas should explore mobile programs. Urban hospitals located in areas where there is already adequate access to lithotripters are well advised to work with established programs unless the price of lithotripters drops significantly. The demand for biliary lithotripsy remains uncertain, but one thing is clear: hospitals that don't prepare for it now will be left behind once the technology finds it niche.

Hospital Shared Services↗

Hospitals cannot afford to be without access to MRI.

Although practicing state-of-the-art diagnostic medicine is impossible without access to magnetic resonance imaging, this high-ticket technology is a mixed blessing in an era of cost containment. The good news is that MRI's diagnostic capabilities continue to grow, and the prices for scanners are dropping. However, MRI services remain expensive, and reimbursement is declining. To get the maximum benefit from MRI, physicians must stay up to date with the latest advances, a task that hospitals can facilitate through educational programs. Hospitals need to plan carefully for the introduction or expansion of MRI services, but the end result will be better patient care.

Data Collection↗