Caution urged with repeat sentinel lymph node biopsies.
Explore the source record for details and available documents.
Axilla↗
Biomedical subjects
M A Chung
Publications and source records attributed to M A Chung.
New lessons from the sentinel node.
Sentinel node biopsy to determine the presence of metastatic disease in regional lymph nodes has been described in a variety of solid tumors. Sentinel node biopsy has proven that drainage of cancer cells to the regional lymph nodes is an orderly process with metastasis predominantly to one or two nodes first before involvement of subsequent nodes. The use of this technique has resulted in the increased identification of regional metastasis suggesting that patients previously identified as node negative may have unidentified regional metastasis. The clinical significance of these microscopic tumor deposits in lymph nodes remains controversial.
Humans↗
Detection of beta-amyloid peptide aggregation using DNA electrophoresis.
DNA could readily associate with the aggregated forms of the beta-amyloid peptides beta(1-40) and beta(25-35), giving rise to a shift in the electrophoretic mobility of DNA. As a result, DNA was retained at the top of a 1% agarose gel. In contrast, the electrophoretic mobility of DNA was little influenced by the monomeric forms of beta(1-40) and beta(25-30). DNA from different sources such as lambda phage, Escherichia coli plasmid, and human gene showed similar results. However, the electrophoretic mobility of RNA was shifted by the monomeric beta(1-40) and beta(25-35) as well as by the aggregated beta(1-40) and beta(25-35). The association of DNA with the aggregated beta-amyloid peptides could occur at pH 4-9. The inhibitory action of hemin on beta-amyloid aggregation could be confirmed using the DNA mobility shift assay. These results indicate that the DNA mobility shift assay is useful for kinetic study of beta-amyloid aggregation as well as for testing of agents that might modulate beta-amyloid aggregation.
Amyloid beta-Peptides↗
Axillary dissection in the context of the biology of lymph node metastases.
BACKGROUND: Modern breast surgery, as the primary treatment of invasive breast carcinoma, has been evolving over the last century. Aggressive radical surgery, which included chest wall resection, complete axillary clearance and internal mammary node dissection, has slowly changed to a less aggressive approach. This has been based on an improved understanding of the biology of the disease. Over the years, randomized prospective trials, performed at centers all over the world, have demonstrated that axillary dissection does not impact on the overall survival while it helps with loco-regional control of breast cancer. Its major role, at the present time, is limited to staging and prognostication; functions that are equally well served by the limited approach of a sentinel node biopsy. SOURCES: This review is based on the available medical literature involving the biology and organ specificity of the metastatic process, not only in breast cancer but also in other malignancies. In addition, studies pertaining to clinical breast cancer, and the role of surgery in its treatment, were reviewed. The ongoing trials on the role of sentinel node biopsy in the management of the clinically node negative patients are discussed. CONCLUSIONS: This review covers the history, pathophysiology, and clinical basis of the current role of axillary dissection for invasive breast cancer. From the data presented we hope that the medical community will agree that there is no therapeutic role for extended axillary dissection at the current time.
Axilla↗
Biologic and clinical significance of lymphadenectomy.
Interest in the lymphatic system and its relationship to metastases has developed owing to renewed interest in sentinel node biopsy. This article summarizes the anatomy, physiology, and biology of the lymphatic system and lymph node metastases, and reviews studies of lymph node metastases and surgical resection of cancers in different anatomic sites. On the basis of these studies, the authors conclude that lymph node metastasis functions as an indicator of prognosis, not the controlling or determining factor of prognosis. Thus, varying degrees of treatment of regional lymph nodes and metastases do not seem to be controlling factors in the outcome of cancer.
Actuarial Analysis↗
The surgeon's role in outcome in contemporary breast cancer.
Details of surgical removal of invasive breast cancer do not govern survival or cure. They do, however, control local recurrence rates and regional recurrence risk. The surgeon's role in breast cancer in the new millennium is to produce a cosmetic and functional result that is as good as possibly can be achieved while minimizing recurrence. Guidelines for incision placement, tissue volume removal, and nodal removal are critical determinants of cosmetic and functional outcome and need to be appreciated by surgeons.
Biopsy↗
Use of state hospital discharge data to assess the morbidity from rotavirus diarrhea and to monitor the impact of a rotavirus immunization program: A pilot study in Connecticut.
OBJECTIVES: Now that rotavirus vaccines have been licensed and recommended for routine immunization of US infants, there is an urgent need for data to assess the morbidity from rotavirus diarrhea and to monitor the impact of a rotavirus immunization program. In a pilot study, we have assessed the usefulness of state hospital discharge data on diarrhea in children to provide this information by examining data from Connecticut. DESIGN: Retrospective analysis of discharge records from acute care, nongovernmental hospitals in Connecticut. Patients. Children 1 month through 4 years of age with a diarrhea-associated diagnosis listed on the discharge record. Setting. Connecticut, 1987 through 1996. RESULTS: During the 10-year study period, a total of 11 324 diarrhea-associated hospitalizations (49.4 hospitalizations per 10,000 children) were reported. Diarrhea-associated hospitalizations peaked during February through April, especially among children 4 to 35 months of age. The seasonality and age distribution of diarrhea-associated hospitalizations of presumed noninfectious and viral etiologies resembled those of rotavirus-associated hospitalizations. During 1993 to 1996, rotavirus was coded for 10.4% of diarrhea-associated hospitalizations increasing from 8.6% in 1993 to 14.7% in 1996. The unadjusted median cost of a diarrhea-associated hospitalization during 1987 to 1996 and 1993 to 1996 was $1,941 and $2,428, respectively. CONCLUSIONS: Diarrhea causes substantial morbidity in children from Connecticut. The winter seasonal peak of diarrhea-associated hospitalizations in children 4 to 35 months of age coinciding with the peak of rotavirus-specific hospitalizations suggests that rotavirus is an important contributor to the overall morbidity. Although our findings suggest incomplete coding of rotavirus cases, state hospital discharge data should provide sensitive and timely information to monitor the impact of a rotavirus immunization program in Connecticut.
Child, Preschool↗
A fork head/HNF-3 homolog expressed in the pharynx and intestine of the Caenorhabditis elegans embryo.
We have cloned a member of the fork head/HNF-3 family of transcription factors from the nematode Caenorhabditis elegans. Within the predicted DNA binding domain, this gene, called Ce-fkh-1, is 75-78% identical to the Drosophila fork head and rat liver HNF-3 alpha, beta, and gamma genes. Ce-fkh-1 mRNA is highly enriched in embryos. The Ce-fkh-1 gene produces three major transcripts: the longest mRNA retains its original 5'-end but two shorter mRNAs are trans-spliced at the beginning of exons 2 and 3, respectively. In situ hybridization and transgenic Ce-fkh-1::lacZ reporter constructs indicate that the Ce-fkh-1 gene is expressed in both pharynx and intestine of the embryo, beginning at the midproliferation stage. A second phase of Ce-fkh-1 expression occurs in cells of the larval somatic gonad. The pharynx-gut expression of Ce-fkh-1 in the C. elegans embryo is compared with expression of fork head throughout the gut of Drosophila embryos and with expression of HNF-3 (alpha beta gamma) in the endoderm of mammalian embryos. Such conserved patterns of gene expression point to universal features of gastrulation and of digestive tract formation.
Amino Acid Sequence↗
Preoperative therapy for advanced pelvic malignancy by isolated pelvic perfusion with the balloon-occlusion technique.
BACKGROUND: Although the technique of isolated pelvic perfusion dates back to the time of Creech (1959) and has been used by a variety of authors to treat unresectable neoplasms, the inherent complexity of the open procedure limited its widespread use. We simplified the technique through use of the balloon-occlusion technique for aortic and caval control. Our initial efforts used this technique for unresectable pelvic cancer, but recently we used this as preoperative therapy for advanced pelvic malignancy. METHODS: Isolated pelvic perfusion was accomplished by placement of balloon-occlusion catheters (Fogerty 8) in the aorta and inferior vena cava (IVC) at L3 vertebral body level via the common femoral artery and vein and establishing inflow and outflow catheter connections to a hemodialysis pump that generated a flow rate of 150-300 ml/min. Chemotherapy drugs were infused at times 0, 10, and 20 min. 5-Fluorouracil (5-FU; 1,500 mg/M2), cis-platinum (50-100 mg/M2), and mitomycin (15-20 mg/M2) were given by normothermic perfusion over a 45-min period. Forty isolated perfusions were carried out in 25 patients. Patients were evaluated by clinical examination, biochemical tests, computed tomography (CT) and magnetic resonance imaging (MRI) scans, and surgical exploration. RESULTS: Pelvic perfusion generally achieved pelvic systemic exposure ratios (area under the curve) between 5 and 10:1 for all three drugs: mean ratios were 11.4 (5-FU), 6.0 (cisplatin), and 9.0 (mitomycin). The amount of leaking to the systemic circuit ranged from 28 to 38%. Of 15 patients treated for palliation, there was one objective partial response (PR). Ten patients had symptomatic improvement of pain, two had complete pain relief (CR), and eight had partial pain relief, ranging from 3 weeks to 3 months (median, 5 weeks). Six of 10 patients with adequate carcinoembryonic antigen (CEA) follow-up data had a reduction in CEA levels (mean change, 35 units). Of 10 preoperative patients, there was one CR among five rectal cancer patients; and four of five PRs among patients with other pelvic malignancies: two PRs in patients with epidermoid cancer and one PR each in patients with endometrial cancer and metastatic anorectal melanoma. CONCLUSION: Pelvic perfusion by a simplified balloon-occlusion technique provides palliation for most patients with advanced pelvic malignancy and may increase resectability and improve tumor control in patients amenable to resection.
Adult↗
Surgical management and treatment of gastric and duodenal fistulas.
Gastroduodenal fistulas compose only a small portion of gastrointestinal fistulas. They usually occur in the postoperative setting in association with an anastomotic leak. As with all fistulas, attention to adequate supportive care is needed. Interventional endoscopy may play a role in the future. The three surgical management approaches include exclusion, resection, and closure of the fistula. The success rate of closure ranges from 25% to 75% with supportive care only to 100% with proper surgical management.
Duodenal Diseases↗
A gut-to-pharynx/tail switch in embryonic expression of the Caenorhabditis elegans ges-1 gene centers on two GATA sequences.
The Caenorhabditis elegans ges-1 gene (gut esterase No. 1) is expressed only in the intestinal lineage, beginning when the developing gut has only four to eight cells. We analyze the sequence requirements for this tissue-specific gene regulation by injecting deleted/mutated constructs of the ges-1 gene into a viable ges-1 (null) strain of worms and assaying heritably transformed embryos by esterase histochemistry. Many deletion constructs accurately reconstitute the wildtype gut-specific ges-1 expression. However, deletions in the neighborhood of 1100 bp upstream of the ges-1 ATG abolish ges-1 expression in the developing gut, while at the same time activating ges-1 expression in cells of the pharynx/tail that appear to belong to the sister lineage of the gut. Deletions of a 36-bp DNA region containing two tandem WGATAR sequences are sufficient to cause this gut-to-pharynx/tail switch in expression pattern. Deletion of either one of the WGATAR sites or deletion of an adjoining downstream region directs ges-1 expression only in a restricted set of cells of the anterior gut. The ges-1 GATA region acts like a gut-specific enhancer in that: (i) it restores ges-1 gut expression when reinserted elsewhere into the GATA-deleted ges-1 gene; and (ii) multiple copies direct gut expression of an hsp16-lacZ reporter gene. The ges-1 GATA-region also acts as the site of the pharynx/tail repression in that reinsertion elsewhere into the GATA-deleted ges-1 construct causes repression of ges-1 in the pharynx/tail. However, multiple copies of the GATA region are not able to repress the heat-induced expression of an hsp16-lacZ reporter gene, suggesting that the pharynx/tail repression mechanism is specific to the ges-1 environment. Finally, mutation rather than deletion of the individual GATA sequences suggests that gut activation and pharynx/tail repression may be due to separate factors. We present a molecular model that summarizes these results. The ges-1 control circuitry appears surprisingly complex for what might have been expected to be the simplest possible example of a nonessential gene expressed early in a clonal embryonic lineage.
Animals↗
The gut esterase gene (ges-1) from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae.
The ges-1 gene codes for a non-specific carboxylesterase that is normally expressed only in the intestine of the nematode Caenorhabditis elegans. In the current paper, we describe the cloning and characterization of the ges-1 gene from C. elegans, as well as the homologous gene from the nematode Caenorhabditis briggsae. The ges-1 esterases from the two nematodes are 83% identical at the amino acid level and contain regions of significant similarity to insect and mammalian esterases; these conserved regions can be identified with residues believed to be necessary for esterase function. The ges-1 mRNAs from both C. elegans and C. briggsae are trans-spliced. The coding regions, the codon bias and the splicing signals of the two ges-1 genes are quite similar and most (6/7) of the intron positions are retained precisely. Yet, the flanking sequences of the two ges-1 genes appear to have diverged almost completely. For example, the C. elegans ges-1 5'-flanking region (as well as several introns) contains copies of three different SINE-like sequences, previously identified near the hsp-16 genes, near the unc-22 gene and in a repetitive element CeRep-3; none of these elements are found in the C. briggsae ges-1 gene. We show that: (1) the C. elegans ges-1 gene can be used to transform C. briggsae, whereupon expression of the exogenous ges-1 gene is confined to the C. briggsae intestine; (2) the ges-1 homologue cloned from C. briggsae can be transformed into C. elegans, whereupon it is expressed largely in the C. elegans intestine; and (3) a 5'-deletion of the C. elegans ges-1 gene that we have previously shown to be expressed in the C. elegans pharynx is also expressed in the pharynx of C. briggsae (either in the presence or absence of vector sequences). These results suggest that the ges-1 gene control circuits have been maintained between the two nematode species, despite the divergent 5'-flanking sequences of the gene. This raises the question of the evolutionary distance between C. elegans and C. briggsae and we attempt to estimate the C. elegans-C. briggsae divergence time by analysing the rate of synonymous substitutions in coding regions of ges-1 and six other C. elegans-C. briggsae gene pairs. We propose a new method of analysis, which attempts to remove rate differences found between different genes by extrapolating to zero codon bias.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Cullen's sign: it doesn't always mean hemorrhagic pancreatitis.
Periumbilical ecchymosis, Cullen's sign, is most often considered a sign of hemorrhagic pancreatitis. We present a case of splenic rupture secondary to infectious mononucleosis in a middle-aged patient whose presenting complaint was the presence of Cullen's sign, secondary to the hemoperitoneum. The splenic rupture was managed conservatively, and the Cullen's sign resolved within 14 days of presentation.
Acute Disease↗
Spatial control of gut-specific gene expression during Caenorhabditis elegans development.
The nematode Caenorhabditis elegans was transformed with constructs containing upstream deletions of the gut-specific ges-1 carboxylesterase gene. With particular deletions, ges-1 was expressed, not as normally in the gut, but rather in muscle cells of the pharynx (which belong to a sister lineage of the gut) or in body wall muscle and hypodermal cells (which belong to a cousin lineage of the gut). These observations suggest that gut-specific gene expression in C. elegans involves not only gut-specific activators but also multiple repressors that are present in particular nongut lineages.
Animals↗
Mesenteric cysts in children.
Mesenteric cysts are rare intraabdominal lesions of childhood that may vary in presentation from an asymptomatic mass to an acute abdomen. From 1970 to 1990, 15 children were diagnosed and treated for mesenteric cysts at Ste Justine Hospital in Montreal. The ages ranged from birth to 18 years (average age, 6 years). There were 9 boys and 6 girls. Ten patients required emergency surgery and five underwent elective surgery. The main presenting symptom was abdominal pain. Ten patients had preoperative ultrasounds that were diagnostic for a cystic mass in all patients. The second most frequent preoperative diagnosis was appendicitis. The cysts were located in the small bowel mesentery in 5 cases, the base of the mesentery with retroperitoneal extension in 4 cases, the transverse mesocolon in 4 cases, and the gastrocolic ligament in 2 cases. Operative procedures performed included complete cyst excision (9 patients), complete excision with intestinal resection (5 patients), and drainage of the cyst (1 patient). The only recurrence in this series occurred after drainage. One other patient had recurrence of a mesenteric cyst following resection performed elsewhere. Mesenteric cysts are rare in children, are usually symptomatic, and are most commonly misdiagnosed as acute appendicitis. Accurate preoperative diagnosis is possible with current ultrasonographic imaging techniques. Complete cyst resection is the procedure of choice and results in an excellent outcome.
Abdominal Pain↗
Pneumatosis and pneumoperitoneum in chronic idiopathic intestinal pseudoobstruction.
Chronic idiopathic intestinal pseudoobstruction is a diagnosis of exclusion for the rare patient with severe small bowel atony without any demonstrable organic cause. The very poor prognosis associated with this disease has been somewhat improved with the advent of parenteral nutrition; nevertheless, these patients follow a stormy course characterized by malnutrition, recurrent obstruction, infection, hemorrhage, and perforation. We describe a 16-year-old boy with this disease who presented to us with vague abdominal pain and pneumoperitoneum. Laparotomy showed pneumatosis cystoides intestinalis without intestinal perforation. The presence of free air in the abdominal cavity is an almost pathognomonic sign of intestinal perforation. Pneumatosis cystoides intestinalis is one of the very few nonsurgical causes of pneumoperitoneum. Beyond the neonatal period, in which it is the hallmark of necrotizing enterocolitis, it has been described in patients with severe obstructive lung disease, in collagenous disorders, and in the short-bowel syndrome. In the present case, it may have resulted from chronic intestinal distension, allowing air under pressure to dissect through the bowel wall. The challenge of such a unique association of conditions lies in the avoidance of unnecessary surgery in a chronic, essentially nonsurgical disease while avoiding unnecessary delay in a possibly acute surgical event.
Child↗
An acid phosphatase as a biochemical marker for intestinal development in the nematode Caenorhabditis elegans.
We describe an acid phosphatase enzyme (EC 3.1.3.2) that is localized to the intestine of the nematode Caenorhabditis elegans and that should serve as a convenient biochemical marker for gut differentiation. In adult worms, acid phosphatase activity is located along the edge of the gut lumen in the vicinity of the intestinal brush border. All but the anterior six cells of the intestine stain for phosphatase activity; the nonstaining cells all descend from the Ea(l/r)(a/p)a cells. Acid phosphatase activity is low in oocytes and early embryos but increases substantially when embryos reach late morphogenesis stage; this increase corresponds to the appearance of a major band of acid phosphatase activity detectable on isoelectric focusing gels. We designate this band as the product of the pho-1 gene. The pattern of acid phosphatase expression in several embryonic mutants suggests that pho-1 expression in the developing intestine is lineage autonomous. We induced an isoelectric focusing variant in the pho-1 enzyme and used this to map the pho-1 locus about 1.5 map units to the left of center of chromosome II. We purified the pho-1 enzyme to homogeneity (6500-fold purification; 4% recovery of activity); the pho-1 acid phosphatase is a homodimeric glycoprotein with a subunit molecular weight of 55,000 Da. This paper establishes a new experimental system with which to investigate the molecular basis of lineage-specific gene expression during C. elegans development.
Acid Phosphatase↗
Production of null mutants in the major intestinal esterase gene (ges-1) of the nematode Caenorhabditis elegans.
The ges-1 gene of the nematode Caenorhabditis elegans codes for a nonspecific carboxylesterase that is expressed only in the intestinal lineage. This esterase has turned out to be a convenient biochemical marker for lineage-specific differentiation. In the present paper, we describe the production of several C. elegans strains that lack detectable activity of the ges-1 esterase. To isolate these ges-1 null strains, we first produced a strain of hermaphrodites in which the wild-type copy of the ges-1 gene was stably balanced over a previously isolated isoelectric focusing allele, ges-1(ca6); this parental strain was then mutagenized with EMS and isoelectric focusing gels were used to identify progeny populations that lacked either ges-1(+) or ges-1(ca6) esterase activity. This method is a straightforward and general approach to obtaining null mutations in any gene that has a biochemical or immunological assay. The ges-1 gene is not essential to worm survival, development or reproduction. Furthermore, lack of the ges-1 product has no obvious effect on the ability of worms (containing either normal or greatly reduced levels of acetylcholinesterases) to survive exposure to esterase inhibitors. The ges-1 gene product provides roughly half of the total esterase activity measured in crude extracts of L1 larvae or mixed worm populations. However, histochemical staining of individual ges-1(0) embryos shows that the ges-1 esterase is the first and essentially the only esterase to be produced during embryonic development, from the midproliferation phase up to at least the twofold stage of morphogenesis. These ges-1(0) strains now allow us to investigate the developmental control of the ges-1 gene by DNA-mediated transformation, in which the ges-1 gene acts as its own reporter.
Animals↗