PubMed Health⌕ Search

Biomedical subjects

Kevin D Lye

Publications and source records attributed to Kevin D Lye.

11 recordsLinked to original sources

From the lumen to the laparoscope.

Throughout the ages, the issues that have defined the management of disease processes have been particularly exemplified in the gastrointestinal tract. The use of gas lamps and candles with reflectors by Bozzini, Segalas, Cruise, and Fisher (19th century) allowed for some ingress into both the upper and lower gastrointestinal tract. Von Mikulicz, Leiter, Nitze, Kelling, and Jacobaeus contributed to the development of rigid instruments that could be used endoscopically or laparoscopically. Endoscopic efforts were amplified and extended by Rosenheim, Sternberg, Wolf, and, finally, Schindler, who not only introduced novel lens systems but also for the most part overcame the problems of flexibility and illumination. Bernheim, Ruddock, Veress, and Palmer made significant technical and clinical contributions to abdominal cavity exploration. The subsequent application of Hopkins and Kapany's work on optics, and the development by Hirschowitz and Curtiss of the flexible fiber optic endoscope, enabled the design of instruments that would allow the appropriate illumination and vision of both the farthest reaches of the bowel as well as the interior of the abdomen. Thus, the same endoscopic instruments coupled with a surgical interest in diagnostic laparotomy allowed for the evolution of minimally invasive surgery along a similar timescale. The cycle whereby diagnostic laparotomy in the early part of the century was supplanted by endoscopy and laparoscopy has now attained full circle whereby laparoscopy has evolved from a diagnostic procedure into one with major therapeutic applications and is perceived as the state-of-the-art technique for a wide variety of operations, including appendectomy, cholecystectomy, hernia repair, fundoplication, splenectomy, colectomy, and gastrointestinal anastomoses.

Cholangiopancreatography, Endoscopic Retrograde↗

A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem?

OBJECTIVES: Interest in gastric carcinoid tumors has amplified considerably given the biological establishment of their relationship to gastrin and advances in the elucidation of the pathobiology of such lesions. The recognized propensity of acid-suppressing agents such as the proton pump inhibitor class of drugs to increase plasma gastrin levels has been proposed as a causal relationship in the apparent increase in the identification of such lesions although the increased prevalence of endoscopy and the enhanced awareness of pathologists have also been considered as contributory factors. We sought to examine if there has been an increase in gastric carcinoid incidence time correlative with these parameters. METHODS: Carcinoid tumor cases from the End Results Group (1950-1969) and the Third National Cancer Survey (TNCS) (1969-1971) databases were combined with the most recent release of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry (1973-1999); these three datasets revealed 13715 carcinoid cases, of which 562 were gastric in origin. Age-adjusted analyses as well as population-based gender and race correction ratios were completed in conjunction with United States decennial census data. To allow a finer granularity in incidence trends, the SEER database was divided into early (1973-1991) and late (1991-1999) subsets. RESULTS Since 1950, the percentage of gastric carcinoids among all gastric malignancies has increased from 0.3% to 1.77%. Since 1969, the proportion of gastric carcinoids among all enteric carcinoid lesions has increased from 2.4% to 8.7%. Age-adjusted incidence rates among male, female, black, and white population subsets have all increased since the TNCS time period, with the greatest increase (800%) noted in white females. The male:female ratio has fallen from 0.90 to 0.54. The occurrence of synchronous or metachronous noncarcinoid tumors with gastric carcinoid tumors has decreased by 26% during the course of SEER data collection. The 5-yr survival rate for gastric carcinoids overall has risen from 51% to 63% during the same time period. CONCLUSIONS: Gastric carcinoids have increased in incidence over the last 50 yr. Differential increases in predominance across gender and race subdivisions may reflect genetic-based propensities (or protection) for gastric carcinoid tumors among certain ethnic populations. Increased endoscopic surveillance and associated sophisticated pathological evaluation of gastric biopsies undoubtedly are responsible for some of the observed increase in the incidence of gastric carcinoid tumors. These data allow no specific role to be assigned to the effects of acid-suppressive medications. Nevertheless the role of such agents cannot be discounted at this time since the time frame of the increased incidence is somewhat comparable to the introduction of these agents as is the known biological effect of gastrin on ECL cell proliferation.

Aged↗

A 5-decade analysis of 13,715 carcinoid tumors.

BACKGROUND: Carcinoid tumors represent an unusual and complex disease spectrum with protean clinical manifestations. This compilation of several large United States-based databases comprising patients from 1950 to 1999 examines 13,715 carcinoid tumors and provides epidemiologic information regarding the natural history and evolution of the detection and diagnosis of this entity. METHODS: The authors evaluated 10,878 carcinoid tumors that were identified by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) from 1973 to 1999 in addition to 2837 carcinoid tumors that were registered previously by two earlier NCI programs. To the authors' knowledge, this represents the largest current epidemiology series addressing carcinoid tumors to date. RESULTS: Specific trends in incidence for carcinoid tumors of certain sites were identified. Among the most recently collected subset of data, sites that demonstrated the greatest incidence of carcinoids were the gastrointestinal tract (67.5%) and the bronchopulmonary system (25.3%). Within the gastrointestinal tract, most carcinoid tumors occurred in the small intestine (41.8%), rectum (27.4%), and stomach (8.7%). For all sites, age-adjusted incidence rates were highest in black males (4.48 per 100,000 population per year). Associated noncarcinoid tumors were frequent in conjunction with small intestinal (29.0%), gastric (20.5%), colonic (20.0%), and appendiceal (18.2%) carcinoids. The highest percentages of nonlocalized lesions were noted for cecal (81.5-83.2%) and pancreatic (71.9-81.3%) carcinoids, whereas the highest percentage of localized disease was found among rectal (81.7%), gastric (67.5%), and bronchopulmonary (65.4%) carcinoids. The best 5-year survival rates were recorded for patients with rectal (88.3%), bronchopulmonary (73.5%), and appendiceal (71.0%) carcinoids; these tumors exhibited invasive growth or metastatic spread in 3.9%, 27.5%, and 38.8% of patients, respectively. CONCLUSIONS: Carcinoids appear to have increased in overall incidence over the past 30 years; for some sites, this trend has been evident for nearly half a century. Recent marked increases in gastric and rectal carcinoids and a concomitant decrease in appendiceal carcinoid incidence may be due in part to varying rules of registration among the compiled databases examined in this report or to improvements in diagnostic technology; increased awareness of and about carcinoid tumors also may play a significant role. In 12.9% of all patients with carcinoid, distant metastases already were evident at the time of diagnosis; the overall 5-year survival rate for all carcinoid tumors, regardless of site, was 67.2%. These findings bring into question the widely promulgated relative benignity of carcinoid disease. Certain carcinoid tumors, such as those of the rectum, appear to be over-represented among the black and Asian populations within the United States, suggesting the role of genetics in the development of this intriguing disease.

Carcinoid Tumor↗

Carcinoid tumors of the stomach.

Interest in gastric carcinoid tumors has in recent time amplified considerably as the understanding of both their biological background and clinical significance has developed. The increase in identification associated with the widespread availability of upper gastrointestinal endoscopy has facilitated diagnosis. In addition concern related to the consequences of long-standing hypergastrinemia generated by the use of potent acid-suppressive medications has augmented both clinical and scientific focus on gastric neuro endocrine issues. The elucidation of the regulatory mechanisms of the progenitor cell (ECL cell) of the gastric carcinoid tumor, the refinement of a pathological grading system for ECL cell proliferation, and the availability of specific immunohistologic identification techniques have further amplified the characterization of this lesion. Although the putative malignant potential of gastric carcinoids may ultimately be of only modest concern in a background of hypergastrinemia its relationship to gastric adenocarcinoma is still enigmatic and worthy of further consideration. This review will describe the molecular interrelationship between low-acid states, gastrin, and ECL cell proliferation and will discuss the pathological classification of the distinct types of gastric carcinoid tumors. In addition, the clinical rationale of current diagnostic and therapeutic strategies will be examined, providing a logical basis for the formulation of appropriate management strategies for patient care.

Adenocarcinoma↗

Historical perspectives on the treatment of gastroesophageal reflux disease.

The current vogue in the historical evolution of the management of the problem of reflux is represented by augmentation procedures for the lower esophageal sphincter. Rather than employ a transperitoneal approach, these are directed at the sphincter by the transesophageal route and include stitching, collagen injection and radio-frequency-induced fibrosis. It is however probable that these techniques will suffer all the drawbacks of any mechanical intervention but somewhat decrease the morbidity of open, albeit minimally invasive surgery. Similarly, a specific pharmacotherapeutic probe targeting the lower esophageal sphincter, while long fantasized, remains to be identified.

Gastroesophageal Reflux↗

Gastric stem cells: an update.

Cells of the gastric mucosa undergo constant renewal, the rate depending on the health of the tissue (inflammation, ulceration, carcinogenesis). While much attention has been focused on the mechanism of mucosal damage and the pathogenesis of ulceration, there has recently been the recognition that elucidation of the nature of the gastric stem cell lineages as well as the regulators of phenotype expression of this system may yield considerable biological information as well as open the door to the identification of areas of therapeutic relevance. Chimeric and X-inactivation studies in mice and humans demonstrate that each region of the gastric mucosa is morphologically diverse (antrum is different to the fundus), with its own repertoire of cell types and glandular structures. The current evidence suggests that a single stem cell in every gastric gland indirectly gives rise to a clone of all differentiated cells, by production of committed progenitor cells. It is also this multipotential cell that produces new crypts by crypt fission, repairs entire crypts when damaged, and gives rise to the ulcer-associated cell lineage and gastric carcinomas. It is likely that this stem cell occupies a niche in the isthmus composed of mesenchymal cells and extracellular matrix factors, which regulates the function of the cell via mesenchymal-epithelial cross talk. The molecular events (IGF-signaling) that regulate the development of the gastric gland in the mice have begun to be understood. Ultimately, the identification of these pathways will play an important role in identifying new molecular targets for the treatment of gastric disease.

Cell Division↗

Biology and management of gastric carcinoid tumours: a review.

In recent times gastric carcinoid tumours have become the subject of substantial clinical interest as knowledge of their biological background and clinical importance has increased Gastric carcinoid tumours have long been considered rare lesions, amounting to less than 2% of all carcinoid tumours and less than 1% of all stomach neoplasms. New large databases suggest that the prevalence of gastric carcinoid is rising, with a true value now closer to 5% of all carcinoids. A tripartite classification system for gastric carcinoid tumours is now in common use: tumours associated with chronic atrophic gastritis; tumours associated with Zollinger-Ellison syndrome; and sporadic lesions. Gastric carcinoids associated with hypergastrinaemia are relatively benign, while sporadic lesions require aggressive surgical management. Gastric carcinoids, however, can be managed initially by endoscopic excision of accessible tumours, followed by regular endoscopic surveillance.

Carcinoid Tumor↗

Reconstituted botulinum type A neurotoxin: clinical efficacy after long-term freezing before use.

Botulinum neurotoxin type A (BoNT/A) is injected into muscles of facial expression for treatment of facial wrinkles. Manufacturers' recommendations state that the product should be used within 4 h of reconstitution to prevent loss of effectiveness. A prospective study was undertaken to evaluate the effectiveness of reconstituted BoNT/A when preserved in a frozen state for up to 6 months, as compared with nonfrozen BoNT/A used within 4 h after reconstitution. Treatment of 118 sites in 80 patients was performed and evaluated for aesthetic efficacy. Excellent results were observed in 94.8% of sites treated with nonfrozen BoNT/A and in 93.3% of the sites treated with frozen and thawed BoNT/A (p = 1). Minor side effects were rare and transient in both groups. In contrast to common belief, reconstituted BoNT/A may be frozen, thawed, and injected without losing its potency for up to 6 months, with efficacy equivalent to that of freshly prepared BoNT/A.

Adult↗

Gastroesophageal reflux disease: then and now.

Although Galen first described esophagitis almost 2000 years ago, its relation to acid was only recognized in the 19th century by Rokitansky. Considerably more interest in the symptoms and complications of esophagitis has been evident over the last century, as gastroesophageal reflux disease displaced peptic ulceration and became the principal acid-related disease of our times. Of particular interest has been the recognition of the clinical significance of the previously overlooked extraesophageal manifestations of the disease such as laryngitis, asthma, and sleep disturbance. The evolution of highly effective medical therapy has over the last decade drastically reduced the need for surgical intervention for control of symptoms except under select conditions, especially volume-related reflux and children with refractory symptoms. The proton pump inhibitor class of drugs is indisputably the most effective overall form of management, while individual proton pump inhibitors appear to be equivalent in their efficacy. Issues that remain to be resolved include the management of nonerosive gastroesophageal reflux disease, the long-term dependence of many patients on acid-suppressing medication, and the recognition of atypical manifestations and rare but serious complications of gastroesophageal reflux disease. In this respect, Barrett's esophagus still presents a major biologic and management conundrum for the physicians and scientists alike.

Barrett Esophagus↗