Concealment of medication in patients' food.
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Biomedical subjects
Publications and source records attributed to J Wong.
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PURPOSE: Angiogenesis, a process fundamental to tumor growth, is regulated by angiogenic factors. This article reviews prognostic and other clinical implications of circulating angiogenic factors in cancer patients. METHODS: A MEDLINE search of literature was performed using the names of various angiogenic factors as the key words. Studies pertaining to circulating angiogenic factors in cancer patients were reviewed. Pertinent literature regarding tumor expression of common angiogenic factors and their prognostic relevance in human cancers were also examined. RESULTS: A substantial number of studies have demonstrated a strong association between elevated tumor expression of vascular endothelial growth factor (VEGF) and advanced disease or poor prognosis in various cancers. This supports the pivotal role of VEGF in regulating tumor angiogenesis. More recently, there is mounting evidence that the level of circulating VEGF in patients with different types of cancer may be predictive of tumor status and prognosis. Preliminary data also suggest that circulating VEGF may be useful in predicting and monitoring tumor response to anticancer therapies and in follow-up surveillance for tumor relapse. There are reports supporting the prognostic value of other circulating angiogenic factors such as basic fibroblast growth factor, platelet-derived endothelial cell growth factor, transforming growth factor-beta, and angiogenin, but their clinical significance is less conclusive because of limited data. CONCLUSION: Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.
A new human esophageal cancer cell line, named SLMT-1, was established from a nude-mouse xenograft of a well-differentiated esophageal squamous cell carcinoma (ESCC) of the lower esophagus from a male Hong Kong Chinese patient. SLMT-1, passaged over 34 times and with a doubling time of 31 hours, has the microscopic features of epithelial cells with adherent growth as a monolayer. The general biologic properties of SLMT-1 cells were characterized by (1) a positive test of tumorigenicity obtained by injecting cells subcutaneously into athymic nude mice and observing their development into well-differentiated squamous cell carcinoma; (2) immunohistochemical staining using antibodies (AE1/AE3, CAM5.2 and MAK 6) which show the presence of cytokeratin intermediate filaments; and (3) electron microscopy demonstrating the morphologic features of epithelial cells with the presence of desmosomes. The cytogenetic abnormalities found in both the primary culture and SLMT-1 included der(1;14)(q10;q10), add(1)(p1?), +1, +2, del(3)(q11), +6, +7, i(8)(q10), +8, +10, +11, -13, -15, +16, +17, -18, -19, -Y and marker chromosomes. Additional changes observed in the 34th passage included gains as well as losses of both numerical and structural abnormalities. Comparative genomic hybridization (CGH) indicated copy number gains on chromosomal regions 3q32-qter, 5p, 8p12-p11.2, 11q13-q22 and 13q22-qter, and loss of the Y. The gains of 8p12-p11.2 in SLMT-1 cells are novel to ESCC. Based on its distinct and common characteristics, the SLMT-1 cell line serves as a useful tool for studying the molecular and genetic basis of the pathogenesis of ESCC.
HYPOTHESIS: The combined endoscopic and laparoscopic approach is safe and effective in managing gallstone cholangitis in the era of laparoscopic cholecystectomy (LC). DESIGN: Retrospective case series. SETTING: University teaching hospital. PATIENTS: One hundred eighty-four consecutive patients with gallstone cholangitis treated between January 1995 and December 1998. INTERVENTIONS: The main treatments were endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) followed by interval LC. Open or laparoscopic common bile duct exploration (OCBDE or LCBDE) was used when ERCP or ES failed. MAIN OUTCOME MEASURES: Success of various interventions, morbidity and mortality, and long-term incidence of recurrent biliary symptoms. RESULTS: Endoscopic retrograde cholangiopancreatography was successful in 175 patients (95%), with bile duct stones found in 147 (84%). Endoscopic stone clearance by ES was achieved in 132 patients (90%). Morbidity rate after ERCP or ES was 4.0% (n = 7), and overall mortality rate from cholangitis was 1.6% (n = 3). After bile duct stone clearance, 82 patients underwent LC with a conversion rate of 9.8% (n = 8) and a morbidity rate of 3.6% (n = 3). Eighteen patients underwent OCBDE with a morbidity rate of 33% (n = 6), and 3 underwent LCBDE with 1 conversion and no morbidity. There was no operative mortality. Seventy-eight patients were managed conservatively after endoscopic clearance of bile duct stones. Follow-up data were available in 101 patients with cholecystectomy and 73 patients with gallbladder in situ. During a median follow-up of 24 months, recurrent biliary symptoms occurred in 5.9% (n = 6) and 25% (n = 18), respectively (P =.001). In both groups, the most common recurrent symptom was cholangitis (n = 5 and n = 14, respectively). Gallbladder in situ (risk ratio, 4.16; 95% confidence interval, 1.39-12.50; P =.01) and small-size papillotomy (risk ratio, 2.94; 95% confidence interval, 1. 07-8.10; P =.04) were significant risk factors for recurrent biliary symptoms. CONCLUSIONS: Endoscopic sphincterotomy for biliary drainage and stone removal, followed by interval LC, is a safe and effective approach for managing gallstone cholangitis. Patients with gallbladder left in situ after ES have an increased risk of recurrent biliary symptoms. Laparoscopic cholecystectomy should be recommended after endoscopic management of cholangitis except in patients with prohibitive surgical risk.33333333333333333333333
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BACKGROUND: Damage to a small-for-size liver graft after reperfusion is frequently observed but the mechanism of injury remains unclear. HYPOTHESIS: Injury to a small-for-size liver graft is related to the changes of portal pressure and blood flow. MAIN OUTCOME MEASURES: Survival rates, portal hemodynamics, microcirculatory changes, and morphological changes (by light microscopy and electron microscopy). SETTING: A rat model of nonarterialized orthotopic liver transplantation comparing 2 groups of rats transplanted with whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of recipient liver weight). RESULTS: Median survival of the rats with small-for-size grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after reperfusion, mean arterial pressure of the small-for-size graft group was significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm Hg, P =.04; 15-minute: 96 vs 127 mm Hg, P =.04). Portal pressure (in centimeters of water) of the small-for-size graft group was significantly higher in the first 20 minutes after reperfusion than the level before the anhepatic phase (5-minute: 15.1 vs 9.3, P =.02; 10-minute: 16.1 vs 9.3, P =.03; 15-minute, 13.5 vs 9.3, P =.03; 20-minute: 13.4 vs 9.3, P =.03) and was significantly higher than that of the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1 vs 9.6, P =.02; 10-minute: 16.1 vs 10.3, P =.04). Hepatic microcirculatory blood flow (in milliliters per minute per 100 g) was also significantly higher in the small-for-size graft group during the first 40 minutes after reperfusion (5-minute: 16.3 vs 9.3, P =.02; 10-minute: 14.9 vs 6.6, P =.02; 15-minute: 14.8 vs 5.5, P =.02; 20-minute: 13.1 vs 7.0, P =.02; 30-minute: 13.2 vs 8.8, P =.04; 40-minute: 14.6 vs 7.1, P =.02). Light and electron microscopy showed normal morphological features of whole graft up to 24 hours after reperfusion. The small-for-size graft, however, showed sinusoidal congestion, tremendous swelling of mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and collapse of the space of Disse. CONCLUSIONS: In a rat model, the portal hemodynamic changes in small-for-size grafts are transient. Progressive damage of the graft may result from microcirculatory failure due to irreversible endothelial injury after reperfusion.
HYPOTHESIS: Hepatic resection improves quality of life (QOL) in patients with resectable hepatocellular carcinoma (HCC). DESIGN: A prospective longitudinal study. SETTING: A university teaching hospital. PATIENTS: Sixty-six consecutive patients undergoing resection of HCC, and 10 patients with unresectable HCC found after surgical exploration who were subsequently treated with transarterial chemoembolization (control group). MAIN OUTCOME MEASURE: Serial measurements of preoperative and postoperative QOL using the Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire for up to 2 years after surgery (at 3, 6, 9, 12, 18, and 24 months). RESULTS: Among the 66 patients with resectable HCC, the mean postoperative QOL scores at 3 months after surgery were significantly higher than the mean preoperative QOL scores in domains related to physical, social, and emotional well-being and relationship with physicians. The mean total QOL score increased from 83.5 (SD, 9.4) before surgery to 94.1 (SD, 7.7) at 3 months after surgery (P <.001). No significant change of QOL scores at 3 months after surgery was observed in the control group. Twenty patients in the resected group died of early recurrence within 2 years after surgery, but their mean postoperative QOL scores remained higher than the preoperative QOL scores for most assessment times. In contrast, in the control group, the mean total QOL scores became significantly lower than the preoperative scores, starting 9 months after surgery. Forty-six patients in the resected group completed all QOL assessments. At all postoperative assessments, their mean QOL scores were higher than preoperative scores. Recurrence developed in 13 of the 46 patients within the 2-year study, and there was significant deterioration of QOL over time among these 13 (P <.001), whereas no significant change in QOL over time was observed among the 33 recurrence-free patients. Of various clinicopathologic factors, only advanced pTNM stage was significantly predictive of deterioration of QOL over time after resection of HCC. CONCLUSIONS: Hepatic resection results in significant enhancement of QOL in patients with HCC. Development of recurrence is the main factor leading to deterioration in QOL over time after resection of HCC.
Oesophageal basaloid squamous cell carcinoma (BSCC) is uncommon and has been reported to have a worse prognosis than squamous cell carcinomas (SCCs), but this tumour has not been fully characterized. The aim of the present study was to analyse the clinicopathological features of a large cohort of patients with oesophageal BSCC treated at a single institution. The pathology of 756 primary oesophageal cancers treated between January 1989 and December 1998 was reviewed. Tumours that fulfilled the diagnostic criteria of BSCC were identified and were compared with SCC. Their expression of MIB-1, DNA ploidy, and telomerase activity were also studied. Thirty Chinese patients (25 men and five women) with BSCC were found, comprising 4% of patients with oesophageal cancer treated by surgical resection in the study period. Their median age was 67 years (range 40-78 years). Dysphagia was usually the main presenting symptom. Other concomitant malignant tumours were seen in three patients and paraneoplastic glomerulopathy in one. Five tumours were located in the upper third, 19 in the middle third, and six in the lower third. The median length was 5.8 cm (range 2-12 cm). The median MIB-1 score of BSCC was 750 (range 400-858) and was higher than that of SCC (p=0.003). The primary tumour and metastatic BSCC were aneuploid, as detected by flow cytometric analysis in nine patients. Telomerase activity was positive in 95% (19 out of 20) of the cases analysed. The 5-year survival of patients with BSCC was 12%. Distant metastases were seen in 53% (n=16); lung and liver were the most common sites. The median survival of patients with tumours which had a high level of telomerase activity was significantly shorter than those with low levels of telomerase activity (1 vs. 27 months) (p=0.001). The median survival of patients with BSCC and SCC was 26 and 16 months, respectively (p=0.3). In conclusion, BSCC has distinctive clinicopathological features and its long-term prognosis is no worse than SCC. The level of telomerase activity may have a prognostic role.
BACKGROUND: Little is known about the cellular defects and molecular mechanisms leading to pancreatic endocrine tumors (PETs). p27(Kip1) is a universal cyclin-dependent kinase inhibitor (CDKI), which acts as a tumor suppressor and a negative regulator of cell cycle. From previous reports, quiescent cells show high levels of p27(Kip1) expression while neoplastic and proliferating cells show no detectable p27(Kip1) expression. We hypothesize that in malignant sporadic PETs, p27(Kip1) expression would be decreased compared with benign PETs and normal pancreatic tissue. METHODS: Western analysis was performed on 28 PETs (7 malignant, 21 benign), 2 nonendocrine cell lines, and 5 endocrine cell lines. Signal intensities were quantitated using densitometry and standardized to normal pancreas. RESULTS: Unexpectedly, increased p27(Kip1) expression as compared with control was seen in both benign and malignant tumors, as well as in all four pancreatic islet tumor cell lines, but not fibroblast or pituitary cell lines, evaluated. There was no difference in p27(Kip1) level between benign and malignant tumors. CONCLUSION: This represents the first report of anomalous p27(Kip1) overexpression in sporadic PETs, and is part of a growing literature describing the paradoxical overexpression of p27(Kip1) in human tumors that includes other endocrine tumors. These studies suggest a unique molecular pathway leading to endocrine tumorigenesis.
PURPOSE: We compared the recovery profiles, postoperative complications, perioperative OR utilization times, and times to discharge of patients undergoing ambulatory knee arthroscopy under spinal anesthesia (SA) or general anesthesia (GA). METHODS: In this randomized, prospective study, 84 ASA I-II patients were randomized to receive either SA with 50 mg of 1% lidocaine, or a standardized GA. Postoperative pain, nausea and vomiting, sedation, OR utilization, postanesthesia care unit (PACU), and ambulatory surgical unit (ASU) recovery were compared. RESULTS: Patients in the GA group had more pain in the PACU than the SA group (61% vs 15%, P <0.01), and a higher incidence of PACU analgesic use (59% vs 7.5%, P <0.01). Patients in the SA group were able to drink and eat sooner than the GA group (83 +/- 23 vs 95 +/- 22 min, P <0.05 and 88 +/- 27 vs 105 +/- 29 min, P <0.01, respectively). The times to sit, walk, and void were similar. The length of PACU and ASU stay between the GA and SA groups were similar (67 +/- 17 vs 60 +/- 19 min, P >0.05 and 122 +/- 27 vs 127.9 +/- 31 min, P >0.05, respectively). The incidence of backache was higher in the SA group (35 vs 13.6%, P <0.05) than the GA group. However, the incidence of sore throat was higher in the GA compared to the SA group (25% vs 2.5%, P <0.01). CONCLUSIONS: SA with 50 mg of 1% lidocaine provides an improved recovery profile for ambulatory knee arthroscopy. Discharge times were similar, and with the exception of backache and sore throat, the incidence of complications was similar.
Recent advances in the treatment of esophageal cancer have yielded a variety of new options for management of this highly lethal disease. Various approaches to surgical resection have been proposed. Chemotherapy and radiotherapy with or without surgery have been tested in numerous trials, the results of which are often conflicting and confusing for clinicians. The changing epidemiology of the disease between East and West adds to the controversy. In this review, the authors address some of the more controversial debates. The following questions are asked: What is the appropriate approach for surgical resection? What is the appropriate extent of resection? Is multimodality treatment appropriate for esophageal cancer?
BACKGROUND: The effects of increased intra-abdominal pressure in various organ systems have been noted over the past century. The concept of abdominal compartment syndrome has gained more attention in both trauma and general surgery in the last decade. This article reviews the current understanding and management of intra-abdominal hypertension and abdominal compartment syndrome. METHODS: Relevant information was gathered from a Medline search of the English literature, previous review and original articles, references cited in papers, and by checking the latest issues of appropriate journals. RESULTS AND CONCLUSION: Akin to compartment syndrome in extremities, the pathophysiological effects of increased intra-abdominal pressure developed well before any clinical evidence of compartment syndrome. These effects include cardiovascular, pulmonary, renal and intracranial derangement, reduction of intestinal and hepatic blood flow, and reduction of abdominal wall compliance. Although abdominal compartment syndrome is more commonly noted in patients with abdominal trauma, it is now evident that non-trauma surgical patients could also develop the condition. Early initiation of treatment for intra-abdominal hypertension is currently advocated in view of the possibility of subclinical progress to the full-blown abdominal compartment syndrome.
BACKGROUND: Leakage from esophageal anastomoses is higher than that for other gastrointestinal anastomoses. An intrathoracic anastomotic leak is a potentially catastrophic event. METHODS: Patients with and without thoracic anastomotic leakage were compared for predisposing factors. Leak-related mortality was analyzed. RESULTS: Of 475 patients, there were 17 leaks (3.5%). Predisposing technical factors occurred significantly more frequently in patients who leaked. Sixteen such events were identified as contributory in 11 patients. The hospital mortality for patients who leaked was significantly higher (35% versus 9%, P = 0.005). Inadequate drainage and persistent sepsis accounted for 4 of the 6 deaths. The need for inotropic support postoperatively correlated with leak-related mortality (66% versus 0%, P = 0.006), while leak size, time to diagnosis, or method of drainage did not. CONCLUSIONS: Thoracic anastomotic leaks are largely preventable. Leak-related mortality for the series was 1% and was most commonly related to inadequate drainage.
BACKGROUND: Basic fibroblast growth factor (bFGF) is an important positive regulator of tumor angiogenesis. This study evaluated the role of serum bFGF as a biological marker of tumor invasiveness and postresection recurrence in hepatocellular carcinoma (HCC). METHODS: Concentrations of bFGF in preoperative serum samples in 88 patients undergoing resection of HCC were measured by a quantitative enzyme-linked immunosorbent assay. A single pathologist performed histopathologic examination of all tumor specimens. All patients were prospectively monitored for tumor recurrence. RESULTS: The preoperative serum bFGF levels ranged from <0.22 to 71.2 pg/mL (median 10.8 pg/mL). There was significant correlation between high serum bFGF levels and large tumor >5 cm, presence of venous invasion or advanced pTNM stage. Patients with a serum bFGF level >10.8 pg/mL had worse disease-free survival than those with a level <10.8 pg/mL (median disease-free survival 11.2 versus 20 months, P = 0.044). Serum bFGF level >10.8 pg/mL (P = 0.035) and tumor size >5 cm (P = 0.004) were independent preoperative factors that predicted early recurrence after resection of HCC. CONCLUSIONS: This study supports a role of bFGF in tumor growth and invasion in HCC. A high preoperative serum bFGF level appears to be predictive of invasive tumor and early postoperative recurrence. The clinical implications of serum bFGF level in HCC warrant further investigation.
OBJECTIVE: To describe a new disease-specific questionnaire with established measurement properties that addresses the dimensions of health-related quality of life considered important to women with endometriosis. METHODS: The Endometriosis Health Profile-30 was developed in three stages. Stage 1 included open-ended exploratory interviews with 25 women to generate the items on the questionnaire. Stage 2 was an 87-item questionnaire administered in a postal survey to identify the most salient dimensions of health-related quality of life. In stage 3, the reliability and validity of the questionnaire were evaluated. RESULTS: The final instrument contained a core questionnaire with 30 items and five scales: pain, control and powerlessness, emotional well-being, social support, and self-image. Six modular parts consisting of 23 questions were also developed and measured the areas of sexual intercourse, work, relationship with children, feelings about the medical profession, treatment, and infertility. All the scales achieved high internal reliability, with Cronbach's alpha coefficient ranging from 0.83 to 0.93 (core questionnaire) and 0.79 to 0.96 (modules). The intraclass correlation coefficients to evaluate the test-retest reliability were high (range 0.88-0.98, P <.001). Content validity was demonstrated as the questionnaire was developed from interviews of patients rather than existing literature and clinical scales. Construct validity was assessed by correlating the Endometriosis Health Profile-30 scales with the relevant Short Form-36 scales. High correlations for all comparisons were found (-0.41 to -0.73). CONCLUSION: The Endometriosis Health Profile-30 is a reliable, valid, patient-generated instrument to measure the health-related quality of life of women with endometriosis. Its application in various health care settings will provide new and valuable information on the effect of endometriosis on health-related quality of life from the patients' perspective.
An egg-that took weeks to months to make in the adult-can be extraordinarily transformed within minutes during its fertilization. This review will focus on the molecular biology of the specialized secretory vesicles of fertilization, the cortical granules. We will discuss their role in the fertilization process, their contents, how they are made, and the molecular mechanisms that regulate their secretion at fertilization. This population of secretory vesicles has inherent interest for our understanding of the fertilization process. In addition, they have import because they enhance our understanding of the basic processes of secretory vesicle construction and regulation, since oocytes across species utilize this vesicle type. Here, we examine diverse animals in a comparative approach to help us understand how these vesicles function throughout phylogeny and to establish conserved themes of function.
PURPOSE: To determine the early and midterm results of femoro-popliteal angioplasty with adjunctive stenting and to identify factors affecting early and continuing success. METHODS: Sixty-nine consecutive balloon angioplasty procedures on the superficial femoral artery (SFA) were performed in 60 limbs and 55 patients in the operating theater. Fifty-two percent of lesions were occlusions, and 87% involved the distal half or the whole segment of the SFA. Immediate endovascular stenting was used in all procedures, involving the placement of 105 stents, with a mean stented length of 13.8 cm. Twenty-nine procedures (43%) were performed for critical ischemia. Three-monthly duplex ultrasound was used for follow up assessment, with stenosis of > 50% defined as the endpoint for failure. The patient demographic and biochemical data, and procedural details were correlated with success criteria according to Society of Vascular Surgery standards. RESULTS: Initial technical success by intent to treat was 92%, with four procedure-related complications and no deaths. Initial success by anatomic, hemodynamic and clinical criteria were 98.3, 96.7 and 93.3% respectively (92.2, 90.6 and 87.5% by intent to treat). Cumulative primary patency at 6, 12, and 24 months was 73.1, 62.6 and 53.8%, and secondary patency 84.9, 72.1 and 72.1% correspondingly. Significant factors relating to inferior patency were occlusions, stented segment length > 10 cm, procedure in claudicants, and the use of the Memotherm stent. CONCLUSIONS: Angioplasty and stenting of the superficial femoral artery has acceptable primary and secondary patency rates even in the presence of long stenosis and occlusions. A duplex surveillance program is recommended for early detection and timely treatment of restenosis.
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