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Biomedical subjects

S Law

Publications and source records attributed to S Law.

At least 19 recordsLinked to original sources

Pharyngolaryngoesophagectomy using the thoracoscopic approach.

BACKGROUND: Thoracoscopic mobilization of the esophagus for pharyngolaryngoesophagectomy allows dissection under direct vision, and therefore it potentially results in fewer complications than conventional transhiatal mobilization. In this article we report our experience with this approach. It was also hypothesized that a learning curve existed and that results have improved over time. PATIENTS AND METHODS: From July 1994 until January 2004, 57 patients underwent pharyngolaryngoesophagectomy in our institution. Intraoperative events and postoperative outcome were prospectively documented, and long-term follow-up data were also studied. Results were compared between the first 30 patients and the last 27 patients. RESULTS: There were no significant differences between the two groups with respect to the various clinicopathological characteristics. There was no difference in the median thoracoscopic time between the first 30 and last 27 patients at 90 and 75 min, respectively, p = 0.18. For the complete procedure there was significantly less blood loss in the later group; median (range) blood loss 700 (164-3000) ml versus 400 (100-1200) ml, p = 0.002. Overall pulmonary complications occurred in 12 patients (40%) in the first group versus 13 (48%) in the second group, p = 0.6. The incidence of atrial arrhythmia was also similar, affecting 6 (20%) patients and 3 (11%), respectively, p = 0.47. Hospital mortality rates were 13.3% and 7.4%, p = 0.67. Two-year survival rates were no different (46% versus 45% p = 0.85). CONCLUSIONS: Although, subjectively, operating skills have improved over time, better results in the second half of this series could not be demonstrated clearly, likely because the operating surgeons had prior extensive experience in esophageal and thoracoscopic procedures.

Adult↗

A plastic scintillation dosimeter for high dose rate brachytherapy.

In vivo dose verification in brachytherapy requires a small insertable dosimeter with a real-time readout capability. Fibre optic scintillation dosimeters, consisting of a plastic scintillator coupled to an optical fibre, are one of the most promising dosimeters for this application. We have developed two sizes of the BrachyFOD scintillation dosimeter which have external diameters of 2.2 mm and 1 mm and have determined their important dosimetric characteristics (depth dose relation, angular dependence, temperature dependence, energy dependence). We have shown that the background signal created by Cerenkov and fibre fluorescence does not significantly affect the performance in most clinical geometries using an (192)Ir source from an HDR brachytherapy unit. The dosimeter design enables readout at less than 0.5 s intervals. The BrachyFOD satisfies the need for a real-time in vivo brachytherapy dosimeter.

Brachytherapy↗

Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9.

A gene critical to esophageal cancer has been identified. Functional studies using microcell-mediated chromosome transfer of intact and truncated donor chromosomes 3 into an esophageal cancer cell line and nude mouse tumorigenicity assays were used to identify a 1.61 Mb tumor suppressive critical region (CR) mapping to chromosome 3p14.2. This CR is bounded by D3S1600 and D3S1285 microsatellite markers. One candidate tumor suppressor gene, ADAMTS9, maps to this CR. Further studies showed normal expression levels of this gene in tumor-suppressed microcell hybrids, levels that were much higher than observed in the recipient cells. Complete loss or downregulation of ADAMTS9 gene expression was found in 15 out of 16 esophageal carcinoma cell lines. Promoter hypermethylation was detected in the cell lines that do not express this gene. Re-expression of ADAMTS9 was observed after demethylation drug treatment, confirming that hypermethylation is involved in gene downregulation. Downregulation of ADAMTS9 was also found in 43.5 and 47.6% of primary esophageal tumor tissues from Hong Kong and from the high-risk region of Henan, respectively. Thus, this study identifies and provides functional evidence for a CR associated with tumor suppression on 3p14.2 and provides the first evidence that ADAMTS9, mapping to this region, may contribute to esophageal cancer development.

ADAM Proteins↗

Esophageal hematoma.

Hematoma of the esophagus is an uncommon condition. Patients often present with acute odynophagia or retrosternal pain, which may be confused with other diagnoses. We report herein two patients with esophageal hematoma caused by foreign body ingestion. Conservative treatment resulted in complete resolution. The literature is reviewed for the etiology, clinical features and management of this condition.

Aged↗

Clinical relevance of Fas expression in oesophageal squamous cell carcinoma.

AIMS: To determine the extent of Fas expression in oesophageal squamous cell carcinomas (ESCCs) from Chinese patients and to correlate Fas expression with clinicopathological prognostic parameters. METHODS: Clinicopathological data were collected from 58 patients with ESCC who underwent oesophagectomy and had no prior radiotherapy or chemotherapy. Immunostaining was performed on the primary tumours. Expression of Fas was correlated with patients' demographics, tumour characteristics and stage, R category of surgery, and patients' survival. RESULTS: The actuarial survival rates of all patients at two and five years after surgery were 48% and 14%, respectively. Fas expression was detected in 89.7% of ESCCs. Higher Fas expression recorded on a four point scale correlated with better tumour differentiation (p < 0.01), but not with other patient or tumour variables. Importantly, higher Fas expression was associated with better survival (p = 0.0317). CONCLUSIONS: These findings suggest that Fas activated apoptosis is important in the pathogenesis of ESCC. This molecular pathway may be a potential therapeutic target for ESCC.

Adult↗

Spontaneous pneumomediastinum in a scuba diver.

Pneumomediastinum usually occurs following an airleak from the lungs, or from a perforated oesophagus. We report on a 30-year-old man who developed pneumomediastinum after scuba diving. The patient presented with acute onset of throat pain, odynophagia, and hoarseness of voice. The literature is reviewed for this condition.

Adult↗

Management of spontaneous perforation of esophageal cancer with covered self expanding metallic stents.

Optimal management of esophageal perforation is controversial, especially in the presence of malignancy. Esophagectomy has traditionally been employed for patients with malignant perforations. However, in patients with advanced disease, other less invasive treatment options may be of benefit. We present two cases of spontaneous perforation of advanced esophageal cancer successfully managed by insertion of covered self-expanding metallic stents and a review of the literature.

Aged↗

Esophageal atresia and achalasialike esophageal dysmotility.

A 14-year-old boy presented with regurgitation, malnutrition, and chronic lung insufficiency with a history of successful repair of esophageal atresia and tracheoesophageal fistula in the newborn period. Barium swallow and manometry results showed achalasia. Hellar operation with antireflux procedure resulted in complete symptomatic relief. Histology and immunohistochemistry including PGP9.5, MAP5, cKit, and nNOS of myotomy specimen showed intact innervation. Although esophageal dysmotility after esophageal atresia repair usually is caused by gastroesophageal reflux and incoordination of peristalsis, the possibility of achalasia should also be considered, because a casual relationship between esophageal atresia and achalasia may exist.

Adolescent↗

Low prevalence of incidentally discovered and early-stage esophageal cancers in a 30-year autopsy study.

Autopsy studies provide information that may guide future patient management. This study analyzed autopsy findings in patients with esophageal cancers, with emphasis on the prevalence of incidentally diagnosed esophageal cancer, histologic subtypes, early-stage lesions, and any associated pathology. Autopsies detected 346 patients (306 men; 40 women) with esophageal carcinomas during a 30-year period, constituting an overall prevalence of 3.4%. Out of these patients, 30 (8.7%) were incidentally discovered at autopsy. Squamous cell cancers were found in 336 (97.1%) patients, small cell cancers in nine (2.7%), and adenocarcinomas in one (0.3%). Stage distributions were stage I in seven patients (2%), stage II in 49 (14%), stage III in 121 (35%), and stage IV in 169 (49%). Isolated dysplasia or carcinoma-in-situ were not found. Comparing with symptomatic patients, patients with incidental cancers were older, had higher frequency of small cell carcinomas, and lower T-stage. The prevalence of incidentally diagnosed esophageal carcinomas and early-stage carcinomas were low. Unusual histologic subtypes may be found.

Adult↗

Pluripotent bone marrow cells in leukemic mice elicit enhanced immune reactivity following sheep erythrocyte administration in-vivo. A possible S-LFA3 interactive immunotherapy.

Reports concerning the compartmentwise immunoreactivity and migratory property of the bone marrow derived stem/progenitor cells have been poorly documented. The present study shows that both in normal and leukemic mice a low density group of bone marrow cells (LDC) are functionally less matured than a high density group of cells (HDC) as revealed from spontaneous E-rosetting, cytotoxic efficacy and phagocytic function against the targets which correlated well with the migratory activity of the cells from LDC to HDC compartment. This is deranged in leukaemic groups of animals. Administration of Sheep Erythrocytes (SRBC) significantly increased the CD34+ cell population as evident through flowcytometric (FACS) analysis and the above immune reactivity in leukemic mice. The results indicated that, (a) bone marrow cells comprising the major fractions of immature cells are capable of eliciting immune-reactivity against the targets in normal and (b) poorly in leukemic mice and that (c) sheep red blood cells could effectively trigger such immunological functions together with enhanced maturation dependent migration in leukemic mice. The study hints at therapeutic potentiality of SRBC or its determinant molecule TIITS or Sheep-leucocyte function antigen 3 (S-LFA3/CD 58) in stimulating the stem and progenitor cells in vivo.

Animals↗

Squamous cell carcinoma and adenocarcinoma of the lower third of the esophagus and gastric cardia: similarities and differences.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lower esophagus and gastric cardia were compared in their clinical features and long-term prognosis. Two hundred and ninety-five patients with SCC and 263 with ADC were reviewed. Resectability rates for SCC and ADC were 74.2% and 73.2% respectively (P=0.8). Among those who underwent resection, ADC was more advanced, with 22.3% at stage IV compared with 7.4% for SCC (P=0.001). Postoperative cardiac events occurred in 24.2% of SCC patients and 14.7% of ADC patients (P=0.015), and major respiratory complications in 20.1% and 8.6% respectively (P=0.001). Thirty-day mortality rates were 2.7% and 4% (P=0.46), and hospital mortality rates were 11.4% and 7.6% (P=0.19). Median survival rates were 12.5 months for SCC and 11.6 months for ADC (P=0.99) and 5-year survival rates were 19.9% and 17.6% (P=0.55) respectively. Squamous cell carcinoma of the lower esophagus and ADC of the cardia differed in patient demographics and clinical features but long-term prognoses were similar.

Adenocarcinoma↗

Facilitation of functional compartmentalization of bone marrow cells in leukemic mice by biological response modifiers: an immunotherapeutic approach.

Biological Response Modifiers (BRMs) including interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and sheep erythrocytes (SRBC) protected N,N'-ethylnitrosourea (ENU) induced leukaemic mice. Two cell types from the bone marrow were isolated in density specific gradient representing two distinct compartments, the low density cells being more CD34 positive than the high density group. Investigations with the functional efficacy of such compartments revealed significant improvement of cytotoxic efficacy and phagocytic burst at the high density compartment (HDC) level. The high density compartment was found to be more responsive towards the BRMs compared to the cells of the low density compartment (LDC). It was suggested that use of BRMs in vivo can stimulate a potent functional progenitor compartmentalization in normal as well as leukaemic mice. These observations are expected to help a logistic approach towards combined BRM therapy at the clinical level.

Animals↗

Esophageal blue nevus: an isolated endoscopic finding.

BACKGROUND: The occurrence of blue nevus has seldom been reported in extracutaneous sites and with no record in the esophagus. CASE REPORT: A blue nevus was reported in the esophagus of a 58-year-old Chinese woman. On endoscopic examination, the lesion presented as linear patches of bluish pigmentation in the esophagus. The patient was free of symptoms 3 years after the endoscopic examination. CONCLUSIONS: We believe this represents the first reported case of blue nevus in the esophagus. The clinicopathologic features, differential diagnoses, and the nature of the lesion are discussed, along with a review of the literature.

Esophageal Diseases↗

Oesophageal basaloid squamous cell carcinoma: a unique clinicopathological entity with telomerase activity as a prognostic indicator.

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.

Adult↗

What is appropriate treatment for carcinoma of the thoracic esophagus?

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?

Adenocarcinoma↗

Critical appraisal of the significance of intrathoracic anastomotic leakage after esophagectomy for cancer.

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.

Anastomosis, Surgical↗

Assembly of microarrays for genome-wide measurement of DNA copy number.

We have assembled arrays of approximately 2,400 BAC clones for measurement of DNA copy number across the human genome. The arrays provide precise measurement (s.d. of log2 ratios=0.05-0.10) in cell lines and clinical material, so that we can reliably detect and quantify high-level amplifications and single-copy alterations in diploid, polyploid and heterogeneous backgrounds.

Aneuploidy↗

Two-field dissection is enough for esophageal cancer.

Three-field lymphadenectomy for esophageal cancer remains controversial. The high prevalence of cervical lymph node involvement is the basis of cervical lymphadenectomy. Studies of recurrence patterns after esophagectomy, however, indicate that clinically relevant cervical nodal recurrence is uncommon, and that the incidence of such recurrence is similar to that of two-field lymphadenectomy. Moreover, a convincing survival benefit cannot be proven for the more extended lymphadenectomy. The emphasis of three-field lymphadenectomy has shifted to lymphadenectomy of the superior mediastinum and along the recurrent laryngeal nerve chains. Radical dissection of these areas may improve local disease control; the price to pay is increased postoperative morbidity and impaired long-term quality of life. Furthermore, the selection of appropriate patients for extended lymphadenectomy is difficult. Formal three-field lymphadenectomy seems unnecessary, but the controversy of the optimal extent of lymphadenectomy and its impact on survival remains unanswered.

Adenocarcinoma↗