Esophageal carcinoma in Southern Thailand.

BACKGROUND: Southern Thailand is an area with a high frequency of esophageal carcinoma. This paper presents basic data regarding esophageal carcinoma patients from this region. METHODS: Patients with histopathological confirmed esophageal carcinoma were retrospectively reviewed. The age, sex, location of tumor and resectability were studied. RESULTS: A total of 813 cases of esophageal carcinoma were reviewed, male:female ratio was 3.54:1 (634:179). Average age in males was 64.62 years and 64.30 years in females. The peak age-incidence was 51-70 years. Squamous cell carcinoma was most commonly found in the mid thoracic portion of the esophagus with 369 cases (45.39%), 70 cases (8.61%) were found in the cervical portion of the esophagus. Adenocarcinoma cancer was found at the esophagogastric junction in 47 cases (5.78%). Only 293 cases (36.04%) were operable. Respiratory tract involvement was noted in 49 cases. CONCLUSION: The most common type of esophageal cancer in Southern Thailand is squamous cell carcinoma, as in other countries in Asia. The status of the patients, advanced age and locally advanced tumor were major factors of our low operable rate.

TP53 mutations and MDM2 gene amplification in squamous-cell carcinomas of the esophagus in south Thailand.

Squamous-cell carcinoma of the esophagus (SCCE) shows geographic variations in incidence that are thought to reflect the etiological involvement of environmental or dietary risk factors. Mutations of TP53 are frequent in SCCE, and there is evidence that both the frequency and type of these mutations may differ from one geographic area to the other. Although SCCE is relatively rare in most parts of Thailand, the province of Songkhla (south Thailand) has been described as a high-risk area for SCCE. We have analyzed 56 SCCE cases from this area for TP53 mutations by denaturing gradient gel electrophoresis (DGGE, exons 5-8) and direct DNA sequencing. The same tumors were also analyzed for MDM2 gene amplification by differential PCR. TP53 mutations were detected in 23 cases (41%). In contrast, clear amplification of MDM2 was detected in only 2 cases (4%), both of which contained wild-type TP53. Comparison with published results from other geographic areas of high SCCE incidence revealed that the spectrum of TP53 mutations in south Thailand is similar to that observed in central China (Henan Province) but clearly differs from that of SCCE from western Europe (Normandy, France; northern Italy), with more G:T transversions and fewer mutations affecting A and T base pairs. These results suggest that SCCE from south Thailand and from central China may involve similar risk factors.

Alterations of p53, pRb, cyclin D(1) and cdk4 in human oral and pharyngeal squamous cell carcinomas.

Alteration of expression of tumour suppressor genes and cell cycle regulators may be responsible for oral and pharyngeal cancer development. We have studied the expression of p53, pRb, cyclin D(1) and cdk4 in 53 cases of oral and pharyngeal squamous cell carcinomas using immunohistochemistry. Tumour expression of all nuclear proteins was scored according to the percentage of positive cancer nuclei. Positive p53 expression was detected in 27/53 (50.94%) cases. Lack of pRb immunostaining was observed in 39/53 (73.58%) cases. Overexpression of cyclin D(1) was shown in 21 (39.62%) tumours. The overexpression of cdk4 was detected in 43/53 (81.13%) cases. There was no significant association among these cell cycle regulatory proteins. This implies that the aberration of an important cell cycle regulator may be sufficient to disrupt regulatory mechanism in a manner favouring tumourigenesis. In summary, our results suggest that inappropriate expression of p53, pRb, cyclin D(1) or cdk4 is likely to contribute to the development of oral and pharyngeal cancers. The lack of pRb expression and/or overexpression of cdk4 play a crucial role in the development of this malignancy.

Flow cytometry in squamous cell esophageal cancer and precancerous lesions.

Flow cytometry has also been used to study the nuclear DNA content (ploidy) and cell cycle kinetics of esophageal cancers. Studies of limited numbers of patients with Barrett's esophagus undergoing endoscopic surveillance suggested that aneuploidy may be a useful marker to identify subsets of patients at increased risk for malignancy. Few studies to date have evaluated premalignant tissues associated with the development of squamous-cell cancer of the esophagus. The present retrospective study comprises 80 surgical specimens of squamous-cell carcinoma of the esophagus from a high-incidence region of Thailand. All patients had surgery at the Department of Surgery, Prince of Songkla University, between March 1983 and December 1993. Sets of serial sections were cut every 0.5 cm starting from the proximal margin and down to the distal margin, and histopathology was confirmed to flow cytometric parameters (DNA content, S-phase fraction). Aneuploidy was found in 84% of squamous-cell carcinoma, 22.2% of carcinoma in situ, 28.6% of severe dysplasia, 11.0% of moderate dysplasia and 0% of mild dysplasia and normal esophageal mucosa specimens. The percentage was higher according to the level of severity or dysplasia. S-phase fraction was found to be 21.0 +/- 0.9% in squamous-cell carcinoma, 20.3 +/- 10.3% of carcinoma in situ, 20.9 +/- 5.3% of severe dysplasia, 12.9 +/- 9.7% of moderate dysplasia 7.6 +/- 0.8% of mild dysplasia and 8.9 +/- 3.2% of normal tissue. Similarly, the percentage of S-phase fraction tends to be higher according to the level of severity or dysplasia. These findings demonstrate that the aneuploidy and percentage of S-phase fraction tend to correlate with progression of esophageal premalignant tissues to invasive carcinoma. These measures may be clinically useful to identify patients at increased risk for esophageal malignancy.

Prognostic value of DNA index, S-phase fraction and p53 protein accumulation after surgical resection of esophageal squamous-cell carcinomas in Thailand.

The prognostic value of cell nuclear DNA content, S-phase fraction and p53 protein accumulation in esophageal squamous-cell carcinomas was studied in a consecutive series of 80 patients from a high-incidence region of southern Thailand, who underwent esophagectomy between 1983 and 1993. Flow cytometry was used to determine tumor ploidy, DNA index and S-phase fraction, while p53 protein accumulation was evaluated immunohistochemically using the monoclonal anti-p53 antibody, CO7. Biomarkers were correlated with clinico-pathologic findings and survival by univariate and multivariate analysis. p53 protein was found in 40 tumors (50%), and was associated with significantly reduced overall survival. In patients with immunopositive tumors, depth of primary tumor invasion, lymph-node status. TNM stage and tumor grade were also significant prognostic factors. Additional predictors of reduced overall survival after esophagectomy, determined by flow cytometry, included S-phase fraction above 10%, aneuploidy (DNA index 1.2-1.8) and multiploidy (DNA index > 2.2). This study further implicates p53 in the pathogenesis of esophageal squamous-cell carcinoma. Prognostic factors such as p53 protein, S-phase fraction and DNA index may be useful in stratifying patients for adjuvant therapies in future clinical trials of esophageal cancer.

Experience with oesophageal carcinoma in Songklanagarind Hospital.

Clinical data from 175 patients with squamous cell carcinoma of the oesophagus or cardia admitted to Songklanagarind Hospital between 1982 and 1988 were analysed to evaluate the effects on survival of various tumour and treatment variables. Most tumours (greater than = 86%) were in stage III or IV. Forty-seven percent of stage-IV tumours and 99 per cent of those in stages I, II or III were resectable. One-year and 3-year survival rates of resected stage-III patients (57.3% and 27.5%) were significantly higher than those of resected stage-IV patients (33.3% and 0%). Resection conferred no benefit over radiotherapy chemotherapy or no treatment on the survival of stage-IV cases beyond one year. Combined chemotherapy/radiotherapy/resection of stage-III and stage-IV patients gave no statistically significant improvement in survival. Among resected patients, only lymph node involvement was associated with significantly lower survival (relative risk compared to no involvement = 2.3, 95% CL: 1.2, 4.6), while the fungating type of tumour was possibly associated with improved survival (relative risk compared with all other types = 0.24, 95% CL: 0.05, 1.1).

Surveillance of oesophageal carcinoma in southern Thailand in 1988.

The lower subregion of the south of Thailand has an overall higher incidence and mortality associated with oesophageal cancer than does the upper subregion. The increased incidence in the lower south is more marked among females than among males, but the male/female incidence ratio in the lower subregion is still high (3.7:1). There is evidence also of an increased incidence in the eastern provinces compared with that in western provinces. Available data on occupation and district of residence provide no clues to the cause of the distinct geographic pattern of incidence within the southern region.

Early detection of oesophageal carcinoma in southern Thailand.

The use of balloon cytology technique for detection of oesophageal carcinoma has been tested in 73 non-symptomatic patients and 53 patients with symptoms of oesophageal carcinoma from the high incidence of Southern Thailand. Cytological findings were compared with findings of esophagoscopy and oesophageal biopsy. Among symptomatic patients, scope/biopsy revealed 29 positive for carcinoma, against which balloon cytology yielded 9 false negatives (sensitivity 69%), but no false positives. All false negatives were of the stenosing type of tumour. One of 3 early cases of carcinoma revealed by the balloon technique among asymptomatic patients could not be detected by oesophagoscopy, biopsy or oesophagogram, but was confirmed by repeated cytological examination. The basic properties of the balloon cytology technique appear to justify its use as a routine diagnostic tool among high-risk patients for oesophageal carcinoma in Southern Thailand.

Solitary rectal ulcer. Electron microscopy study of two cases.

Two cases of solitary rectal ulcer syndrome occurred in an 18-year-old woman and a 24-year-old man. Each had a history of bleeding on defecation, together with constipation alternating with diarrhea. In each case, a solitary rectal ulcer was noted by sigmoidoscopy and confirmed by both light and electron microscopic evaluations of biopsy material. Both clinical and pathologic features of these cases are compatible with classic rectal ulcer syndrome, which has been suggested to result from trauma followed by an ischemic event leading to fibrosis of the mucosa. Fibrosis in these two cases was confirmed by electron microscopy.