Low expression of Bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.

PURPOSE: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. EXPERIMENTAL DESIGN: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. RESULTS: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P=0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P=0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P=0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. CONCLUSIONS: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.     

Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal–cervical ratio. Ovarian volume was also significantly increased in thelarche and thelarche variant. The fundal–cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Lectin histochemical study of cholagiocarcinoma arising from stone-bearing intrahepatic bile duct

With the purpose of studying changes in the expression of glycoconjugate structures in cholangiocarcinoma and the nonneoplastic epithelium of stone-bearing intraheptic bile ducts, a panel of 12 biotinylated lectins were used on formalin-fixed, paraffin-embedded tissue sections from 13 patients who had undergone surgical resection of cholangiocarcinoma and on nonneoplastic stone-bearing intrahepatic bile ducts from 10 patients. Of the 13 patients with cholangiocarcinoma 10 had hepatolithiasis and 3 did not. Among the 12 lectins, only wheat germ agglutinin (WGA) stained the cholangiocarcinoma and nonneoplastic epithelium of the stone-bearing intrahepatic bile duct. all nonneoplastic epithelia of stone-bearing intrahepatic bile ducts were stained heavily and homogenously by WGA, the GlcNAC-specific lectin. The high columnar epithelium of both intramural and extramural glands was stained in the supranuclear region, while the low columnar epithelium of serous acini was stained in the whole cytoplasm. In the well-differentiated cholangiocarcinoma, the WGA weakly stained the neoplastic cells in the supranuclear region, while it stained the luminal cytoplasmic membrane heavily. In the poorly-differentiated chollangiocarcinoma, about 50% of cancer cells were stained with WGA. The carcinoma was moderately stained in the cytoplasm. Less reactivity and a lower percentage of cells stained with lectin were found in cholangiocarcinomas when compared to nonneoplastic epithelial. This led us to conclude that there is a dramatic decrease in lectin-binding carbohydrate structures associated with cholangiocarcinoma progression.     

Dissolution kinetics of paracetamol single crystals

The dissolution anisotropy of paracetamol crystals grown in the presence and absence of the molecularly similar additive, p-acetoxyacetanilide (PAA) was studied under controlled conditions using a single crystal dissolution method in undersaturated aqueous solutions. Linear dissolution rates were determined for all the major habit faces by measuring their movement (regression) with time in a flow cell using a microscope. The rates of dissolution of particular faces of the pure material were distinctly different in crystals of different morphology grown at different supersaturations. The dissolution rates of [001] and [110] faces of crystals grown in the presence of PAA (6.02% w/w in solution) are higher than those of pure paracetamol. The results correlate with the distribution of strain in the crystal and support the concept that integral strain increases the solubility and hence the dissolution rate of the material. The mechanism of the dissolution process at the [001], [201;] and [110] faces was defined using optical microscopy and X-ray topography. At all undersaturations above 1% the dissolution studies yielded well developed, structurally oriented, etch pits on both [001] and [201;] faces while on the [110] face rough shallow etch pits were observed. On all three faces, this etch-pitting was considerably more widespread than the dislocation content of the sector and probably reflects a 2-dimensional nucleation process rather than a dislocation controlled mechanism.     

Cryotherapeutic ablation of liver tumours

BACKGROUND: This paper reports a 7-year experience of cryoablation for colorectal and non-colorectal liver metastases. METHODS: A retrospective review was undertaken of patients treated in two adjacent UK centres in the north-west of England. RESULTS: Over a 7-year period (1993-2000), 57 patients underwent cryotherapy for malignant hepatic tumours (41 colorectal, 16 non-colorectal). In the patients with colorectal metastases, preoperative carcinoembryonic antigen (CEA) levels fell significantly, from a mean of 444.1 to 6.22 micro g/l (P = 0.002). One patient died, two developed cryoshock and six had cardiorespiratory complications. All patients with colorectal metastases subsequently received 5-fluorouracil-based chemotherapy. The remaining 16 patients with non-colorectal tumours (seven neuroendocrine metastases, five hepatocellular carcinomas, three sarcomas, one cholangiocarcinoma) all received cryotherapy alone, with no major complications. The median survival for patients with non-colorectal metastases was 37 months, compared with 22 months for those with colorectal metastases (P = 0.005). CONCLUSION: Hepatic cryotherapy is effective and safe, as demonstrated by the significant reduction in postoperative CEA concentration and the low risk of complications. However, this initial short-term success was not reflected in 5-year survival rates. Cryotherapy for non-colorectal metastases had a greater long-term survival benefit and is a useful means of controlling symptoms.     

A probability prediction rule for malignant cervical lymphadenopathy using sonography

BACKGROUND: Our purpose was to weigh various sonographic parameters as predicting malignant cervical lymphadenopathy and build a reliable prediction rule. METHODS: One hundred and eighty-nine cervical lymph node lesions from 125 consecutive patients were used for building the prediction model. Sonographic variables, including 15 morphologic features of B-mode, 5 vascular parameters of color Doppler mode, along with age and sex, were analyzed with multivariate logistic regression to evaluate the joint effect of a set of independent variables. A prediction rule for malignant lymphadenopathy was established, and prospective validation was assessed on a new group consisting of 100 lymph nodes from another 60 consecutive patients. RESULTS: The association of heterogeneous content, long transverse diameter, pathologic vascular pattern, high vascular density, and older age provided the most robust prediction value. Scoring scale was designed as 1x (age) + 2x (vascularity index) + 3x (short axis) + 4x (vascular pattern) + 4x (internal echo) according to the parameter estimates of multivariate logistic regression analysis. Cut-off value of score >==10 as malignancy resulted in 89.2% sensitivity and 85.2% specificity. Prospective validation also showed satisfactory results (sensitivity, 82.9%; specificity, 86.2%). CONCLUSIONS: By measuring only 4 sonographic parameters and age, this prediction rule could provide the physician a nonconfusing and reliable probability reference for managing cervical lymphadenopathy.