Detection of c-Ki-ras mutation by PCR/RFLP analysis and diagnosis of pancreatic adenocarcinomas.

BACKGROUND: The c-Ki-ras oncogene (also known as KRAS2) is activated by point mutations involving codon 12 in 72%-100% of primary pancreatic adenocarcinomas, but the gene is not activated in nonneoplastic tissues. Therefore, the detection of c-Ki-ras mutations can facilitate the diagnosis of pancreatic adenocarcinomas, which are not always identified with current tests. Detection is usually performed by oligonucleotide hybridization combined with polymerase chain reaction (PCR), RNAse mismatch cleavage assay, or non-isotopic mismatched PCR, methods that are not feasible for routine screening of large numbers of samples because they are time consuming and/or expensive. PURPOSE: Our purpose was to evaluate a rapid, non-radioactive method of detection of a mutation in codon 12 of the c-Ki-ras gene in pancreatic tumor samples obtained by fine-needle aspiration for diagnostic screening. METHODS: Twenty consecutive patients (15 with pancreatic adenocarcinoma, one with pancreatic cystadenocarcinoma, one with endocrine islet cell tumor, and three with chronic pancreatitis) were selected for this study. A sample of pancreatic tissue from each patient with a tumor or pancreatitis was obtained and evaluated by fine-needle aspiration biopsy under computerized tomography scan or ultrasound guidance using a two-needle coaxial technique. Pancreatic DNA from each of these samples was evaluated by PCR amplification and restriction fragment length polymorphism (RFLP) analysis with nucleotide substitution in PCR primers, creating BstNI restriction patterns that distinguished mutated from normal alleles. The accuracy of the PCR/RFLP assay was validated with DNA from SW480 and HT29 colonic carcinoma cell lines with known mutated and wild-type c-Ki-ras gene sequences. Sensitivity was tested with a series of titration experiments. RESULTS: PCR/RFLP analysis can detect a mutation present in 1% of cells. No amplification could be performed in four (20%) samples because of the absence of cells in the aspirated sample. In the 16 samples adequate for PCR/RFLP analysis, a c-Ki-ras gene mutation was detected in 11 (92%) of 12 adenocarcinomas. Overall, diagnosis was obtained by pathologic (cytomorphologic) examination alone in 13 samples (81%). The presence of malignant cells and/or mutated c-Ki-ras gene was detected in 12 of 12 adenocarcinomas but not in chronic pancreatitis or islet cell tumor. CONCLUSION: Screening of pancreatic tissue samples obtained by fine-needle aspiration for c-Ki-ras mutation using PCR/RFLP analysis combined with pathologic examination could facilitate diagnosis of pancreatic tumors.

[Digestive carcinoid tumors]. / Tumeurs carcinoïdes digestives.

Three examples of intestinal carcinoid tumours are reported. As the sign in conventional radiology are non-specific and inconstant, the computed radiographic signs are stressed. Small bowel examination showed both direct signs, intraluminal filling defects, and indirect signs with separated bowel loops, sometimes angulated and fixed. In one unusual case, all the jejunal loops were affected. On CT the specific finding was a retractile mesenteric infiltration.

Transcatheter chemoembolization of progressive carcinoid liver metastasis.

PURPOSE: The authors report their experience treating progressive liver metastases from carcinoid tumor with doxorubicin, iodized oil, and gelatin sponge embolization. MATERIALS AND METHODS: Of 23 patients, 18 had carcinoid syndrome and 19 had elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels. Relief of symptoms, changes in 5-HIAA levels, and changes in tumor size could be evaluated in 10, 11, and 17 patients, respectively. RESULTS: Symptomatic response was complete (average duration, 29 months) in 70% and partial in 30% of evaluated patients. Biologic response was complete (average duration, 21 months) in 73%, partial in 18%, and minor in 9% of evaluated patients. Morphologic response was complete in 11%, partial in 24%, and minor in 24% of evaluated patients. Survival after diagnosis of primary tumor, diagnosis of hepatic metastases, and first chemoembolization was 81, 47, and 24 months, respectively. Eight patients were alive at the end of the study. No mortality was related to chemoembolization. CONCLUSION: Chemoembolization is safe and effective for palliation of carcinoid liver metastases.

[Digestive carcinoid tumors]. / Tumeurs carcinoïdes digestives.

Three examples of intestinal carcinoid tumours are reported. As the signs in conventional radiology are non-specific and inconstant, the computed radiographic signs are stressed. Small bowel examination showed both direct signs, with intraluminal filling defects, and indirect signs with separated bowel loops, sometimes angulated and fixed. In one unusual case, all the jejunal loops were affected. On CT the specific finding was a retractile mesenteric infiltration.

[Evaluation of metastatic liver and adrenal involvement in the pre-therapeutic staging of non-small cell bronchial cancer]. / Evaluation de l'extension métastatique hépatique et surrénalienne au cours du bilan d'extension pré-thérapeutique du cancer bronchique non à petites cellules.

The evaluation of infra-diaphragmatic extension to the liver and the adrenal of non oat-cells bronchogenic carcinoma, is indicated to select the patients which may be operated. Thin slices (5 mm) on the adrenals have to be performed on the initial thoracic computed tomography, as ultrasonography (US) and MRI are less accurate. The exploration of the liver by US used as first imaging modality, may induce some false negative results, with useless surgery, and may be replaced by a CT of adrenal and liver. MRI doesn't seem actually without adapted contrast agents, significatively more efficient than CT, to detect metastases of the liver or adrenals.

Percutaneous ethanol injection for the treatment of symptomatic cystic metastases from ovarian carcinoma. Work in progress.

Two patients with symptomatic cystic metastases from ovarian epithelial carcinoma underwent ultrasound (US)-guided percutaneous aspiration and temporary injection of 99% ethanol into the cyst. In the first case, the patient initially underwent surgical resection of the mass and received systemic chemotherapy, but the cyst recurred 2 months later. Percutaneous aspiration and ethanol sclerotherapy were performed twice in the second case; fluid reaccumulated 2 months after the initial procedure. No side effects occurred. During the follow-up period (8 months in the first case and 4 months in the second), no clinical recurrence of the initial symptoms was noted. At the end of that period, a recurrent but asymptomatic cystic lesion was revealed at US examination in the first case. In the second case, a minimal asymptomatic residual collection was depicted with computed tomography. The results indicate that this technique should be considered in patients with symptomatic cystic metastases from ovarian carcinoma and may have potential benefit in the palliative treatment of such lesions.

Preoperative segmental localization of hepatic metastases: utility of three-dimensional CT during arterial portography.

To evaluate the accuracy of a fast three-dimensional (3D) reconstruction technique in determining the segmental location of hepatic metastases, 14 patients (40 metastases) were prospectively investigated before surgery with dynamic two-dimensional (2D) computed tomography during sequential arterial portography (CTAP). All patients underwent subsequent hepatic tumor resection within 4 days. After computer-generated mapping of hepatic venous structures with high attenuation and metastases with low attenuation, 3D reconstruction was performed. Thirty-six of the 40 lesions (90%) were detected with 2D and 3D CTAP. The accuracy in determining the segmental location of hepatic metastases was 78% (28 of the 36 metastases) for 2D CTAP and 94% (34 of the 36 metastases) for 3D CTAP. The difference in localization rates between 2D CTAP and 3D CTAP was statistically significant. The 3D CTAP technique provides vital data unattainable with other imaging modalities that improve the preoperative assessment of the resectability of hepatic metastases and allows planning a safer surgical approach.