Detection of sentinel lymphatic region with activated carbon particles in lymph node dissection for colorectal cancer

Sentinel node navigation surgery (SNNS) for gastrointestinal cancer has been examined using various methods, but the SN concept has not been established. For 18 patients who had colorectal cancer without macroscopic nodal metastases, we had attempted to detect sentinel lymph nodes (SNs) with activated carbon particles and investigate the existence of nodal metastases histologically. SNs were detected in 17 of 18 patients. Thus activated carbon particles are a useful tracer for SN detection. Three patients had microscopic nodal metastases, and two had nodal metastases in SNs. Although the remaining patient was a false negative case which had nodal metastases in non-SNs only, the nodal metastases were within the sentinel lymphatic region (SLR) which includes SNs. It is considered possible to safely perform minimally invasive lymphadenectomy for colorectal cancer without macroscopic nodal metastases, by means of SLR dissection using activated carbon particles.     

A case of AFP-producing gastric cancer with multiple liver metastases responding to CPT-11 and cisplatin combination chemotherapy

A case of AFP-producing gastric cancer successfully treated with CPT-11 and cisplatin combined therapy is reported together with a review of the literature. A 52-year-old male was admitted with complaints of upper abdominal pain and body weight loss. Gastric cancer with multiple liver metastases was diagnosed based on endoscopy and computed tomography findings. The patient's serum AFP level was 697,100 ng/ml and a biopsy specimen showed AFP-positive tumor cells immunohistochemically. He was treated with a combination chemotherapy consisting of CPT-11 (70 mg/m2) on day 1 and 15, and cisplatin (80 mg/m2) on day 1, repeated every 4 weeks. The primary lesion of the stomach and the liver metastases were remarkably reduced, and the serum level of AFP decreased to 18 ng/ml after 5 cycles of this treatment. No severe side effects were seen during this treatment. This result suggests that combination chemotherapy consisting of CPT-11 and cisplatin may be effective and safe for patients with AFP-producing gastric cancer with multiple liver metastases.     

Pancreatic islet cell carcinoma with multiple hepatic metastases successfully treated with a streptozocin/5-FU regimen--a case report

A 53-year-old woman was hospitalized because of lientery and steatorrhea. CT scans revealed a pancreatic head tumor along with multiple liver tumors. The pancreatic head tumor had spread to the duodenum. Following tumor biopsy with gastrointestinal fiberscopy, we diagnosed a pancreatic malignant islet cell tumor with multiple liver metastases. Since there was no clinical evidence of recognized endocrinopathy, we diagnosed "nonfunctioning" tumor. At first we administered only 5-FU at a dose of 370 mg/m2/day continuously for two weeks. However, neither the pancreatic head tumor nor the metastatic liver tumors changed in size. We then administered streptozocin and 5-FU at doses of 1,000 mg/m2 and 370 mg/m2, respectively, every week. The patient received a total of 10 g/m2 of streptozocin. After this treatment, the enlarged metastatic liver tumors were reduced in size, with marked improvement in liver enzyme. Toxic reactions to this regimen were mild. Only grade 1 nausea and alopecia were observed during the treatment. No hematological toxicity was observed, nor, with sufficient diuresis, was nephrotoxicity, demonstrating that this regimen can be administered safely.     

A case of carcinomatous enterodermal fistula successfully treated with arterial infusion chemotherapy

We report a 74-year-old male patient with a carcinomatous enterodermal fistula after residual gastrectomy, who responded to arterial infusion chemotherapy. The patient was administered 10 mg/body cisplatin (CDDP) and 1,000 mg/body 5-fluorouracil (5-FU) through an injection port every week. After 13 weeks, the fistula was closed and viable cancer cells had disappeared without any side effects. After 1 month, however, the fistula re-opened and viable cancer cells appeared again.     

Loss of Brca2 and p53 synergistically promotes genomic instability and deregulation of T-cell apoptosis

BRCA2 is a breast cancer susceptibility gene of which the product is thought to be involved in monitoring genome integrity and cell cycle progression. Brca2-null mice have a defect in embryonic cellular proliferation and die in utero. Here we report the generation of T-cell lineage-specific Brca2-deficient (tBrca2(-/-)) mice using the Cre-loxP system. Mice with a flanked by loxP allele of Brca2 were crossed to transgenic mice bearing Cre recombinase driven by the T cell-specific promoter Lck. Thymic cellularity and distribution of subset populations were normal in tBrca2(-/-) mutants. Thymocytes from tBrca2(-/-) mice underwent normal apoptosis in response to a variety of stimuli, and activated tBrca2(-/-) T cells had normal proliferative capacity. tBrca2(-/-) T cells were more likely than wild-type cells to undergo spontaneous apoptosis, but apoptosed normally in response to restimulation or DNA-damaging stress signals. Examination of metaphase spreads of tBrca2(-/-) T cells revealed that the chromosomes often exhibited aberrations such as breaks and tri-radial structures. The level of chromosomal abnormalities was enhanced in T cells from tBrca2(-/-); p53(-/-) double-mutant mice. However, tBrca2(-/-); p53(-/-) T cells did not show the enhanced level of spontaneous apoptosis demonstrated by tBrca2(-/-) T cells, a difference that likely accounts for an increase in cell number and (3)[H]thymidine incorporation of double-mutant T cells in culture compared with either single mutant. Despite this increased T-cell number, the onset of T-cell lymphomas was only marginally accelerated in tBrca2(-/-); p53(-/-) mice compared with p53(-/-) mice. Our results support a role for Brca2 in repairing spontaneous DNA lesions, and suggest that loss of Brca2 enhances the susceptibility of mouse T-lineage cells to chromosomal aberrations and deregulation of apoptosis in the absence of p53.     

Overexpression of beta 1,4N-acetylgalactosaminyl- transferase mRNA as a molecular marker for various types of cancers

OBJECTIVE: To determine GalNAcT mRNA expression in human carcinoma cell lines and primary tumor tissues. Assessment of the potential use of GalNAcT mRNA as a molecular marker for detection of metastatic cancer cells in the peripheral blood of patients with hepatocellular carcinoma. METHODS/RESULTS: We investigated GalNAcT mRNA expression in various human cancer cell lines and primary cancer tissues using RT-PCR assay for GalNAcT mRNA. The expression of GalNAcT mRNA was detected in 25 of 26 cancer cell lines tested and in the majority of primary tumors from different organs: 8 of 10 colon cancers, 9 of 9 breast cancers, 11 of 12 esophageal cancers, 14 of 14 gastric cancers, 4 of 18 pancreatic cancers, 6 of 12 biliary tract cancers, 17 of 18 hepatocellular carcinomas and 13 of 14 lung cancers. Semi-quantitative analysis with duplex RT-PCR showed that the amount of the GalNAcT mRNA was enhanced in cancer tissues as compared to the surrounding cancer-free tissues. Blood specimens of 5 of 14 patients with hepatocellular carcinoma were positive for GalNAcT mRNA, all of whom developed recurrent disease in less than 24 months. Peripheral blood samples of 30 normal subjects were negative for GalNAcT mRNA. CONCLUSION: Our results suggest that the RT-PCR assay for GalNAcT mRNA could be a potentially useful molecular marker for detecting cancer dissemination in blood circulation of patients with malignancy.     

Association between aldehyde dehydrogenase gene polymorphisms and the phenomenon of field cancerization in patients with head and neck cancer

Patients with squamous-cell carcinoma in the head and neck (HNSCC) often develop second primary esophageal squamous-cell carcinomas (ESCC). In addition, widespread epithelial oncogenic alterations are also frequently observed in the esophagus and can be made visible as multiple Lugol-voiding lesions (multiple LVL) by Lugol chromoendoscopy. Multiple occurrences of neoplastic change in the upper aerodigestive tract have been explained by the concept of 'field cancerization', usually associated with repeated exposure to carcinogens such as alcohol and cigarette smoke. However, the etiology of second ESCC in HNSCC patients remains unclear and acetaldehyde, the first metabolite of ethanol, has been implicated as the ultimate carcinogen in alcohol-related carcinogenesis. We first investigated the relation between second ESCC and multiple LVL in 78 HNSCC patients. Multiple LVL and second ESCC were observed in 29 (37%) and 21 (27%) patients, respectively. All of the second ESCC were accompanied by multiple LVL. This may indicate that episodes of multiple LVL are precursors for second ESCC. We then examined the association of multiple LVL with the patients' characteristics, including genetic polymorphisms of the alcohol metabolizing enzymes, alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2). We also investigated acetaldehyde concentrations in the breath of 52 of the 78 patients. All the patients with multiple LVL were both drinkers and smokers. Multivariable logistic analysis showed that the inactive ALDH2 allele (ALDH2-2) was the strongest contributing factor for the development of multiple LVL (odds ratio 17.6; 95% confidence intervals 4.7-65.3). After alcohol ingestion, acetaldehyde in the breath was elevated to a significantly higher level in all patients with the ALDH2-2 allele than in those without it. The high levels of breath acetaldehyde were significantly modified by the slow-metabolizing ADH3-2 allele. These results reveal strong evidence for a gene-environmental interaction between the ALDH2-2 allele and alcohol consumption, for the risk of developing multiple LVL, resulting in the development of second ESCC in patients with HNSCC. Ultimately, increased local acetaldehyde exposure thus appears to be a critical determinant of the phenomenon of 'field cancerization'.     

Colocalization of CA19-9 and KL-6 to epithelial cells in dilated bronchioles in a patient with idiopathic pulmonary fibrosis complicated by diffuse alveolar damage

A 73-year-old woman with idiopathic pulmonary fibrosis (IPF) had an elevated serum CA19-9 level, but not KL-6. Her condition worsened and she subsequently died and this was associated with a rise in the serum KL-6 level. At autopsy, the lung showed a honeycomb appearance macroscopically and, microscopically, hyaline membrane formation was seen. Immunohistochemical staining revealed partial colocalization of KL-6 and CA19-9 to dilated bronchiolar cells. These features suggest that the mechanisms that cause the synthesis and release of CA19-9 and KL-6 from damaged lung tissue in IPF are likely to differ from those in diffuse alveolar damage. In addition, serum KL-6 levels may reflect the severity of disease more sensitively than CA19-9 levels.     

Electrical connection between left superior and inferior pulmonary veins in a patient with paroxysmal atrial fibrillation

We report the case of a patient with paroxysmal atrial fibrillation, who underwent pulmonary vein (PV) electrical isolation from the left atrium (LA). Prior to achieving isolation of the left superior PV (LSPV) from the LA, earlier PV potentials were recorded inside the left inferior PV (LIPV) than LA activity during pacing at the distal LSPV. The LSPV finally was isolated by radiofrequency applications at the ostium of the LIPV. The patient had electrical connection between the LSPV and LIPV, and required radiofrequency ablation of the breakthroughs from the LA to LIPV for complete isolation of the LSPV.