Bowel perforation during chemotherapy for non-hodgkin's lymphoma.

Bowel perforation in patients with primary malignant lymphoma usually occurs at the site of tumor. A 78 year-old man underwent chemotherapy for malignant lymphoma. He presented with abdominal pain. An emergency operation was performed under a diagnosis of panperitonitis. At laparotomy, an anal-side perforation approximately 20 cm from the Treiz ligament was observed. Drainage and partial resection of the jejunum was performed. Histopathologic examination demonstrated that there was no characteristic finding of malignant lymphoma around the perforation site in the case. Perforation of the small intestine is one of the most critical complications during the chemotherapy for malignant lymphoma. In cases of chemotherapy for malignant lymphoma, especially systemic administration, we should keep in mind the possibility of perforation of the small intestine. Fortunately, emergency surgery saved the patient presented in this report. Early diagnosis and treatment are important to improve prognosis of bowel perforation in patients with primary malignant lymphoma.

Genomic alterations in primary gastric cancers analyzed by comparative genomic hybridization and clinicopathological factors.

BACKGROUND/AIMS: Genetic changes during the oncogenesis and progression of gastric cancer remain unclear. The aim of our study was to analyze chromosomal aberrations in primary gastric cancers. METHODOLOGY: Using comparative genomic hybridization, we screened 47 primary gastric cancers for changes in the number of copies of DNA sequences. RESULTS: Gains of chromosome arms 20q (55%), 20p (36%), 17q (32%), 19q (30%) and 16p (30%), and losses of chromosome arms 4q (40%), 17p (40%), 5q (38%), 18q (30%) and 4p (28%) were detected most frequently. In addition, a high level of amplification was observed at 3q21 (2%), 6p21 (4%), 7q31 (6%), 8q23-24 (2%), 19q12-13 (2%), and 20q13 (2%). Among these alterations, the gain of 20q was the most frequent change. We then compared these changes with clinicopathological factors and identified signet ring cell carcinomas in 6 cases. Our study demonstrated no amplification of chromosome 20q in signet ring cell carcinoma in contrast to that in the other histologic types of gastric cancer. CONCLUSIONS: Our findings may be related to the morphologic and clinical features of signet ring cell carcinoma, and several oncogenes mapped on 20q may play an important role as determinants of the clinical and histologic features of gastric cancer.

Infrequent activation of mitogen-activated protein kinase in human colon cancers.

BACKGROUND/AIMS: Mitogen-activated protein kinase (MAPK) is a downstream factor of the Ras-Raf-MAPK cascade and it is now considered to be a key molecule in signaling processes stimulated by growth factors and differentiation inducers. METHODOLOGY: We examined MAPK activity in 21 advanced colon cancers to investigate whether the MAPK cascade might play a role in the progression of colon cancers. RESULTS: MAPK activation (3.9-10.1-fold) was observed in 4 of 21 cases (18%), but 3 cases (75%, 3 of 4 cases) showed MAPK activation without ras mutation, thus suggesting that MAPK activation did not correlate with the presence of Ki-ras mutations in these cases. Other kinds of oncogene activation would be involved to MAPK activation in human colon cancers. In other cases MAPK activation was not detected or partly down-regulated. CONCLUSIONS: These findings suggest that positive and negative regulation of MAPK activity are associated with loss of normal growth control and may be involved in carcinogenesis of colon cancers.

[A two-year asymptomatic case with postoperative lung metastasis of sigmoid colon cancer responding to sequential methotrexate and 5-fluorouracil].

In a 76-year-old female outpatient, recurrent lung metastasis after sigmoidectomy due to sigmoid colon cancer responded to chemotherapy of sequential methotrexate and 5-fluorouracil. A total of 46 courses of this chemotherapy in two years suppressed the rapid growth of the metastasis. During this therapy, the patient's condition was good, with no experience of nausea or leukopenia. This case suggests that chemotherapy of sequential methotrexate and 5-fluorouracil gave a person with lung metastasis of sigmoid colon cancer a good quality of life during a long time.

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of paclitaxel].

A 57-year-old woman underwent modified radical mastectomy for left breast cancer (T4bN1M1: stage IV) in September 1999. Four-cycle CAF therapy had been administered as adjuvant therapy, but multiple recurrent tumors in the liver had grown bigger and the tumor marker (CEA) increased in value. Because CAF therapy was not effective, we tried to treat the patient with systemic and intra-arterial chemotherapy using paclitaxel. The side effects of this treatment were mild nausea and appetite loss, which required no treatments. This treatment reduced the multiple liver metastases on an abdominal CT and was thought to produce a partial response (PR). The time to response was the 101st day and PR has been continued.

How safe are the xenogeneic hemostats?--Report of a case of severe systemic allergic reaction.

We report herein the unusual case of a 55-year-old woman who developed a severe systemic allergy to Avitene (microfibrillar collagen hydrochloride), a xenogeneic agent sometimes used for topical hemostasis in laparoscopic cholecystectomy. The patient developed fever, general fatigue, mild liver dysfunction, and prominent eosinophilia postoperatively. A skin allergy test confirmed that these abnormal findings were attributable to an allergic reaction to Avitene.

Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers.

Our analysis of chromosomal aberrations in primary gastric cancers using comparative genomic hybridization has revealed novel, high and frequent copy number increases in the long arm of chromosome 20, indicating that this region contains novel amplified genes involved in gastric cancer progression. AIB1, a member of the steroid receptor co-activator-1 family, has been cloned on 20q12 as a candidate target gene for this amplification in human breast cancers. In this study, we examined the numbers of AIB1 copies as well as their expression and relation to clinico-pathological features in 72 primary gastric cancers. AIB1 amplification was observed in 7% and over-expression in 40% of the specimens. AIB1 amplification always coincided with its over-expression, but several cases showed AIB1 over-expression without amplification, suggesting that expression of AIB1 is regulated not only by gene amplification but also by other mechanisms, such as transcriptional activation, in human gastric cancer. Gastric cancers with AIB1 amplification showed extensive lymph node metastases, liver metastases and poorer prognosis compared to those without amplification. Our results suggest that amplification and over-expression of AIB1 are likely to increase the number of malignant phenotypes of gastric cancers and that it can be expected to be useful as a marker of poor prognosis.

Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation.

Our recent analysis of gastric cancers using comparative genomic hybridization (CGH) revealed a novel high frequent copy number increase in the long arm of chromosome 20. Tumour-amplified kinase BTAK was recently cloned from breast cancers and mapped on 20q13 as a target gene for this amplification in human breast cancers. In the study presented here, we analysed BTAK copy-number and expression, and their relation to the ploidy pattern in 72 primary gastric cancers. Furthermore, wild-type BTAK and its deletion mutants were transfected to gastric cancers to examine changes in cell proliferation and DNA ploidy pattern. Evaluation of 72 unselected primary gastric cancers found BTAK amplification in 5% and overexpression in more than 50%. All four clinical samples with BTAK amplification showed aneuploidy and poor prognosis. Transfection of BTAK in near-diploid gastric cancers induced another aneuploid cell population. In contrast, the c-terminal-deleted mutant of BTAK induced no effect in DNA ploidy pattern and inhibited gastric cancer cell proliferation. These results suggest that BTAK may be involved in gastric cancer cell aneuploid formation, and is a candidate gene for the increase in the number of copies of the 20q, and thus may contribute to an increase in the malignant phenotype of gastric cancer.

Polymerase chain reaction for detection of carcinoembryonic antigen-expressing tumor cells on milky spots of the greater omentum in gastric cancer patients: a pilot study.

Our recent studies indicate that omental milky spots are frequently involved in the early stage of peritoneal cancer dissemination. We have used carcinoembryonic antigen (CEA)-specific RT-PCR for omental milky spots to predict peritoneal recurrence in gastric cancer patients. CEA mRNA was found to be positive in both 10 peritoneal washes and 16 greater omenta of 30 gastric cancer patients, including all 6 patients who showed positive results for both cytology and RT-PCR of peritoneal wash and omentum. Three of the 6 cases with positive RT-PCR in the greater omentum but not in the peritoneal wash showed recurrence of peritoneal carcinomatosa within 2 years after operation. Micrometastasis on omental milky spots was histologically confirmed in 6 of 30 gastric cancer cases. Non-specific band was detected only in the omentum of 1 case of 15 benign disease (7%), but not in peritoneal washes (0%), probably due to weak expression of CEA in mesothelial cells. Our results show that CEA-specific RT-PCR targeting micro-metastases on omental milky spots is more sensitive than targeting the peritoneal wash or conventional cytology, and suggest that this method is useful for the prediction of peritoneal recurrence in gastric cancer patients.

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to screen for changes in the number of DNA sequence copies in 30 primary colorectal cancers and 16 liver metastases, to identify regions that contain genes important for the development and progression of colorectal cancer. In primary colorectal cancer, we found frequent gains at 7p21 (36.7%), 7q31-36 (30%), 8q23-24 (43.0%), 12p (30%), 14q24-32 (33.3%), 16p (40.0%), 20p (33.3%), 20q (63.3%) and 21q (36.3%), while loss was often noted at 18q12-23 (36.7%). In metastatic tumors, there were significantly more gains and losses of DNA sequences than in primary tumors, with gains at 8q23-24 (found in 62.5% of recurrences vs. 43.0% of primary tumors), 15q21-26 (37.5% vs. 20.0%), 19p (43.8% vs. 20.0%) and 20q (81.3% vs. 63.3%) and losses at 18q12-23 (50.0% vs. 36.7%). The pattern of genetic changes seen in metastatic tumors, with frequent gains at 8q23-24 and 20q and loss at 18q12-23, suggests the progression of colorectal cancer. We investigated a clinical follow-up study for all patients examined by CGH and directed our attention to the genetic changes consisting of gains at 8q and 20q. The incidence of liver metastases was higher in patients with primary colorectal cancer with these genetic changes. Gains at 8q and 20q might be useful to identify patients at high risk for developing liver metastases.

Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites.

Advanced gastric cancer is often accompanied by metastasis to the peritoneum, resulting in a high mortality rate. Mechanisms involved in gastric cancer metastasis have not been fully clarified because metastasis involves multiple steps and requires a combination of altered expressions of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer peritoneal dissemination. In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumour (SNU-1) and of other cell lines established from the metastasis to the peritoneal cavity (SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB). The application of a high-density cDNA microarray method made it possible to analyse the expression of approximately 21 168 genes. Our examinations of SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB showed that 24 genes were up-regulated and 17 genes down-regulated besides expression sequence tags. The analysis revealed the following altered expression such as: (a) up-regulation of CD44 (cell adhesion), keratins 7, 8, and 14 (epitherial marker), aldehyde dehydrogenase (drug metabolism), CD9 and IP3 receptor type3 (signal transduction); (b) down-regulation of IL2 receptor gamma, IL4-Stat (immune response), p27 (cell cycle) and integrin beta4 (adhesion) in gastric cancer cells from malignant ascites. We then analysed eight gastric cancer cell lines with Northern blot and observed preferential up-regulation and down-regulation of these selected genes in cells prone to peritoneal dissemination. Reverse transcriptase-polymerase chain reaction confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination, promise to provide a new insight into the study of human gastric cancer peritoneal dissemination.