Overexpressed fibroblast growth factor receptor 2 in the invasive front of colorectal cancer: a potential therapeutic target in colorectal cancer.

Fibroblast growth factor receptor 2 (FGFR2) is considered a novel therapeutic target for various cancer. We used a silencing strategy to clarify the effect of reduced FGFR2 expression in human colorectal cancer (CRC) cells. The invasive front of cancer cells exhibited stronger FGFR2 expression than the surface area of the cancers. FGFR2 shRNA-transfected LoVo cells inhibited cell migration, invasion and tumor growth in vitro and in vivo. Thus, FGFR2 plays important roles in CRC progression in association with tumor cell migration, invasion and growth, and FGFR2 might be a novel therapeutic target for CRC.

Determination of the minimal essential serum folate concentration for reduced risk of colorectal adenoma.

BACKGROUND & AIMS: There are no data regarding basal folate levels in patients without colorectal adenoma. This study aimed to determine the minimum serum folate concentration that associates with reduced risk of colorectal adenoma. METHODS: 1510 consecutive patients underwent total colonoscopy for suspected colorectal lesions after barium enema examination. Prior to colonoscopy, history of alcohol consumption was noted and blood serum analyzed for folate and vitamin B12 levels. Polypoid lesions were evaluated histologically. We excluded patients with anemia, history of colonoscopy, overconsumption of alcohol, or malignancies. In all, 458/1510 patients (male/female; 258/200, 40-75 years) were determined eligible. Variables were compared between patients with adenoma and those without adenoma. RESULTS: Serum folate concentration was the variable with the most significant statistical variation between males with adenoma (8.0 ng/ml) and males without adenoma (9.2) (p = 0.001). Serum folate concentrations in females with adenoma did not differ significantly from those in females without adenoma (10.7 versus 10.9). When subjects were stratified into groups according to serum folate, we found no significant difference in the prevalence of adenoma in patients with folate levels greater than 8.0 ng/ml. CONCLUSION: Patients with serum folate concentrations above 8.0 ng/ml had the lowest risk of developing colorectal adenoma.

Determining best potential predictor during high-dose progestin therapy for early staged and well-differentiated endometrial adenocarcinoma using semiquantitative analysis based on image processing and immunohistochemistry.

This study aimed to examine whether morphological changes during the early stage of treatment or indices of proliferation, apoptosis, or hormone receptors are reliable predictors of the hormonal response to uterus-preserving high-dose progestin therapy in patients with endometrial adenocarcinoma. Seven patients (5 good responders and 2 poor responders) with presumptive stage IA endometrial adenocarcinoma treated with 600 mg/day of medroxyprogesterone acetate were reviewed. Epithelial cell size and stromal area observable on microscopic examination of hematoxylin and eosin-stained sections, and immunostaining labeling indices for Ki-67 nuclear antigen, single-stranded DNA, estrogen receptor, and progesterone receptor were semiquantitatively analyzed before treatment and after 4, 8, 12, and 16 weeks of treatment using computer imaging programs. The mean ratio of cell size after 4 weeks of treatment to that before treatment in good responders was 3.83, whereas the ratios in the 2 poor responders were 1.08 and 0.98. The mean Ki-67 nuclear antigen labeling index before treatment was 37.2% for the 5 good responders but was 51.0% in the 2 poor responders. The indices of the poor responders remained high (20%-77%), even after 16 weeks of treatment; in contrast, the indices of the good responders were low (0.4%-7.3%) throughout the treatment period. No definitive differences in labeling indices for single-stranded DNA, estrogen receptor, or progesterone receptor were observed between good and poor responders or at different stages of treatment (p>0.05). In conclusion, a higher epithelial cell size ratio after 4 weeks of treatment in conjunction with lower Ki-67 nuclear antigen labeling indices could be a potential predictor of hormonal response.

A case of tumor lysis syndrome following chemotherapy for a uterine epithelioid leiomyosarcoma with focal rhabdomyosarcomatous differentiation.

Tumor lysis syndrome (TLS) is a potential complication characterized by hyperuricemia, hyperphosphatemia, hyperkalemia and hypocalcemia due to massive necrosis of malignant cells after cytotoxic therapy. This fatal complication occurs frequently in tumors with hematological malignancies, such as acute lymphoblastic leukemia and Burkitt's lymphoma, and in other tumors with high proliferative rates and tumor burdens. TLS is rarely associated with the treatment of solid tumors. Herein, we report a case of TLS following the initial administration of effective chemotherapy for an epithelioid leiomyosarcoma with focal rhabdomyosarcomatous differentiation of the uterus.

A case of extrahepatic bile duct wall recurrence of gastric carcinoma that was treated with pancreaticoduodenectomy.

We report on a patient with obstructive jaundice caused by recurrence of gastric carcinoma in the wall of an extrahepatic bile duct more than 5 years after gastrectomy who was treated with pancreaticoduodenectomy. Histopathologic examination of the surgically resected specimen revealed a poorly differentiated adenocarcinoma with focal signet ring cells in the wall of the common bile duct which was histologically similar to the primary gastric carcinoma. To confirm the diagnosis, immunohistochemical staining was performed with antibodies against cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC5AC, MUC6, MUC2). Based on the expression patterns of this monoclonal antibody panel, the final diagnosis of the common bile duct tumor was an isolated local recurrence of the gastric carcinoma. The patient has survived for more than 26 months after pancreaticoduodenectomy without recurrence.

Venous hemangioma of the anterior mediastinum.

We report a rare case of venous hemangioma (VH) of the anterior mediastinum in a 56-year-old man admitted to our hospital because of hematemesis. Systemic examinations were performed and chest computer tomography (CT) revealed a 1.5-cm sized small nodule with contrast enhancement in the thymus. Both CT and magnetic resonance imaging (MRI) suggested a solid tumor such as a thymoma or neurogenic tumor rather than a vascular neoplasm. A partial thymectomy including this nodule by video-assisted thoracic surgery (VATS) was performed. Histological examination showed VH. There was no recurrence with no further treatment.

A true pulmonary carcinosarcoma that required diagnostic differentiation from a pleomorphic adenoma: a case report.

Pulmonary carcinosarcoma is a rarely encountered tumor. We treated a patient who had an intrabronchial polypoid lesion that required a diagnostic differentiation from epithelial-mesenchymal mixed neoplasms inclusive of pleomorphic adenoma, and that was diagnosed by immunohistochemical staining to be a true carcinosarcoma. A 69-year-old man underwent left pneumonectomy in November 2000 with a diagnosis of atelectasis resulting from a tumor obstructing the left lower lobar bronchus, and also a lung abscess. The tumor was initially diagnosed as pleomorphic adenoma, since it contained both benign-looking epithelial and mesenchymal elements, but immunohistochemical staining demonstrated myoglobin-positive rhabdomyosarcomatous elements along with cytokeratin-positive squamous cell carcinoma elements. A definite diagnosis of pulmonary carcinosarcoma was confirmed.

Case of meningeal carcinomatosis with gastric cancer which manifested meningeal signs as the initial symptom; the palliative benefit of radiotherapy.

A 53-year-old male presenting with anorexia, intermittent diplopia, general fatigue, headache and vertigo was admitted to our hospital. He was diagnosed as having gastric cancer by endoscopy of his upper gastrointestinal tract. Brain computed tomography (CT) showed no abnormalities, but magnetic resonance imaging (MRI) showed slight enhancement in the cerebellar sulcus. Cytological examination of cerebrospinal fluid revealed malignant cells. He became blind one week after hospitalization. We diagnosed his condition as meningeal carcinomatosis (MC) and started radiotherapy. His vision improved after four weeks of treatment, and then he became totally blind again. Since his general condition remained poor, we did not perform chemotherapy. He died on the 127th day of hospitalization. MC is a rare pathosis of gastric cancer in comparison with leukemia and malignant lymphoma. This disease does not often show characteristic pictorial images, and early diagnosis is difficult. Moreover, it usually manifests itself in its late stages after several months or more of treatment, and it is rare for MC to be present at the time of initial diagnosis. We present a case of gastric cancer with meningeal signs present when the primary tumors were diagnosed. Radiotherapy alleviated some of the symptoms, and the patient survived for as long as patients undergoing enforced chemotherapy.

Case of adenosquamous carcinoma of the ascending colon.

Adenocarcinoma accounts for most of the malignant tumors originating from the colon, whereas adenosquamous carcinoma is rare, accounting for about 0.1% of all colon cancers. We present herein a case of adenosquamous carcinoma of the ascending colon. The patient was a 94-year-old woman who presented with a chief complaint of lower abdominal pain. A barium enema examination and lower gastrointestinal endoscopy showed a type 3 tumor in the ascending colon, and a biopsy confirmed the diagnosis of adenosquamous carcinoma. Right hemicolectomy was performed, and the tumor was diagnosed as a stage III advanced colon cancer. The patient had postoperative aspiration pneumonia and died 35 days after surgery. A search of Japanese literature over the past 25 years yielded 70 patients with adenosquamous carcinoma of the colon, and the clinicopathological features are discussed herein.

Male choriocarcinoma with metastasis to the jejunum: a case report and review of the literature.

We report on a patient with male choriocarcinoma. The patient was a 31-year-old male patient with jejunal choriocarcinoma that metastasized from the mediastinum. He was admitted complaining of melena and severe anemia. Upper and lower gastrointestinal endosocopy was performed, but no source of bleeding was seen. Chest X-ray and CT revealed a mediastinal tumor 7 cm in size anterior to the arotic arch. Superior mesenteric arteriography showed irregularities and macular opacity in the jejunal artery. An emergency laparatomy was performed because of massive gastrointestinal bleeding. A jejunal tumor approximately 4 cm in size was resected and numerous metastases were observed in the liver and mesentery. Histopathological examination showed metastatic jejunal choriocarcinoma. Gynecomastia was not present and the testes were normal. Serum beta-human chorionic gonadotropin (HCG) was at an abnormally high level of 4,396 ng/mL. Because of metastases to the brain and invasion to the trachea, he died on postoperative day 20. We report this rare case of a male patient with metastases of choriocarcinoma to the gastrointestinal tract from the mediastinum, together with a review of the literature.

Correlation between clinical pathologic factors and activity of 5-FU-metabolizing enzymes in colorectal cancer.

INTRODUCTION: Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) are initial key enzymes in the 5-fluorouracil (5-FU) metabolic pathway. The expression levels and activities of these three enzymes play important roles in the response of cancer patients to 5-FU-based chemotherapy. PURPOSE: The purpose of this study was to investigate the relationship between the activities of 5-FU metabolic enzymes and clinicopathologic factors in colorectal cancer. METHODS: We measured the activities of OPRT, DPD, and TS in colorectal cancer tissues. We also investigated the correlations between the activities of these three enzymes and clinicopathologic factors (histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, and vascular invasion). We examined 100 patients with surgically resected colorectal cancer. RESULTS: Poorly differentiated adenocarcinoma showed significantly higher DPD activities than did moderately differentiated or well-differentiated adenocarcinoma. In patients with lymph-node metastasis, OPRT activity was significantly lower than in patients without lymph-node metastasis. No significant relation was found between TS activity and histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, or vascular invasion. CONCLUSION: The response to 5-FU may be poor in patients with lymph-node metastasis, because of low OPRT activity, and in patients with poorly differentiated adenocarcinoma, because of high DPD activity.

[Antitumor effect of paclitaxel for gastric cancer is AUC dependent].

Paclitaxel (PTX), which is used for ovarian cancer, lung cancer, breast cancer and gastric cancer, is administered at a dose of 210 mg/m(2) once every three weeks. However, WHO grade 3-4 hematological and non-hematological toxicity occurred frequently in this manner. In recent studies about ovarian cancer and lung cancer, a schedule in which PTX was given weekly could have the same or better efficacy, with fewer side effects. The response rate of PTX administered every three weeks for gastric cancer, was 23.3 to approximately 28.0%, while that of PTX administered weekly was 24.0 to approximately 25.8%. Because of fewer adverse events, weekly PTX is widely used for gastric cancer in Japan. To prove the validity of PTX weekly administration, we performed a study using six specimens removed surgically and one specimen collected from ascites. A chemosensitivity test was performed on the basis of two assumptions: a high concentration for a short time, and a low concentration for a long time. A similar PTX effect was obtained when the AUC was equal. In this study, we demonstrated that the effect of low-dose PTX was equal to the effect of high-dose PTX in gastric cancer.

Complete response of a patient with advanced gastric cancer, showing Epstein-Barr virus infection, to preoperative chemotherapy with S-1 and cisplatin.

Here we report the case of a patient with advanced gastric cancer with esophageal invasion who was treated with chemotherapy using S-1 and cisplatin (CDDP) preoperatively. The patient was a 72-year-old woman who was diagnosed with advanced gastric cancer (T3N2M0) with esophageal invasion. S-1 was orally administered at 80 mg/day (60 mg/m(2) per day) on days 1-14 and CDDP was infused at 80 mg/day (60 mg/m(2) per day) on day 8, followed by a 1-week rest. Marked reductions in the sizes of the primary tumor and metastatic lymph nodes around the stomach were observed after two cycles of the therapy. Adverse reactions occurring during the therapy were only grade 2 gastrointestinal disorder and grade 1 leukocytopenia. Radiological and endoscopic examinations before surgery showed that a partial response (PR) had been achieved. The patient underwent curative surgery consisting of total gastrectomy, D2 lymph node dissection, and splenectomy. Her postoperative course was uneventful, without surgical complications. No gastric cancer cells were detected in the primary lesion or lymph nodes by immunohistochemical staining with cytokeratin, confirming a histological complete response (CR). As Epstein-Barr virus-encoded small RNA (EBER) had been detected by in-situ hybridization in the gastric cancer cells of a biopsy specimen, this tumor was diagnosed as an Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which was effectively treated with S-1 and cisplatin chemotherapy.

A case of multiple gastric carcinoids that could not be preoperatively diagnosed.

Here, we report the case of patient with multiple gastric carcinoids showing histopathological behavior similar to that of type I carcinoid tumors of the stomach. The patient was a 61-year-old man diagnosed as having a gastric tumor, which was revealed by follow-up computed tomography. Upper gastrointestinal endoscopy revealed a protruded tumor in the greater curvature and a small polyp in the anterior wall of the upper stomach. A biopsy revealed gastric carcinoid. Because he refused to be operated for gastric carcinoid, upper gastrointestinal endoscopy was performed 5 months later. A malignant transformation of the gastric carcinoid was strongly suspected. Therefore, the patient was admitted for operation. Laboratory findings were normal. With the diagnosis of type III gastric carcinoid, total gastrectomy was performed. Microscopic examination revealed that the carcinoid tumor was confined to the submucosa and that the small polyp mentioned earlier was also a carcinoid. Microcarcinoids and numerous enterochromaffin-like cell hyperplasias were observed along the muscularis propria of the fundus. The tumor differed from typical type I gastric carcinoids in several ways. Immunohistochemical staining for chromogranin A, synaptophysin, and cytokeratin was positive. However, p53 was absent, and the MIB-1 index was low. Two years after surgery, the patient is alive without recurrence.

Angiogenic switching in the alveolar capillaries in primary lung adenocarcinoma and squamous cell carcinoma.

The status of angiogenic switching was examined in alveolar capillaries of primary lung adenocarcinoma (ADC) from 10 patients and primary squamous cell carcinoma (SCC) from 11 patients, using immunostaining for CD31, thrombomodulin, von Willebrand factor (vWF), collagen types IV and VII, and alpha-smooth muscle actin (alpha-SMA). We applied the TdT-mediated dUTP nick-end labeling assay and the reverse transcription-polymerase chain reaction for vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). In bronchioloalveolar and papillary subtypes of ADC, the neoplastic cells, replacing the normal alveolar epithelial cells, had spread over alveolar walls and adhered firmly to alveolar interstitium as shown by the development of type IV collagen. Neoplastic cells of SCC were characterized by local proliferation in alveolar sacs without firm attachment to alveolar walls. Tumor lesions of SCC had often developed necrotic foci of various size. In ADC and SCC, alveolar capillary endothelial cells newly obtained reactivity to vWF. Such segments of endothelial cells lost surface thrombomodulin expression. CD31 was consistently expressed in normal and ADC tissues, but each endothelial cell marker was often attenuated or even lost in SCC, suggesting degeneration or necrosis of the alveolar capillaries. The capillary pericytes and interstitial fibroblasts were often hypertrophic and developed alpha-SMA in the cytoplasm in ADC, but they became atrophic in SCC. In ADC, apoptosis occurred in cells of alveolar capillaries more frequently in the peripheral zone than in the deeper zone of the tumor, whereas the frequency was not consistent in SCC. In microdissected alveolar wall tissues, mRNA expression patterns of VEGF isoforms and VEGFRs were similar in both ADC and SCC. In ADC, de novo angiogenic switching took place in cytoplasm as a unit of cells segments in alveolar capillary endothelium. Suppression of angiogenic switching in SCC implies that factors other than VEGF-VEGFR interaction, such as physical contact and compression of tumor cells, might play a critical role in alveolar capillaries.

Metastatic thoracic lymph node carcinoma of unknown origin on which we performed two kinds of immunohistochemical examinations.

Metastatic cancers of the thoracic lymph nodes without primary sites are rare. Such cancers are difficult for clinicians to manage as identifying the primary sites is difficult in using routine histologic examinations alone. We searched for the site of the primary lesion using immunohistochemical exploration of cytokeratin (CK) and thyroid transcription factors 1 (TTF-1), and 2-[18F] and fluorodeoxyglucose positron emission tomography (FDG PET) in a patient with cancer of the hilar lymph node without any known primary site. To our knowledge, there are no previous similar reports. A 45-year-old man presenting with a tumor in the right hilar region, underwent surgical resection of the tumor, resulting in a diagnosis of metastatic cancer of the bronchopulmonary lymph nodes. An immunohistochemical examination revealed the neoplastic lesion to be positive for CK7, negative for CK20, and negative for TTF-1. Repeated searches to identify the site of the primary lesion by FDG PET over the 35 months since operation have failed to locate a primary site.

Mucinous carcinoma identified as lung metastasis from an early rectal cancer with submucosal invasion by immunohistochemical detection of villin.

We encountered a male patient aged 64 with pulmonary mucinous carcinoma in whom a diagnosis of pulmonary metastasis from early rectal cancer with submucosal invasion was made based on an immunohistochemical examination. A rectal cancer was detected together with a mass in the lung. The mass in the lung was consistent with mucinous adenocarcinoma, whereas the invasion of rectal cancer was confined to the submucosa; thus, distant metastases appeared unlikely. These lesions were assessed using immunohistochemical staining for cytokeratin and thyroid transcription factor-1, which failed to make a definite diagnosis. A further assessment was made by staining for villin. Both neoplasms were positive for this protein, demonstrating a common brush-border pattern. A lung metastasis from rectal cancer with submucosal invasion was diagnosed. Villin is considered useful for detecting primary neoplastic lesions based not only on its specificity but also on its staining pattern, which is different from that of other proteins.