- [Show abstract] [Hide abstract] ABSTRACT: Most inverted Meckel's diverticulums responsible for adult intussusception have rich fat tissues which are located interior to the wall and which may act as a disease lead point. This association provides the possibility for accurate preoperative diagnosis using a characteristic feature observable with CT MPR (Multiplanar Reconstruction). We report the case referred to our hospital of a 39 year-old female who had experienced one month of intermittent abdominal pain, nausea, and vomiting. Abdominal plain X-P showed niveau while CT MPR revealed the same low density area to be fat tissue in the lead point of the intussusceptum, a proximal segment of the bowel. A circular isodensity area outside this area indicated the wall of the diverticulum. We diagnosed diverticulum rather than lipoma as the cause of the patient's ileus. Manual reduction as part of an emergency operation for ileo-ileo intussusception was successfully performed and the diverticulum as the lead point located 100 cm from an ileocecal valve was resected. Pathological results revealed that the intussusception was caused by a Meckel's diverticulum with rich fat tissue.
- [Show abstract] [Hide abstract] ABSTRACT: The feasibility and efficacy of adriamycin or epirubicin in combination with cyclophosphamide followed by weekly paclitaxel (AC/EC-weekly PAC) as adjuvant chemotherapy for breast cancer was investigated. Node-positive breast cancer was treated with AC/ EC-weekly PAC, namely AC at 60/600 mg/m(2) or EC at 90/600 mg/m(2) x4 at three-week intervals, followed by weekly PAC (80 mg/m(2)) x 12, namely four cycles of single weekly administration for three weeks followed by a one-week rest (3 x 4 PAC) or single weekly administration for 12 consecutive weeks (12 PAC). One hundred and three of 109 consecutive patients enrolled were analyzed, of whom 96 (93.2%) completed the regimen. Grade 3/4 neutropenia occurred in 52.4% receiving AC/EC, and 10.9% of 55 receiving 12 PAC but only 2.1% of 48 receiving 3 x 4 PAC. Neuropathy disorders occurred in more than half receiving PAC, which did not improve after one-week rest in 3 x 4 PAC. AC/EC-weekly PAC is feasible and without serious complications.
- [Show abstract] [Hide abstract] ABSTRACT: Preclinical studies have shown that irinotecan (CPT-11) and cisplatin (CDDP) can act synergistically. Several chemotherapy regimens combining CPT-11 and CDDP for advanced gastric cancer have been reported to demonstrate high response rates and high incidence of severe toxicity. We conducted a combination chemotherapy regimen of low-dose CDDP and CPT-11 to prolong the time to progression with less toxicity. Seven patients with histologically-confirmed intestinal type of gastric adenocarcinoma were enrolled in this study. All patients were male, and their age at diagnosis ranged from 52 to 76 with a mean age of 64.8. Six patients received combination chemotherapy with CPT-11 and CDDP after the gastrectomy (stage I b: 1, II : 3, III b: 1, IV: 1). Only chemotherapy was administered in one patient because of a far advanced primary lesion and metastatic tumors. Low-dose CDDP (20 mg/body) and CPT-11 (65 mg/m(2)) were administered intravenously once every two weeks. The overall response rate was 43% including 1 complete response and 2 partial responses. One patient had grade 3 myelosuppression. Other adverse reactions were mild. The combination of low-dose CDDP and CPT-11 has mild therapeutic toxicities and may achieve a prolonged median survival time in patients with intestinal- type gastric adenocarcinoma.
- [Show abstract] [Hide abstract] ABSTRACT: Follow-up colonoscopy of a 25-year-old Japanese man with ulcerative colitis (UC) who had undergone endoscopic mucosal resection twice for early colon cancers revealed the presence of a new 1.5-cm-diameter tumor in the sigmoid colon. It was diagnosed by preoperative biopsy as a poorly differentiated adenocarcinoma. Sigmoidectomy was performed, and the pathological findings revealed lymphoepithelioma-like carcinoma (LEC). In situ hybridization to detect Epstein-Barr virus (EBV)-encoded small RNAs showed positive signals in stromal lymphocytes, but weak signals in the tumor cells. The association between EBV and LEC was obscure in this case. Unlike typical UC-mediated colon cancers, the lesion was poorly differentiated, and negative for p53 signals immunohistochemically. These findings may hint at a novel mechanism of carcinogenesis in UC-mediated colorectal cancer.
- [Show abstract] [Hide abstract] ABSTRACT: Fine-needle aspiration cytology (FNA) is less traumatic and technically easy to apply to small breast tumors. A total of 382 cases of palpable breast lesions that had undergone fine needle aspiration and histopathologic diagnosis were reviewed with an emphasis on the rate of false positive diagnoses in benign breast lesions. A diagnosis of " malignant " was made in 98 of the 382 specimens (25.6%). The predictive value for malignancy was 97.9%. The sensitivity, specificity, and accuracy of FNA were 86.3%, 98.2%, and 93.2%, respectively, when the " suspicious " group was considered positive for malignancy. The histologic subtypes of the 4 false-positive cases were epithelial proliferative lesions, ductal or lobular hyperplasia. None of these 4 cases were definitely diagnosed as " malignant " by radiological studies. Four false-negative cases by FNA were suspicious for malignancy radiologically. There was no specific pathological subtype associated with false-negative status on FNA in this study. Palpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.
- [Show abstract] [Hide abstract] ABSTRACT: Aim: Tumor levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) in the primary site of malignant tumors have been investigated as predictive markers for the anti-tumor efficacy of 5-FU derivatives. However, the expressions in their metastatic sites, which should be the target tissues of adjuvant setting, have not been well discussed because it is difficult to obtain the tissue. The aim of our study is to clarify the correlation of mRNA levels of TP, TS and DPD between primary tumor tissues and metastatic lymph nodes. Materials and methods: Twenty-one patients with gastric cancer who underwent gastrectomy were studied. Informed consent was obtained from all patients prior to the operations. Immediately after the gastrectomy, specimens from gastric cancer tissues, normal mucosa and perigastric lymphnodes were excised, frozen in liqN 2 and kept at -80°C. TP, DPD and TS mRNA levels were assayed by real-time RT-PCR. Results: TP, DPD and TS mRNA levels and TP/DPD in primary tumor tissues were well correlated with those in each metastatic lymph node (TP: r = 0.667, p = 0.0006, DPD: r = 0.632, p = 0.0016, TS: r = 0.585, p = 0.0045, TP/DPD: r = 0.597, p = 0.0035). Conclusion: The expression levels of biomarkers in the primary tumor tissues obtained at surgical operations might predict the efficacy of 5-FU derivatives against metastatic tissues.
- [Show abstract] [Hide abstract] ABSTRACT: Matrilysin, MMP-7, is an important target for anti-metastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis. In a previous report, we showed that matrilysin accelerated human umbilical vein endothelial cell (HUVEC) proliferation in low serum conditioned medium. In the present study, we show that matrilysin stimulation decreased VE-cadherin expression, induced accumulation of beta-catenin in the nucleus of the HUVEC, and up-regulated matrilysin mRNA expression. These results compel a hypothesis that matrilysin cleaves VE-cadherin and releases beta-catenin from the VE-cadherin/catenin complex; the free beta-catenin can activate T-cell factor (Tcf) DNA binding protein, which accelerates cell proliferation and matrilysin expression.
- [Show abstract] [Hide abstract] ABSTRACT: To examine four-node axillary sampling assisted by a blue dye (4NAS/dye) technique as a sentinel node biopsy (SNB) for breast cancer. Lymphatic mapping was performed by injection of patent blue for 33 consecutive cases with breast cancer. Axillary sampling was performed until four nodes were obtained. This was followed by back-up axillary lymph node dissection to examine the feasibility of 4NAS/dye. The same study with 30 cases was conducted at an independent hospital to confirm the feasibility of this method. This method was then applied to 101 consecutive clinically node-negative patients to avoid axillary-node dissection, with intraoperative diagnosis made by frozen section examination. The median numbers of blue-stained nodes and nodes excised by 4NAS/dye were 1.7 and 3.4, respectively. The identification rate of sentinel lymph nodes (SNs) was 81.8% using the dye alone and 97.0% when the combination was used. Pathological examination revealed that the nodal status was correctly predicted by the dye alone in 62.5% of cases with metastasis, whereas in 100% by 4NAS/dye. The dye alone was not sufficient to identify SNs, especially in cases with prior excisional biopsy. The identification rate of SNs and the accuracy rate in another feasibility study were 100% and 92.5% in 30 consecutive cases, respectively. 4NAS/dye successfully detected SNs in 100 of 101 cases of the subsequent observational study with an acceptable post-operative axillary morbidity and thus succeeded as an SNB. The 4NAS/dye method is reliable for the detection of SNs. This method could be applied to observational studies without radio-isotope.
- [Show abstract] [Hide abstract] ABSTRACT: We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group, which had the same size liver but no PL. The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays and the hepatic ATP level was measured. The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, P < 0.05). Gene expression of cyclin D1, proliferating cell nuclear antigen, cyclin A and B was upregulated, and the cyclin-dependent kinase inhibitor was downregulated. Increases were observed in: (i) pyruvate dehydrogenase, the tricarboxylic acid cycle cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48 +/- 0.01 micromol/ml vs. 0.33 +/- 0.01 micromol/ml, P < 0.05). The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism.
- [Show abstract] [Hide abstract] ABSTRACT: We assessed the utility of dynamic magnetic resonance imaging (MRI) in differentiating benign from malignant lesions of the breast and then applied MRI to diagnose intraductal breast tumors with nipple discharge. Gadolinium (Gd)-enhanced MR mammography was performed on 74 patients with breast tumors and 8 patients with nipple discharge. The steepest slopes of the contrast medium uptake (S slope) s from time-intensity curves were significantly different between malignant and benign lesions. At S slope threshold of 0.95% /second, malignancy was predicted with a sensitivity and specificity of 75% . Six of 8 cases with nipple discharge were successfully identified by MR ductography by injecting Gd-DTPA into discharging ducts. Among them, 2 non-invasive ductal carcinomas were differentiated from benign lesions by the S slope value. Dynamic MR mammography is an useful modality for differentiating breast lesions and has potential for evaluating intraductal lesions with nipple discharge.
- [Show abstract] [Hide abstract] ABSTRACT: Docetaxel is an active agent as first-line chemotherapy in patients with advanced breast cancer at a dosage of 100 mg/m2. However, the efficacy of this agent as a first-line drug when used at a lower dosage is unclear. This study was performed to evaluate the clinical efficacy and safety of 60 mg/m2 docetaxel for the treatment of breast cancer. This study enrolled 23 patients with advanced and/or metastatic breast cancer, who had not been treated with an anthracycline or taxane previously. Treatment with docetaxel was continued in patients showing a response until there was evidence of disease progression or unacceptable toxicity. Among 20 fully evaluated patients, the overall response rate was 50.0% and the median time to progression was 31 weeks. The most commonly observed adverse events were neutropenia (78.2%) and fatigue (60.9%). Fluid retention occurred in only 8.7% of the patients. Adverse events did not cause discontinuation of the treatment. Docetaxel achieved good disease control with mild adverse events in first-line treatment at a dosage of 60 mg/m2.
- [Show abstract] [Hide abstract] ABSTRACT: Bone resorption markers have become available for the diagnosis of bone metastasis. We evaluated cross-linked collagen C-and N-telopeptides (ICTP and NTx) in diagnosing bone metastasis from breast cancer. For a threshold of 4.5 ng/ml of 1CTP and 55.0 pmol BCE/micromol of NTx, bone metastasis could be predicted with an accuracy of 84% and 63%, respectively. All the patients who had metastatic lesions, but showed lower than 4.5 ng/ml of ICTP, had a solitary lesion of bone metastasis. Although ICTP is not sensitive enough to detect an early stage of bone metastasis, it is a better biochemical marker than NTx for detecting bone metastasis from breast cancer.
- [Show abstract] [Hide abstract] ABSTRACT: Matrix metalloproteinases (MMP) are considered to play important roles in angiogenesis. In angiogenic processes, endothelial cells secrete MMP-2 or MMP-1 to dissolve the basement membrane or connective tissue around the vessels. MMP-7 (matrilysin) is secreted from the neovasculars induced by cancer and is a metastatic factor of colorectal cancer. The effect of matrilysin on angiogenesis is still unclear, however. We therefore examined the effect of MMP-7 on the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro. Our results showed that recombinant MMP-7 (rMMP-7) accelerated the proliferation of endothelial cells dose-dependently, and did so for endothelial cells cultured not only on type IV collagen, but also on type I collagen. MMP-7 also upregulated MMP-1, -2 secretion, but did not stimulate vascular endothelial growth factor (VEGF) secretion. From this study, we conclude that MMP-7 directly induces angiogenesis, and that therefore MMP-7 would be a good target of cancer therapy.
- [Show abstract] [Hide abstract] ABSTRACT: We report a 35-year-old woman with locally advanced mucinous carcinoma of the breast with sudden growth acceleration. A pea-sized mass developed into an ulcerated large tumor within 1 month. After the combination of chemotherapy, radiation and hyperthermia, a radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps. Histological examination revealed a pure mucinous carcinoma with axillary lymph node involvement. Estrogen and progesterone receptors were not detected in the tumor. Twenty-five months after treatment, there is no sign of recurrent disease. Pure mucinous carcinoma generally has a less aggressive growth pattern as defined by tumor size, adherence to the overlying skin/bottom fasciae, estrogen and progesterone receptor positive and primary lymph axillary lymph node metastases. This case showed completely opposite features to all of these typical biological features of pure mucinous carcinomas.
- [Show abstract] [Hide abstract] ABSTRACT: The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell-specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)-transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 microg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO-treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO-treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.
- [Show abstract] [Hide abstract] ABSTRACT: Brain metastases occur in 15% to 30% of breast cancer patients, usually as a late event. The patterns of metastases to different organs are determined by the tumor cell phenotype and interactions between the tumor cells and the organ environment. We investigated the gene expression profile occurring in brain metastases from a breast cancer cell line. We used cDNA microarrays to compare patterns of gene expression between the mouse breast cancer cell line Jyg MC (A) and a subline that often metastasis to brain, (B). By Microarray analysis about 350 of 21,000 genes were significantly up-regulated in Jyg MC (B). Many candidate genes that may be associated with the establishment of brain metastasis from breast cancer were included. Interestingly, we found that the expression of astrocyte derived cytokine receptors (IL-6 receptor, TGF-beta receptor and IGF receptor) were significantly increased in Jyg MC (B) cells. These results were confirmed by RT-PCR. These results suggest that cytokines produced by glial cells in vivo may contribute, in a paracrine manner, to the development of brain metastases from breast cancer cells.
- [Show abstract] [Hide abstract] ABSTRACT: We report a case of jejunal fistula due to late-appearing intraabdominal abscesses following ulcerative colitis (UC) surgery. A 52-year-old man who underwent total colectomy and ileal pouch anal canal anastomosis after perforation of the descending colon and panperitonitis during steroid treatment for ulcerative colitis. Histological examination of the resected specimen showed acute fulminating type of UC. He was admitted due to fever 6 months after surgery. Ultrasonography (US) and computed tomography (CT) showed an intraabdominal abscess in the upper left quadrant. X-ray examination with contrast medium showed an abscess cavity and 2 fistulas between the abscess cavity and jejnum, necessitating partial resection of the jejunam and drainage of the abscess cavity. Resected specimens did not show ulcerative colitis or Crohn's disease. After discharge, he was readmitted for fever and leukocytosis. X-ray examination with contrast medium showed the abscess cavity and an other fistula between the abscess cavity and jejnum. We conducted further partial resection of the jejunum and drainage after abscess curettage. The resected specimen did not show ulcerative colitis or Crohn's disease. The man has had no recurrence of symptoms or diagnostic imaging signs since discharge.
- [Show abstract] [Hide abstract] ABSTRACT: We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast-like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate-resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP-positive cells and the percentage of multinuclear cells. For the pit-forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone-resorbing activity of OCLs. CL treatment did not affect either the number of TRAP-positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer.
Hiratsuka Kyosai HospitalHiratuka, Kanagawa, Japan
Yokohama City University
Yokohama, Kanagawa, Japan
- Department of Medicine