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Liver Metastasis (liver + metastasis)
Selected AbstractsWhole genome analysis for liver metastasis gene signatures in colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Dong Hyuk Ki Abstract Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. © 2007 Wiley-Liss, Inc. [source] Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colonPATHOLOGY INTERNATIONAL, Issue 8 2005Tomoya Kato Herein is presented a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron-dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors' knowledge, the present case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma. [source] Cytology of pancreatic acinar cell carcinomaDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2006Edward B. Stelow M.D. Abstract Acinar cell carcinoma (ACC) of the pancreas is extremely uncommon and its cytologic features have rarely been described. We describe the cytologic features of cases we have seen, review the literature regarding its cytologic features and discuss the pitfalls that may be encountered and the use of immunohistochemistry for its diagnosis. We searched our databases for all cases of histologically confirmed pancreatic ACC which had undergone prior fine needle aspiration (FNA) of the primary pancreatic lesion. The clinical histories, radiographic and sonographic findings, cytologic features, original cytologic diagnoses, and final histologic diagnoses were reviewed. Four cases of pancreatic ACC were found that had undergone FNA prior to histologic confirmation of the diagnoses. They were from 2 men and 2 women aged 50,75 yr. All masses were in the head of the pancreas, 2 had apparent peri-pancreatic adenopathy and 1 had an apparent liver metastasis. On review, all 4 had had diagnostic material on cytology samples. Original cytologic diagnoses included "acinar cell carcinoma," "pancreatic endocrine tumor," "favor neuroendocrine tumor, low-grade" and "non-diagnostic specimen." The cytologic features included small to moderate-sized loose groups with numerous single cells, prominent acinar formation, little anisonucleosis and prominent nucleoli. The cytologic features showed significant overlap with those of pancreatic endocrine tumors. Diagn. Cytopathol. 2006; 34:367,372. © 2006 Wiley-Liss, Inc. [source] Human T-lymphotropic virus type-1 related adult T-cell leukemia/lymphoma presenting as a parotid mass diagnosed by fine-needle aspiration biopsyDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2004Guo-Xia Tong M.D., Ph.D. Abstract A 48-yr-old black woman with a history of blood transfusions for menorrhagia secondary to uterine fibroids but no known Caribbean association presented with a 6-wk history of a rapidly enlarging right parotid mass. At the time of presentation, she could not close her right eye. An aspiration biopsy showed small, medium, and large lymphoma cells with angulated nuclei, red macronucleoli, and basophilic cytoplasm with fine vacuoles. Flow cytometry indicated a (CD25+/CD7,) T-cell lineage, suggesting an human T-lymphotropic virus (HTLV) 1-related T-cell leukemia/lymphoma, which was confirmed by polymerase chain reaction (PCR)-based amplification on DNA extracted from fresh tissue with specific oligonucleotide primers for HTLV-1 DNA sequence. Histology showed interstitial infiltration and destruction of the parotid parenchyma by lymphoma cells without involvement of adjacent lymph nodes. Total body CT scan and magnetic resonance imaging (MRI) studies were negative for lymphadenopathy but showed liver metastasis. To our knowledge, this is the first reported case of HTLV-1-related primary parotid lymphoma as the initial presentation of adult T-cell leukemia/lymphoma. Diagn. Cytopathol. 2004;31:333,337. © 2004 Wiley-Liss, Inc. [source] Analysis of clinical outcomes and prognostic factors of neoadjuvant chemoradiotherapy combined with surgery: intraperitoneal versus extraperitoneal rectal cancerEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2006E. BENZONI md Neoadjuvant chemoradiotherapy (CRT) is a widely purposed and performed treatment for rectal cancer. Downstaging effects possibly enhance the rate of curative surgery and may enable sphincter preservation in low-lying tumours. The current study examines the clinical outcomes in patients enrolled in a neoadjuvant CRT-surgery protocol for rectal cancer, distinguishing between intraperitoneal and extraperitoneal cancer. From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were enrolled in a single-centre, not randomized study based on 5-week sessions of radiotherapy associated with a 30-day protracted venous 5-FU infusion followed by surgical resection. The study population was divided into two groups according to the localization of the tumour: 18 intraperitoneal and 40 extraperitoneal (EPt). Fifty-eight patients were treated with neoadjuvant CRT and surgery. Overall mortality rate was 25.9%, no deaths were recorded during hospitalization; 10 patients (all EPt) died because of recurrence. Significant differences in disease-free survival and overall survival rates were found between intraperitoneal vs. extraperitoneal tumours (P = 0.006), both intraperitoneal vs. extraperitoneal tumours N0 (P = 0.04 and P < 0.05) and intraperitoneal vs. extraperitoneal tumours N+ (P < 0.05). We diagnosed all local recurrence and liver metastasis in extraperitoneal tumours (t = 0.02 and t = 0.04), and only one case of lung metastasis arose from intraperitoneal cancer. Extraperitoneal tumours could be more aggressive than intraperitoneal ones, spreading more precociously, and/or less responsive to the neoadjuvant CRT because of their localization rather than biological differences. Aside from lymph node status, the location of the tumour with respect to the peritoneum border, is also a prognostic factor of survival in rectal cancer treated by neoadjuvant CRT and surgery. [source] Stage-specific alterations of the genome, transcriptome, and proteome during colorectal carcinogenesis,GENES, CHROMOSOMES AND CANCER, Issue 1 2007Jens K. Habermann To identify sequential alterations of the genome, transcriptome, and proteome during colorectal cancer progression, we have analyzed tissue samples from 36 patients, including the complete mucosa-adenoma-carcinoma sequence from 8 patients. Comparative genomic hybridization (CGH) revealed patterns of stage specific, recurrent genomic imbalances. Gene expression analysis on 9K cDNA arrays identified 58 genes differentially expressed between normal mucosa and adenoma, 116 genes between adenoma and carcinoma, and 158 genes between primary carcinoma and liver metastasis (P < 0.001). Parallel analysis of our samples by CGH and expression profiling revealed a direct correlation of chromosomal copy number changes with chromosome-specific average gene expression levels. Protein expression was analyzed by two-dimensional gel electrophoresis and subsequent mass spectrometry. Although there was no direct match of differentially expressed proteins and genes, the majority of them belonged to identical pathways or networks. In conclusion, increasing genomic instability and a recurrent pattern of chromosomal imbalances as well as specific gene and protein expression changes correlate with distinct stages of colorectal cancer progression. Chromosomal aneuploidies directly affect average resident gene expression levels, thereby contributing to a massive deregulation of the cellular transcriptome. The identification of novel genes and proteins might deliver molecular targets for diagnostic and therapeutic interventions. © Wiley-Liss, Inc. [source] Interaction of tumour biology and tumour burden in determining outcome after hepatic resection for colorectal metastasesHPB, Issue 2 2010Dhanny Gomez Abstract Aims:, To determine the outcome of colorectal liver metastasis (CRLM) patients based on tumour burden, represented by tumour number and size, and tumour biology as assessed by an inflammatory response to tumour (IRT) and margin positivity. Methods:, Data were collated from CRLM patients undergoing resection from January 1993 to March 2007. Patients were divided into: low (,3 metastases and/or ,3 cm); moderate (4,7 metastases and/or >3,,5 cm); and high (,8 metastases and/or >5 cm) tumour burden. Results:, Seven hundred and five patients underwent resection, of which 154 (21.8%), 262 (37.2%) and 289 (41.0%) patients were in the low, moderate and high tumour burden groups, respectively. The 5-year disease-free (P < 0.001) and overall (P < 0.001) survival were significantly different between the groups. IRT (P < 0.001), extent of resection (P < 0.001) and margin (P < 0.001) also differed between the groups. Sub-group analysis revealed that IRT was the only adverse predictor for disease-free and overall survival in the low group. In the moderate group, IRT predicted poorer disease-free survival on multi-variate analysis. In the high group, R1 resection and transfusion were predictors of poorer disease-free survival and age ,65 years, R1 resection and IRT were adverse predictors of overall survival. Conclusion:, Resection margin influenced the outcome of patients with high tumour burden, hence the importance of achieving clear margins. IRT influenced the outcome of patients with less aggressive disease. [source] Usefulness of follow-up after pancreatoduodenectomy for carcinoma of the ampulla of VaterHPB, Issue 2 2007LAURENCE CHICHE Abstract Background: The prognosis for carcinoma of the ampulla of Vater (CAV) is better than for pancreatic cancer. The 5-year survival median rate after resection of CAV is 45%, but late recurrences remain possible. Several survival factors have been identified (lymph nodes, perineural invasion), but few data are available on the type of recurrences, their impact and their management. Patients and methods: A total of 41 patients treated by pancreatoduodenectomy (PD) for CAV from 1980 to 2003 were studied retrospectively. Patient selection, long-term survival recurrence rate and recurrence treatment were reviewed. Univariate and multivariate proportional hazards analysis were conducted on this series. Results: The mean follow-up was 48 months. Five-year survival was 62.8%. Eleven patients had recurrences (6,67 months). Recurrence was associated with time to all-causes death (hazard ratio [HR] 4.3, p=0.003). Factors predictive of recurrence were perineural invasion (HR 5.3, p=0.02), lymph node invasion (HR 5.3, p=0.02) and differentiation (HR 0.2, p=0.05). Three patients underwent surgical R0 treatment of their recurrences. Two who presented with solitary liver metastasis are alive and disease-free. Conclusions: Recurrence represents a serious threat in the prognosis of CAV after surgery. Some of these recurrences, in particular liver metastases, are accessible for a curative treatment. This finding supports the usefulness of a close and long-term follow-up after surgery to improve survival of patients with CAV, especially in the group of patients with a good prognosis. [source] Lung metastases after liver resection or cryotherapy for hepatic metastasis from colorectal cancer,there is a difference!HPB, Issue 2 2006T. D. Yan Background. The most common site of colorectal extra-abdominal metastases is the lung. The relative risk of lung metastases after resection and cryotherapy has not previously been compared. Methods. All patients underwent an extensive preoperative staging including clinical examination, abdominal computed tomography (CT) and abdominal angio-CT to assess their hepatic disease. Two groups of patients were compared in this study (hepatic resection alone and hepatic cryotherapy with or without resection). A retrospective analysis of prospectively collected data was performed to assess the incidence and disease-free interval of pulmonary metastasis after surgical treatment of colorectal liver metastasis. Results. This paper clearly shows two differences regarding pulmonary metastases between patients treated with resection only and cryotherapy with or without resection. Among the 10 clinical variables, cryotherapy had the greatest correlation with pulmonary metastases (p=0.004). A patient who undergoes hepatic resection only has a probability of 35% for developing pulmonary recurrence, compared with 51% following cryotherapy. Cryotherapy was also independently associated with shorter pulmonary disease-free interval (p=0.036). Conclusion. There clearly is a higher risk of pulmonary metastasis after cryotherapy than after resection, whether this is related to selection of patients or a direct deleterious procedural effect requires more study. [source] A salvage treatment for solid liver metastasis after radical resection of Klatskin tumourHPB, Issue 4 2003Yuji Nakagawa Background Long-term survival has not been described following surgical resection for liver metastasis after radical resection of an advanced hilar bile duct carcinoma (Klatskin tumour). One such patient who developed liver metastasis after radical treatment for stage IVA (pTNM) hilar cholangiocarcinoma has survived 5.5 years after resection of the liver metastasis followed by chemotherapy. Case report A 50-year-old man developed a solid liver metastasis in segment VIII 17 months after radical resection of a stage IVA (pT3 pN1 M0) Klatskin tumour followed by postoperative radiotherapy (54 Gy) and systemic chemotherapy (oral UFT 450 mg/day plus intravenous cisplatin 20 mg on 5 consecutive days each month). The patient is alive at 7 years after the primary resection followed by resection of the liver metastasis plus further systemic chemotherapy comprising oral UFT combined with intravenous adriamycin (ADM) and mitomycin C (MMC). Conclusion Aggressive salvage resection surgery can be an effective component of a multidisciplinary treatment regimen, even for a postoperative liver metastasis that developed after radical resection of an advanced Klatskin tumour, provided that the metastasis is solid and has not failed local-regional control. [source] Mesenchymal stem cells enhance growth and metastasis of colon cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2010Kei Shinagawa Abstract Recently, mesenchymal stem cells (MSCs) were reported to migrate to tumor stroma as well as injured tissue. We examined the role of human MSCs in tumor stroma using an orthotopic nude mice model of KM12SM colon cancer. In in vivo experiments, systemically injected MSCs migrated to the stroma of orthotopic colon tumors and metastatic liver tumors. Orthotopic transplantation of KM12SM cells mixed with MSCs resulted in greater tumor weight than did transplantation of KM12SM cells alone. The survival rate was significantly lower in the mixed-cell group, and liver metastasis was seen only in this group. Moreover, tumors resulting from transplantation of mixed cells had a significantly higher proliferating cell nuclear antigen labeling index, significantly greater microvessel area and significantly lower apoptotic index. Splenic injection of KM12SM cells mixed with MSCs, in comparison to splenic injection of KM12SM cells alone, resulted in a significantly greater number of liver metastases. MSCs incorporated into the stroma of primary and metastatic tumors expressed ,-smooth muscle actin and platelet-derived growth factor receptor-, as carcinoma-associated fibroblast (CAF) markers. In in vitro experiments, KM12SM cells recruited MSCs, and MSCs stimulated migration and invasion of tumor cells through the release of soluble factors. Collectively, MSCs migrate and differentiate into CAFs in tumor stroma, and they promote growth and metastasis of colon cancer by enhancing angiogenesis, migration and invasion and by inhibiting apoptosis of tumor cells. [source] Whole genome analysis for liver metastasis gene signatures in colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Dong Hyuk Ki Abstract Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. © 2007 Wiley-Liss, Inc. [source] Metastatic cutaneous leiomyosarcoma from primary neoplasm of the mesenteryINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2001Kyoung Jin Kim MD A 31-year-old South Korean woman was referred to the dermatology department from the oncology department for the evaluation of a subcutaneous nodular lesion on the back. Three years before, she noted a palpable, fingertip-sized, nontender mass on her right lower abdomen. The mass had increased in size slowly. One year ago, she visited a local clinic and physical examination revealed a 7 × 8 × 7 cm, slightly tender, deep-seated mass on the right lower quadrant of the abdomen. The mass on the ilial mesentery was resected by surgical exploration and tissue examination revealed leiomyosarcoma. She refused adjuvant chemotherapy. Approximately 3 months later, she re-visited the clinic with a tender, subcutaneous nodule on the back. Cutaneous examination revealed a solitary, 2 × 2 cm, well-defined, hard, movable, subcutaneous nodule on the upper back without skin color change (Fig. 1). She complained of tenderness on touching the lesion. Histologic examination of a biopsy specimen showed irregularly arranged spindle cells scattered throughout the dermis. They were arranged in haphazardly oriented or interweaving fascicles. Most of the spindle cells possessed elongated nuclei with blunt ends and some cells had a polygonal outline with irregularly shaped nuclei (Fig. 2). There were many mitoses: 3,4 per high-power (× 400) field. Immunohistochemically, smooth muscle actin and desmin were positive in most of the tumor cells (Fig. 3). S-100 reactivity was not observed. A diagnosis of metastatic leiomyosarcoma was made. About 1 month later, computed tomography showed two, ill-defined, heterogeneous, low attenuation masses in the right lobe of the liver, suggesting liver metastasis. The patient was treated with chemotherapy for 2 months and remains in good condition. Figure 1. 2 × 2 cm, solitary, well-defined, hard, movable, subcutaneous nodule without any overlying skin change Figure 2. (a) Characteristic findings of cutaneous leiomyosarcoma with markedly high cellularity and densely packed transverse and longitudinal fascicles of cells (hematoxylin and eosin, × 40). (b) High magnification of the neoplasm revealing spindle cells with blunt-ended nuclei, pleomorphism, and mitotic figures (hematoxylin and eosin, × 200) Figure 3. Dense cytoplasmic reactivity for smooth muscle actin is apparent (smooth muscle actin, × 200) [source] Outcome of self-expandable metallic stents in low-grade versus advanced hilar obstructionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2008Rungsun Rerknimitr Abstract Background:, Self-expandable metallic stents (SEMS) are known to provide a longer patency time than plastic stents for malignant biliary obstructions including hilar obstruction. However, studies that focus on the efficacy of SEMS in low-grade and advanced hilar obstructions are still scanty. Methods:, Ninety four patients with malignant hilar obstructions were enrolled (six were later excluded). Patients were divided into two groups according to their Bismuth levels. Group A were patients with Bismuth I (n = 53). Group B were patients with Bismuth II, III and IV (n = 35). Technical success, complications, jaundice resolution, stent patency time, and patients' survival were analyzed. Results:, Our intention-to-treat analysis showed that group A had a significant lower rate of post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis than group B; 16.1% versus 44.7%, (P < 0.01). Four patients from group B still had persistent jaundice. Our per protocol analysis demonstrated that median stent patency time in groups A and B were not statistically different (74 vs 60 days). Median survival time in groups A and B were also not statistically different (90 vs 75 days). In both groups, those without liver metastasis had significantly better patency and survival time than those with liver metastasis (P = 0.010 and 0.027, respectively). Conclusions:, In patients with hilar obstruction, liver metastasis is one of the main factors that determine survival of the patient. Patency times of SEMS in both low-grade and advanced obstructions are comparable. However, in the advanced group, there is a significant risk of post-ERCP cholangitis. [source] Enucleation of an advanced esophageal gastrointestinal stromal tumor with liver metastasisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2006Chien-Sheng Huang [source] Safety and efficacy of curative intent surgery for peri-ampullary liver metastasisJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Mechteld C. de Jong MD Abstract Introduction The management of patients with peri-ampullary liver metastasis remains controversial. We sought to assess the safety and efficacy of curative intent surgery for peri-ampullary liver metastasis. Methods Between 1993 and 2009, 40 patients underwent curative intent surgery (resection and/or radiofrequency ablation (RFA)) for peri-ampullary liver metastasis. Clinicopathologic and outcome data were collected and analyzed. Results Location of the primary tumor was pancreas head (n,=,20), ampulla of Vater (n,=,10), distal bile duct (n,=,5), or duodenum (n,=,5). Most patients (n,=,27) presented with synchronous disease, while 13 patients presented with metachronous disease following a median disease-free interval of 22 months. Most patients (n,=,25) presented with hepatic metastasis from pancreaticobiliary origin (pancreatic or distal common bile duct) compared with 15 patients who had metastasis from an intestinal-type primary (ampullary or duodenal). There were no differences in metastatic tumor number or size between these groups (P,>,0.05). Post-operative morbidity and mortality was 30% and 5% respectively. Overall 1- and 3-year survival was 55% and 18%. Patients who underwent resection of liver metastasis from intestinal-type tumors experienced a longer survival compared with patients who had pancreaticobiliary lesions (median: 13 months vs. 23 months; P,=,0.05). Conclusion Curative intent surgery for peri-ampullary liver metastasis was associated with post-operative morbidity and a 5% mortality rate. Although the overall survival benefit was modest, patients with liver metastasis from intestinal-type tumors experienced improved survival following resection of liver metastasis compared with pancreaticobiliary lesions. J. Surg. Oncol. 2010;102:256,263. © 2010 Wiley-Liss, Inc. [source] CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL-mediated pathwayLIVER INTERNATIONAL, Issue 4 2003Katrien Vekemans Abstract The mechanisms involved in colorectal carcinoma with liver metastasis are not well known. Metastasizing colon carcinoma cells express more FasL than primary colon carcinoma cells and cancer cells induce apoptosis in hepatocytes by the Fas/FasL pathway. Therefore, this study focused on Fas/FasL expression and functionality in rat liver sinusoidal endothelial cells (LSECs) and CC531s colon carcinoma cells in vitro and in vivo. RT-PCR and immunochemistry revealed Fas and FasL in LSECs and CC531s, respectively. Functionality of Fas was assessed in vitro by incubation with human recombinant FasL (1,100 ng/ml) with or without enhancer. At concentrations of 10 and 100 ng/ml with enhancer, respectively 21% and 44% of endothelial cells showed signs of apoptosis using Hoechst 33342/propidium iodide staining and electron microscopy. In co-cultures, apoptosis could be detected in endothelial cells neighboring the CC531s and could be inhibited by an antagonistic FasL antibody. Moreover, 18 h after mesenteric injection of CC531s, the sinusoidal endothelium revealed disruption. In conclusion, (i) CC531s cells induce apoptosis in LSECs in vitro by using Fas/FasL; (ii) CC531s cells damage the sinusoidal endothelial lining in vivo; and (iii) this might provide FasL-positive tumor cells a gateway towards the hepatocytes. [source] Prognosis and surgical treatment of gastric cancer invading adjacent organsANZ JOURNAL OF SURGERY, Issue 7-8 2010Ming Zhang Abstract Background:, The prognostic factors and surgical management of gastric cancer invading adjacent organs remains controversial. The aim was to provide valuable prognostic and surgical information on patients with gastric cancer invading adjacent organs. Methods:, The retrospectively study included 367 patients who underwent gastric resection for gastric cancer invading adjacent organs. Clinicopathologic variables were evaluated as predictors of long-term survival by univariate and multivariate analyses. Multivariate analysis was performed using Cox's proportional hazards model. Results:, The five-year survival rate was 10.1%, and median survival period was 14 months. The five-year survival rate was influenced by histologic type, lymph node metastasis, liver metastasis, peritoneal dissemination, extent of lymph node dissection and curability of operation. Of these, independent prognostic factors were lymph node metastasis (N2, N3 versus N0, N1, relative risk 2.028, P < 0.001), liver metastasis (present versus absent, relative risk 1.582, P= 0.023) and curative resection (no versus yes, relative risk 1.719, P < 0.001). A significant survival benefit for curative resection was observed with a five-year survival rate of 21.5% compared with non-curatively resected cases (5.1%). Conclusions:, In patients with gastric cancer invading adjacent organs, three independent prognostic factors were lymph node metastasis, liver metastasis, and curative resection. For patients with gastric cancer invading adjacent organs, we recommend performing combined organ resection in patients with locally advanced gastric carcinoma regardless of curability. [source] Xanthogranulomatous cholecystitis masquerading as malignancy with liver metastasisANZ JOURNAL OF SURGERY, Issue 12 2009Deborshi Sharma MS, FMAS, MRCSEd No abstract is available for this article. [source] Decrease in intrahepatic CD56+ lymphocytes in gastric and colorectal cancer patients with liver metastasesAPMIS, Issue 12 2009MAYA GULUBOVA The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3+ lymphocytes, natural killer (NK)-like T lymphocytes (NKT) expressing the CD3+ CD56+ phenotype, CD56+ NK cells, CD4+, and CD8+ T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two-color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3+ CD56+ cells in metastatic livers, but not in nonmetastatic livers (11.9 ± 10.3 vs 24.2 ± 13.6%, p = 0.02). The percentage of intrahepatic CD3,CD56+ cells was also decreased in patients with metastases compared to those without (10.1 ± 11.6 vs 16.6 ± 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4+, CD8+, and CD56+) were present in the metastatic tissue, although the number of CD56+ cells was almost twice lower. We found a low prevalence of tumor-infiltrating CD4+, CD8+, and CD56+ cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3,CD56+ and CD3+ CD56+ cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor-infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control. [source] Long-term results of gastrectomy for ,-fetoprotein-producing gastric cancer,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2010M. Inoue Background: ,-Fetoprotein (AFP)-producing gastric cancer is a rare tumour. It is said to have a high incidence of liver metastasis and poor prognosis. This study sought to evaluate long-term outcomes in such patients. Methods: Records of consecutive patients with gastric carcinoma who underwent preoperative measurement of serum AFP levels and gastrectomy were reviewed to identify those who satisfied the following criteria: preoperative AFP level exceeding 40 ng/ml with a decrease after gastrectomy, or raised preoperative AFP level (10,39 ng/ml) and resected tumour showing histologically characteristic features or immunohistochemically positive AFP production. Results: Of 3374 patients with gastric cancer, 53 (1·6 per cent) met the selection criteria. Tumours were characterized by a high incidence of nodal (79 per cent) or liver (53 per cent) metastasis. Preoperative serum AFP levels showed no correlation with tumour size, depth of invasion, disease stage or survival. The 5-year survival rate was 34 per cent. Five patients survived after recurrence following multimodal treatment. A rising AFP level during follow-up always led to tumour recurrence, but the level remained normal in 11 of 31 patients with recurrence. Conclusion: AFP-producing tumours represent a small subgroup of gastric cancer with high metastatic potential. Postoperative serum AFP level can help predict recurrence but a normal level does not mean absence of recurrence. Prognosis is not as poor as previously thought, and multimodal treatment may be worthwhile even in patients with recurrent tumour. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2000Dr M. Kobari Background: The prognosis of patients with resected pancreatic cancer remains poor. This study evaluated the effect of adoptive immunotherapy (AIT) using intraportal infusion of lymphokine-activated killer (LAK) cells after curative resection and intraoperative radiation therapy (IORT) on advanced pancreatic cancer. Methods: Twenty-nine consecutive patients with advanced pancreatic cancer (Japan Pancreas Society stage III or IV) were divided into two groups. The control group (n = 17) underwent tumour resection and IORT. The treatment group (n = 12) underwent resection, IORT and intraportal infusion of LAK cells combined with recombinant interleukin 2 (rIL-2). The incidence of liver metastasis and the survival rate of these two groups were compared. Results: Although the overall survival between groups was not statistically different (P = 0·082), there were more patients (four) alive 3 years after operation in the test group (36 per cent versus zero), and the incidence of liver metastases in the treatment group was significantly lower (three of 12 versus ten of 15; P < 0·05). LAK therapy influenced survival positively in multivariate analysis. Conclusion: These preliminary observations suggest that AIT warrants further study as a possible adjuvant for patients undergoing curative resection and IORT for pancreatic cancer. © 2000 British Journal of Surgery Society Ltd [source] Rate of bilirubin regression after stenting in malignant biliary obstruction for the initiation of chemotherapyCANCER, Issue 11 2008How soon should we repeat endoscopic retrograde cholangiopancreatography? Abstract BACKGROUND. This study was conducted to evaluate the rate of regression of bilirubin after stent placement for malignant biliary obstruction. METHODS. Records were reviewed from October 2002 to September 2005 for patients who underwent endoscopic retrograde cholangiopancreatography with stent placement. The time to achieve a bilirubin level ,2 mg/dL was the primary endpoint because this is the level required by most chemotherapy protocols. Patient variables included type of cancer, liver metastasis, recent chemotherapy, baseline creatinine, and international normalized ratio (INR). Stent variables included type, dimension, stricture location, and sphincterotomy. RESULTS. In total, 156 patients were included in the analysis: Ninety-three patients achieved a poststent bilirubin level ,2 mg/dL, 29 patients failed because of stent failure, and 34 patients failed because of inadequate follow-up. The time required for 80% of patients to achieve normalization was more than doubled in those who had prestent bilirubin levels ,10 mg/dL (6 weeks) compared with those who had prestent bilirubin levels <10 mg/dL (3 weeks). The following variables were identified as statistically significant: prestent bilirubin level, stricture location, liver metastasis, and INR. The cancer type, recent chemotherapy, stent type and diameter, and sphincterotomy were not statistically significant variables. CONCLUSIONS. The rate of bilirubin normalization after biliary stenting was highly dependent on the prestent bilirubin level. Endoscopic intervention should be considered in patients who fail to achieve adequate normalization of serum bilirubin in 6 weeks if prestent bilirubin level was ,10 mg/dL and in 3 weeks if their prestent bilirubin level was <10 mg/dL. Independent variables, such as diffuse liver metastases, stricture outside the common bile duct, and elevated INR had predictive value for bilirubin normalization. Cancer 2008. © 2008 American Cancer Society. [source] Pattern of carcinoembryonic antigen drop after laparoscopic radiofrequency ablation of liver metastasis from colorectal carcinomaCANCER, Issue 1 2006Mohammed Ghanamah M.D. Abstract BACKGROUND Laparoscopic radiofrequency ablation (RFA) is being increasingly used for local control of hepatic metastasis from colorectal carcinoma (CRC). After surgical resection of colorectal liver metastasis, carcinoembryonic antigen (CEA) values fall within 2 weeks, making this a useful parameter to follow shortly after surgery. Little is known, however, about the expected pattern of the CEA drop after RFA. METHODS From September 1998 to October 2002, RFA to CRC liver metastasis was performed on 144 patients. A subset of 17 patients were studied who had no evidence of extrahepatic disease preoperatively, had all detectable tumor ablated intraoperatively, and who on long-term follow-up (up to 15 months) had no evidence of recurrent disease. Serum CEA was determined preoperatively, on the first postoperative day, at 1 week, and every 3 months afterwards. A computed tomography (CT) scan of the abdomen and pelvis was obtained every 3 months postoperatively. RESULTS Ten (58.8%) patients showed an increase in CEA on postoperative Day 1, averaging 38.3% compared with the preoperative value. CEA then fell to 50% of the preoperative value, on average, on Day 7 postoperatively and only reached its nadir at 3 months. CONCLUSIONS Unlike resection patients, those undergoing ablation show an initial rise in CEA, probably due to release from the ablated tissue. Although heating of RFA would be expected to destroy CEA, the initial rise and slow drop postoperatively argue for a release of immunoreactive CEA from the ablated zone. This slow decline in CEA indicates that several months should pass before assessing the extent of potential residual disease. Cancer 2006. © 2006 American Cancer Society. [source] High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancerCANCER SCIENCE, Issue 3 2010Koji Ando (Cancer Sci 2010; 101: 639,645) Gastric cancers show high frequency of DNA aneuploidy, a phenotype of chromosomal instability. It is suggested that the abnormal spindle assembly checkpoint is involved in DNA aneuploidy, but the underlying mechanism is still unclear. We studied the mechanism by assessing the expression of BUBR1 in gastric cancer. The DNA ploidy patterns of 116 gastric cancer samples obtained from the Department of Surgery and Science at Kyushu University Hospital were analyzed. Of those, DNA aneuploidy was seen in 70 (60.3%) cases of gastric cancer. The expression of BUBR1 was studied by immunohistochemistry in 181 gastric cancer samples and by real-time RT-PCR in several gastric cancer cell lines. Ninety-one (50.3%) cases had high expression of BUBR1 and those cases correlated significantly with DNA aneuploidy (P < 0.05). Also high expression of BUBR1 cases had significant correlation with deep invasion, lymph node metastasis, liver metastasis, and poor prognosis. In gastric cancer cell lines, high expression of BUBR1 had a significant relationship with DNA aneuploidy (P < 0.05). Then, gastric cancer cell lines MKN-28 and SNU-1 were transfected with full-length BUBR1 to observe the significance of the change in BUBR1 expression. Enforced expression of BUBR1 resulted in changes to the ploidy pattern and high Ki-67 expression. Collectively, our clinical and in vitro data indicate that high expression of BUBR1 may be one of causative factors for the induction of DNA aneuploidy and progression of gastric cancer. [source] Glypican 3-expressing gastric carcinoma: Distinct subgroup unifying hepatoid, clear-cell, and ,-fetoprotein-producing gastric carcinomasCANCER SCIENCE, Issue 4 2009Tetsuo Ushiku Gypican-3 (GPC3) has been recognized as an oncofetal protein in hepatic neoplasms and yolk sac tumors. To characterize a distinct subgroup of gastric carcinoma (GC) expressing GPC3 (GPC3-GC), primary and metastatic GC tissues were evaluated by immunohistochemistry with special focus on their related entities: hepatoid, clear-cell, and ,-fetoprotein-producing GC. GPC3-GC was defined as focal GPC3-GC when 10,49% of neoplastic cells were positive, and as diffuse GPC3-GC when more than 50% of cells were positive. Among 926 GC cases, 101 (11%) were GPC3-GC, of which 45 were diffuse and 56 were focal GPC3-GC. Specific histological patterns, such as the hepatoid and clear-cell patterns, were frequently observed in diffuse GPC3-GC (38 and 49%, respectively) and in focal GPC3-GC (4 and 25%, respectively), whereas these patterns were extremely rare in GPC3-negative GC. Immunoreactive ,-fetoprotein was only identified in GPC3-GC (38% of diffuse and 14% of focal GPC3-GC). Both diffuse and focal GPC3-GC showed nodal metastasis more frequently (67 and 55%, respectively) than GPC3-negative GC (34%), and the diffuse GPC3-GC had significantly more T2,4 and M1 stage cases. GPC3 immunostaining was present in 57 out of 61 nodal metastases (93%) and in all four liver metastases examined. Importantly, diffuse GPC3 expression was observed in the liver metastasis, even if the primary tumor was focal GPC3-GC. GPC3-GC is a distinctive group of GC, which unifies hepatoid, clear-cell, and ,-fetoprotein-producing GC. GPC3 is expected to be a target of forthcoming immunotherapy for a patient bearing this specific type of GC. (Cancer Sci 2009; 100: 626,632) [source] Methionine-enkephalin secreted by human colorectal cancer cells suppresses T lymphocytesCANCER SCIENCE, Issue 3 2009Hitoshi Ohmori The role of methionine-enkephalin (MENK) as an immunomodulator in colorectal carcinomas (CRC) was examined. MENK was produced in CT26, IEC6A, Colo320, and HT29 CRC cell lines but not in IEC6 intestinal cells. MENK secretion was associated with tumorigenicity and metastasis of CRC cells in syngeneic rodent models. The MENK concentration in subcutaneous tumors of CT26 and IEC6A CRC cells exhibited an inverse correlation with the number of tumor-infiltrating T lymphocytes. MENK inhibited the growth of MOLT-4 T-lymphoblastic cells in a dose-dependent manner. Furthermore, it increased the phosphorylation level of c-Jun N-terminal kinase and induced apoptosis in MOLT-4 cells. MENK-induced apoptosis was abrogated by a c-Jun N-terminal kinase inhibitor. Immunohistochemical analysis revealed moderate to strong expression of MENK in 33 (54%) of 61 CRC. MENK expression was associated with Dukes' staging, nodal metastasis, and liver metastasis. The MENK concentration in tumor tissues was higher in Dukes' C cases than in Dukes' B cases. MENK expression was associated with tumor-infiltrating T lymphocytes, especially those belonging to the CD4+ subset. These findings suggest that MENK secreted by CRC cells caused escape of the host from the effects of immunity. (Cancer Sci 2009; 100: 497,502) [source] Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinomaCANCER SCIENCE, Issue 7 2007Keiichi Iwaya Directed movement of normal cells occurs when actin-related protein 2 and 3 complex (Arp2/3 complex) triggers the actin polymerization that forms lamellipodia immediately after binding to WAVE2. In order to determine whether the same mechanism correlates with liver metastasis from colorectal cancer, paired mirror sections of 154 cancer specimens (29 cases with liver metastasis and 125 cases without liver metastasis in which T factor, gender, primary tumor site, and age at operation were matched) were examined immunohistochemically for the localization of Arp2 and WAVE2. Expression of both Arp2 and WAVE2 was detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not detected in the normal colonic epithelial cells. Univariate analysis showed that the colocalization was significantly predictive of liver metastasis (risk ratio [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95), and tumor budding (RR 4.00) were significant predictors. Among these, colocalization and lymphatic invasion were shown to be independent risk factors by multivariate analysis. Another 59 colorectal specimens were examined for mRNA expression of Arp2 by real time polymerase chain reaction. High mRNA levels of Arp2, that in situ hybridization revealed to be expressed by the cancer cells, were significantly associated with liver metastasis. However, its effect was absorbed by the influence of risk of the colocalization that is closely related to high expression of Arp2. These results indicate that the colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma. (Cancer Sci 2007; 98: 992,999) [source] Ras Farnesylation Inhibitor FTI-277 Restores the E-Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer MetastasisCANCER SCIENCE, Issue 9 2002Jeong-Seok Nam The E-cadherin/catenin cell adhesion system is often down-regulated in epithelial tumors. This is thought to play an important role in cancer invasion and metastasis, and restoration of this system may suppress metastatic spread of cancer. In this study, the effects of a Ras farnesylation inhibitor (FTI-277) on E-cadherin-mediated cell-cell adhesion and metastatic potential were examined. In cell aggregation assays, FTI-277 stimulated aggregation of colon, liver and breast cancer cells. In vitro cultures of cancer cells showed that FIT-277 induced strong cell-cell contact. Immunoblotting analysis showed that FTI-277 increased E-cadherin/catenin (,, , and ,) expression and strongly stabilized E-cadherin/catenin with the actin cytoskeleton. Northern blotting studies indicated that the observed increase in the E-cadherin/catenin protein content was due to increased expression of their genes. After inoculation of the spleens of mice with severe combined immunodeficiency (SCID) with cancer cells, FTI-277 treatment for 3 weeks markedly reduced splenic primary tumor growth and the rate of liver metastasis compared with control counterparts. Our data demonstrate that FTI-277 can activate functioning of the E-cadherin-mediated cell adhesion system, which is associated with suppression of cancer cell metastasis. Therefore, selective inhibition of Ras activation may be useful for preventing cancer metastasis. [source] Long-term outcome of transpupillary thermotherapy as primary treatment of selected choroidal melanomaACTA OPHTHALMOLOGICA, Issue 7 2009Raffaele Parrozzani Abstract. Purpose:, To evaluate prospectively, on a long-term range, the clinical outcomes of transpupillary thermotherapy (TTT) as primary treatment of selected choroidal melanoma. Methods:, Seventy-seven eyes of 77 patients affected by small posterior choroidal melanoma were treated with TTT as a sole treatment, using an infrared diode laser at 810 nm according to a standard procedure. Follow-up was longer than 36 months. Results:, Seventeen tumours (22%) were parapapillary (PP) and 60 tumours (78%) were non-parapapillary (NPP) in location. Mean follow-up was 55.2 ± 17.9 months in PP tumours and 44.3 ± 23.7 months in NPP tumours. Thirteen (76%) PP tumours and 55 (92%) NPP tumours regressed (P > 0.05). Nine tumours recurred: seven were retreated using Iodine-125 brachytherapy and two were enucleated (both parapapillary). Four patients (5%) developed liver metastasis and died during follow-up. Tumour thickness was found to be predictive of recurrence (odds ratio: 4.3). Complications were found in 20 eyes (26%): macular pucker in 11 (14%), macular oedema in three (4%), retinal vein occlusion in six (8%), vitreous and subretinal haemorrhage in two (3%) and neovascular glaucoma in three (4%). PP tumours had more local complications (but this was not statistically significant; P > 0.05). Complications appeared more frequently in tumours treated with more than one TTT session (P = 0.01), and time-risk to develop intraocular complications seems longer in the PP group, without reaching statistical significance (P = 0.07). Conclusion:, TTT may be a clinically effective method for conservative treatment of selected, non-parapapillary, small posterior choroidal melanoma. [source] | ||||||||||||||||||||||||||||