Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Production of biological response modifiers through recombinant techniques has stimulated interest in immunotherapy of cancer. One of these, interleukin-2 (IL-2), will induce in vivo as well as in vitro proliferation of noncommitted T lymphocytes into lymphokine-activated killer (LAK) cells: cells cytolytic for a broad range of tumor cells. We have demonstrated earlier that immunotherapy with IL-2 and LAK cells will reduce tumor load and prolong survival in a significant way in an intraperitoneal (ip) tumor model as well as in other models. Nevertheless, mice die of one or two metastases escaping immunotherapy. Activation of the host immune system might boost endogenous IL-2 production. Activation might also enhance immunotherapy by increasing the necessary cofactors. Loco-regional allogeneic pretreatment ip 14 days prior to syngeneic tumor challenge did not enhance, but completely abrogated, ip IL-2 and LAK cell therapy (peritoneal cancer index, 0.6 +/- 0.3 vs 2.6 +/- 0.2, P2 = 0.003). Tumor bulk is not the reason for escape of immunotherapy either. One week after intracutaneous (ic) tumor inoculation a noncurative or sham tumor resection was performed, followed by IL-2 and LAK cell therapy either ip or in and around the tumor nodule. No significant difference in tumor diameter or survival of mice was seen. Allogenic tumor cells admixed with syngeneic tumor cells will induce an inflammatory reaction locally and regionally. This inflammatory reaction in the syngeneic host will enhance the treatment with IL-2. The allogeneic (P815) and syngeneic (MCA-105) tumor cell mixture was injected ic. Growth rate was retarded and survival prolonged in a significant way when the cell mixture was treated with ip IL-2 injections; no difference was seen when the admixture was not treated or the syngeneic ic tumor alone was treated with IL-2. We conclude that host immune status and recruitment of immunocompetent cells locally to the tumor site determine the outcome of immunotherapy with IL-2 and LAK cells.
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PMID:Local conditions in the host influence immunotherapy with interleukin-2 and LAK cells. 326 2

We investigated the correlation of intraoperative peritoneal lavage smear and gastric wall brushing smear cytology with macroscopic and histologic findings and prognosis, in 216 patients with gastric cancer. Some 196 of these patients underwent gastric resection and 20 did not. The incidence of positive cancer cells determined by these methods was significantly correlated with gastric resection, tumor invasion, and peritoneal dissemination. Among patients without macroscopic peritoneal dissemination, four were found to have positive peritoneal lavage smears or gastric wall brushing smears, respectively. The prognosis of these patients did not differ from that of patients with metastases to the adjacent peritoneum but not the distant peritoneum. These results suggest that peritoneal lavage smears and gastric wall brushing smears are useful for predicting the peritoneal cancer dissemination. Therefore we intend to target patients with no peritoneal metastases (Po) showing positive peritoneal cytology for intensive treatment.
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PMID:[Prognostic evaluation of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery]. 757 71

Laparoscopic surgery for malignant disease is highly controversial mainly due to the large number of abdominal wall metastases being reported. Previous experimental studies have particularly studied CO2 pneumoperitoneum and its effect on tumor development. The purpose of this study was to compare CO2- and air-induced pneumoperitoneum with regard to intraperitoneal tumor growth. Altogether 39 rats were injected intraperitoneally with 10(5) colonic tumor cells and randomly allocated into three groups: 13 rats had a pneumoperitoneum created with CO2, 13 with air, and 13 served as controls. Tumor development was determined semiquantitatively by a peritoneal cancer index scale after 12 days. CO2 and air pneumoperitoneum equally increased intraperitoneal tumor growth compared to controls. Pneumoperitoneum induced by CO2 and air seems to increase tumor load, but the mechanisms are not established. This finding supports the hypothesis that insufflation not only by causing tumor cell movements but in fact pneumoperitoneum per se and the used gas are involved in the development of abdominal wall metastases after laparoscopic surgery.
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PMID:Effective of pneumoperitoneum induced by carbon dioxide and air on tumor load in a rat model. 956 90

Our recent studies indicate that omental milky spots are frequently involved in the early stage of peritoneal cancer dissemination. We have used carcinoembryonic antigen (CEA)-specific RT-PCR for omental milky spots to predict peritoneal recurrence in gastric cancer patients. CEA mRNA was found to be positive in both 10 peritoneal washes and 16 greater omenta of 30 gastric cancer patients, including all 6 patients who showed positive results for both cytology and RT-PCR of peritoneal wash and omentum. Three of the 6 cases with positive RT-PCR in the greater omentum but not in the peritoneal wash showed recurrence of peritoneal carcinomatosa within 2 years after operation. Micrometastasis on omental milky spots was histologically confirmed in 6 of 30 gastric cancer cases. Non-specific band was detected only in the omentum of 1 case of 15 benign disease (7%), but not in peritoneal washes (0%), probably due to weak expression of CEA in mesothelial cells. Our results show that CEA-specific RT-PCR targeting micro-metastases on omental milky spots is more sensitive than targeting the peritoneal wash or conventional cytology, and suggest that this method is useful for the prediction of peritoneal recurrence in gastric cancer patients.
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PMID:Polymerase chain reaction for detection of carcinoembryonic antigen-expressing tumor cells on milky spots of the greater omentum in gastric cancer patients: a pilot study. 1149 26

Women from families with multiple cases of breast and ovarian cancer, specifically those who carry cancer-associated mutations of BRCA1 or BRCA2 are at increased life-time risk for peritoneal carcinoma, even after previous surgery to remove the ovaries, fallopian tubes and uterus. Hereditary breast-ovarian cancer (HBOC) syndrome and the associated BRCA1 and BRCA2 mutations are particularly prevalent in women of Jewish lineage, and specific BRCA1 and BRCA2 germline mutations have been linked with peritoneal carcinoma and HBOC syndrome in Jewish populations, especially those of Ashkenazi descent. This review presents the currently available data and looks forward toward further and better understanding of peritoneal carcinoma in women with inherited susceptibility. Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and associated with BRCA1 and BRCA2 mutations are serous carcinomas, which is equivalent with the proportion of ovarian cancers that are serous carcinomas in similar patients. The best indications are that while many peritoneal carcinomas in genetically susceptible women may arise directly from malignant transformation of the peritoneum, others might represent metastases from primary ovarian or fallopian tube carcinomas. Although the incidence of borderline ovarian tumors may not be increased in HBOC syndrome kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, these individuals could be susceptible to malignant transformation of borderline lesions of the ovaries and peritoneum. Moreover, recent reports raise the question of possibly increased risk in Jewish carriers of germline BRCA1 mutations for uterine papillary serous carcinoma, which could be the source of metastasis to the peritoneum in some cases. The penetrance of cancer-associated BRCA1 mutations for ovarian cancer is estimated to be 11%-54%, and for BRCA2 mutations the penetrance for ovarian cancer is 11%-23%. So far, available screening methods appear to be insufficient for early detection of many ovarian cancers. Prophylactic oophorectomy has been found to reduce the risk for ovarian cancer in women from HBOC kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, leaving a residual risk for peritoneal carcinomatosis of well less than 5%. Therefore, surgical removal of the ovaries, fallopian tubes and uterus, after child-bearing has been completed and by early in the fifth decade of life, are appropriate prophylactic procedures in women whose genetic susceptibility puts them at increased risk for cancers of mullerian tract origin, including ovarian and fallopian tube carcinomas and possibly serous carcinoma of the uterus. Hysterectomy, as well as salpingo-oophorectomy, removes the gynecologic organs targeted for malignant transformation in genetically susceptible women and simplifies decisions regarding hormone replacement therapy and chemical prophylaxis and treatment of breast cancer. Unless a transabdominal operative approach is otherwise indicated, laparoscopic-assisted transvaginal techniques are well suited for intra-abdominal exploration, cytology, biopsies and prophylactic salpingo-oophorectomy and hysterectomy in women with hereditary susceptibility to gynecologic cancer.
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PMID:Peritoneal carcinoma in women with genetic susceptibility: implications for Jewish populations. 1551 51

The aim of this prospective study was to determine the clinical benefits of introducing peroperative frozen section analysis into the surgical management policy of women referred with an adnexal mass suspicious of ovarian cancer. All women surgically managed at the Northern Gynaecological Oncology Centre, Gateshead, UK, between July 1, 2002, and June 30, 2003, where frozen section analysis had been utilized were included for analysis. Correlation was determined between cases surgically staged following the frozen section result and the clinical need for staging based on the pathologic diagnosis from the paraffin section. During the 12-month period, 130 women underwent frozen section analysis. Paraffin section diagnoses included 74 benign tumors, 11 borderline tumors, 34 primary epithelial cancers, 5 nonepithelial cancers, and 6 metastatic tumors. All primary epithelial ovarian cancers were correctly identified as requiring a staging procedure based on the frozen section result. Four of seventy-four cases reported as benign on frozen section analysis were underdiagnosed; two were later diagnosed on paraffin section as borderline tumors and a further two as malignant (one low-grade adenosarcoma and one primary peritoneal cancer). Of the 130 cases, 55 (42.3%) underwent a staging procedure based on the frozen section result. The value of frozen section analysis in determining the need for the performance of a staging procedure had the following statistical test results: sensitivity = 92%, specificity = 88%, positive predictive value = 82%, and negative predictive value = 95%. Excluding the borderline tumors, metastatic tumors, and primary peritoneal tumor where staging did not impact subsequent clinical management, the statistical test results for frozen section analysis in determining the need for a staging procedure were sensitivity = 97%, specificity = 95%, positive predictive value = 90%, and negative predictive value = 99%. The clinical benefits of introducing frozen section analysis in the surgical staging policy of women with an adnexal mass suspicious of ovarian malignancy included avoidance of a surgical staging procedure in 95% of cases identified on paraffin section analysis to be benign. This benefit was without compromising the avoidance of chemotherapy in true stage I epithelial ovarian cancer cases. Additional benefits included the confirmation of malignancy where extraovarian lesions were suggestive but not indicative of malignant disease, and the intraoperative identification of metastatic disease of nonovarian origin.
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PMID:"True" versus "apparent" stage I epithelial ovarian cancer: value of frozen section analysis. 1651 66

Lectins (asialo-receptor family) are expressed on a number of tumors that develop peritoneal metastases. To demonstrate that fluorescence imaging based on lectin binding is applicable for a variety of tumors, we conjugated BODIPY to avidin (avidin-BODIPY), and studied the efficacy of tumor targeting in 9 cancer cell lines in vitro and an ovarian cancer cell line in vivo using a murine peritoneal cancer model. All 9 cell lines showed specific intracellular accumulation with avidin-BODIPY on fluorescence microscopy and flow cytometry. In vivo spectral molecular imaging clearly visualized the peritoneal tumor foci with avidin-BODIPY, whereas, deglycosylated avidin-BODIPY (neutravidin-BODIPY) showed only minimal fluorescence from the tumor foci and was accompanied by higher background signals. These results suggest the lectin-targeted molecular imaging technique using a targeted green fluorescence probe is potentially useful in a wide variety of cancers with a proclivity for dissemination in the peritoneal space.
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PMID:Targeted optical imaging of cancer cells using lectin-binding BODIPY conjugated avidin. 1690 40

When used in the context of multidisciplinary team discussion, image guided biopsy using ultrasound (US) or computed tomography (CT) guidance is of value in planning management of women with suspected ovarian cancer and peritoneal carcinomatosis (PC) of uncertain aetiology. It is essential in women believed to have ovarian cancer but with poor performance status or with advanced disease believed beyond the scope of primary cytoreductive surgery for whom staging surgical pathology will not be obtained. It provides a site-specific primary tumour diagnosis in 93% of cases and it should replace diagnostic laparoscopy or laparotomy for this purpose. It allows provision of primary (neoadjuvant) chemotherapy based on a firm histological diagnosis. It is mandatory in women with a history of cancer whose metastases may mimic ovarian cancer (e.g. breast, GI tract, melanoma). More women with prior breast cancer who re-present with peritoneal cancer will have a new gynaecological primary than recurrence of their original primary tumour; the two options require radically different therapies. Finally it is a valuable problem solving tool in situations of diagnostic uncertainty, e.g. unusual imaging patterns of disease such as PC with bilateral solid ovarian masses or non-enlarged ovaries and with an unusual tumour marker profiles suggesting primary tumours outwith the ovary. The technique is simple, safe and effective and can be combined with palliative drainage of ascites at the same procedure.
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PMID:Image guided biopsy in the management of cancer of the ovary. 1696 69

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.
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PMID:120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study. 1720 60

Surgical therapy of peritoneal surface malignancy from colorectal origin in combination with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) has now become an established treatment approach in very few specialised centres. A peritonectomy procedure is possible to perform with additional HIPEC in patients. An experimental model to simulate peritonectomy procedure and HIPEC does not exist so far in rats. Nevertheless, animal models seem to be very important for evaluation of new therapeutic opportunities and toxicity of different multimodal therapies. In a first step we analysed the surgical tumour debulking of peritoneal surface malignancy in rats. A peritoneal surface malignancy from colonic origin was induced in 75 male BD IX rats. Twenty one days after induction of peritoneal surface malignancy rats were randomised and animals intend to create an operation with surgical tumour debulking. There was no tumour growth in two animals. The aim of the peritonectomy procedure was the complete tumour reduction. In this study the results of the surgical approach will be described. A complete tumour reduction (R0) was achieved in 34 animals. In 39 rats a macroscopic tumour deposit was left behind (R2). The intraoperative experimental Peritoneal Cancer Index (ePCI) was used to describe tumour weight and number of tumour inoculations. Both parameters were found to be dependent factors of complete tumour reduction. Six animals died due to therapeutical interventions. Surgical tumour debulking in rats with peritoneal surface malignancy is possible with high reliability and a low mortality rate. This animal model could be an important step for investigation of multimodal treatment options and toxicity in treatment regimens of peritoneal surface malignancy.
Clin Exp Metastasis 2008
PMID:First surgical tumour reduction of peritoneal surface malignancy in a rat's model. 1830 91


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