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)

A group of 100 human liver samples obtained from three different network sources was divided into groups of normal, cirrhotic, metastatic cancer and other disease groups. These samples were analyzed for amounts of cytochrome P-450 IA2, IIC, IIE1 and IIIA and epoxide hydrolase per unit of microsomal protein using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical staining. For each enzyme the amount of protein detected varied by two orders of magnitude, even within the set of normal liver samples. With respect to the liver samples judged to be normal, the cirrhotic samples showed decreased levels of P-450 IA2 and IIE1 and epoxide hydrolase (P less than .05). The level of P-450 IIIA proteins also appeared lower but the high variance did not allow such a statistically valid conclusion. The liver samples obtained from metastatic cancer patients did not show decreased levels of any of the proteins examined, and levels of P-450 IIC proteins were enhanced in this group compared to the controls. In the samples obtained from patients with other liver diseases, the only major change was a decrease in the level of P-450 IA2. These findings are of use in explaining some of the known effects of hepatic disease on the in vitro and in vivo metabolism of certain drugs.
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PMID:Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemical analysis of surgical liver samples. 200 81

In summary, neither radiation nor surgery is clearly superior. The benefits of surgery include: 1) emotional satisfaction that the tumor has been removed, 2) accuracy of surgical staging, 3) preservation of the ovaries, 4) no secondary uterine cancer (a very uncommon problem), and 5) complications that are more readily correctable. Radiation offers the major advantages of being useful in most patients regardless of age or medical condition and is the choice for large cancers. Because stage IB cervical cancer is a very diverse pathological entity with a number of potential prognostic factors (including cell type, depth of invasion, tumor volume, lymphatic space involvement, and occult lymph node metastases), and because patients present with a number of other conditions (including excess weight, advanced age, prior pelvic surgery or infection, and severe medical illness), we are fortunate to have two good methods for treating cervical cancer. Prospective randomized studies will be necessary in the future to better define specific advantages in the various clinical settings. But, in general, the following have proven most expedient: 1) class I hysterectomy, for microinvasive cancer of 3 mm invasion or less without lymphatic space involvement, 2) modified, extended hysterectomy (class II) and pelvic lymphadenectomy for lesions of 3 mm and lymph vascular space involvement or when the lesion seems to just exceed 3 mm and for very early adenocarcinoma, 3) an extended hysterectomy (class III) and pelvic lymphadenectomy for larger IA2, IB, and IIA lesions that are less than 4 cm, particularly for the pregnant or younger patient, and when ovarian conservation is desired, 4) radiation therapy is used for lesions over 4 cm and for women with severe medical illness making extended hysterectomy too hazardous, 5) combination therapy and chemotherapy are now reserved for study in poor prognosis patients with very large lesions (greater than 6 cm), occult metastases, and unfavorable histologic criteria (Table 2).
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PMID:Surgery or radiation for early cervical cancer. 228 54

The International Federation of Gynecology and Obstetrics instituted a change in the classification for carcinoma of the cervix with a new substage IA2. The criteria for this substage exceed the generally accepted criteria for microinvasion. Fifty patients with early invasive squamous cell carcinoma of the cervix were treated from 1976 through 1983 with a cone biopsy followed by a radical hysterectomy and pelvic lymph node dissection. These patients were reviewed to evaluate the ability to make the histologic diagnosis and to examine the natural history of the disease with maximal treatment. Histologically positive margins were found at the time of cone biopsy in 66% (33/50) of the patients. Negative margins at the time of cone biopsy were identified in 34% (17/50) of the patients. Residual invasive disease at the time of radical hysterectomy was found in 24% (4/17) of the patients with negative margins. Two of the 50 patients had positive lymph nodes. Three patients had recurrent metastatic disease. This study demonstrates that a preoperative diagnosis of stage IA2 invasive squamous cell carcinoma of the cervix is a difficult diagnosis to establish and creates a therapeutic dilemma regarding treatment.
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PMID:Stage IA2 squamous carcinoma of the cervix: difficult diagnosis and therapeutic dilemma. 236 May 73

Retrievable pathological specimens and clinical data on 70 patients with microinvasive carcinoma diagnosed on surgical specimens from cone biopsy or hysterectomy (Stage IA) were reviewed and compared to pertinent findings in the literature with the intent of evaluating diagnostic criteria and defining pathological features that may influence the outcome by therapy. Emphasis was given to the preoperative assessment emphasizing that both an accurate colposcopic evaluation and a detailed pathological analysis may reliably point to a conservative therapeutic approach. Increasing depth of stromal invasion was associated with lesion width as well as with endocervical extension, as measured on colposcopy, microcolpohisteroscopy, and histology. Lymph-vascular space involvement was significantly related to depth of invasion. Two patients of 28 with dissected nodes had node metastases as well as lymph-vascular space involvement. Both developed a pelvic recurrence. One had a > 1- to < or = 3-mm invasion depth, the other a > 3- to < or = 5-mm lesion invasion. While advocating a conservative procedure for Stage IA1, we suggest discrimination with regard to Stage IA2 because we believe that lymph-vascular involvement should be meticulously evaluated. In fact, > 1- to < or = 3-mm lesions without lymph-vascular space involvement can be conservatively treated, while for any other lesion falling within the Stage IA2 category a modified radical histerectomy plus pelvic lymphadenectomy should be recommended.
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PMID:Presurgical assessment and therapy of microinvasive carcinoma of the cervix. 759 Apr 83

Ninety-four patients with squamous cell carcinoma invading the cervical stroma to a depth of >3.0-5.0 mm with 7 mm or less in horizontal spread (FIGO Stage IA2) were evaluated. Depth and lateral extent of stromal invasion were verified using an ocular micrometer. Cell type and lymph vascular space invasion (LVSI) were recorded in each case. Patients were treated primarily by radical hysterectomy with pelvic lymphadenectomy, and those with lymph node metastases were offered postoperative radiation. Following treatment, patients were seen at 3-month intervals for 2 years, and every 6 months thereafter. The mean duration of follow-up was 6.9 years (range 0.4-23.5 years). Seven of 94 patients (7.4%) had lymph node metastases. Five patients had 1 positive node, 1 patient had 2 positive nodes, and 1 patient had 3 positive nodes. Five patients developed recurrent cancer and 4 died of disease. LVSI was present in 31 cases (33%). Tumor recurrence was significantly increased in patients with positive LVSI (9.7% vs 3.2%). The 5-year survival rate of patients with LVSI was 89% vs 98% in patients without this finding (P = 0.058). The 5-year survival rate of all Stage IA2 cervical cancer patients was 95%. Patients with Stage IA2 cervical cancer have a significant risk of lymph node metastases and should be treated by radical hysterectomy with pelvic lymphadenectomy. LVSI is an important prognostic variable in these patients and should be recorded in all cases.
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PMID:Lymph node metastases and prognosis in patients with stage IA2 cervical cancer. 889 59

Eleven patients with stage IA2-IIA carcinoma of the cervix have been treated by combined laparoscopic-vaginal radical hysterectomy and bilateral pelvic lymphadenectomy (3-Stage IA2, 5-stage IB, 3-Stage IIA). The patients were unselected. Three patients had bulky (&gte; 5 cms) tumors, one of whom weighed 239 lbs; one had prior anterior-posterior repair, was apareunic and had significant vaginal narrowing; two patients had extensive pelvic adhesions, one of whom also had a 480 gram uterus. Pelvic lymph node metastases were present in one patient and paracervical lymph node metastases in one. The technique used has undergone significant modification. The laparoscopic phase of the procedure contributes much more to the operation than the lymphadenectomy for it allows a symbiotic partitioning of the operation into the laparoscopic and vaginal components. Only those steps of the operation are carried out vaginally that are easier to perform from below (division of the uterosacral and cardinal ligaments, unroofing of the ureter), and they are made much easier by the preceding laparoscopic phase of the operation. Laparoscopic development of the para-vesical and para-rectal spaces makes vaginal entry into these spaces very straightforward, and laparoscopic division of the uterine artery facilitates vaginal unroofing of the ureter. By allowing the proximal ureter to be freed from the medial leaf of the broad ligament, and the proximal attachments and blood supply of the uterus to be divided, the laparoscopic phase of the operation also permits the cervical ligaments to be divided before the ureters are freed from the vesico-cervical ligament, which helps to avoid a Schuchardt incision in most patients.
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PMID:Laparoscopic-Vaginal Radical Hysterectomy 907 93

We assessed the feasibility of sentinel lymph node detection using technicium-99 radiocolloid lymphatic mapping for predicting lymph node metastases in early invasive cervical cancer. Thirty patients with cervical cancer (stages IA2-IIA) underwent preoperative lymphoscintigraphy using technicium-99 intracervical injection and intraoperative lymphatic mapping with a handheld gamma probe. After dissection of the sentinel nodes, the standard procedure of pelvic lymph node dissection and radical hysterectomy was performed as usual. The sentinel node detection rate was 100% (30/30). There were seven (23.3%) cases of microscopic lymph node metastases on pathologic analysis. All of them had sentinel node involvement. Therefore, the sensitivity of sentinel node identification for prediction of lymph node metastases was 100%, and no false negative was found. Preoperative lymphoscintigraphy, coupled with intraoperative lymphatic mapping, located the sentinel nodes accurately in our study patients. This sentinel node detection method appears to be feasible for predicting lymph node metastases.
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PMID:Sentinel node detection with radiocolloid lymphatic mapping in early invasive cervical cancer. 1582 11

Classical midgut carcinoids are serotonin-secreting tumors derived from enterochromaffin cells in the gut. Metastatic disease represents a therapeutic challenge and immunotherapy implies a novel approach for treatment. In order to define antigens suitable for T-cell therapy with a preferential expression in midgut carcinoid tissue a broad screening of genes with preferential neuroendocrine restriction, genes described as over-expressed in various malignancies, and genes encoding cancer-testis associated antigens was performed. The expression of 32 genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in normal tissues. Immunohistochemistry (IHC) was used to evaluate protein expression. Expression is shown of genes that have previously not been observed in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is confirmed of genes that encode pivotal proteins in enterochromaffin cells, such as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin should be further investigated as potential target antigens for T cell-mediated immunotherapy of midgut carcinoids.
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PMID:Gene expression in midgut carcinoid tumors: potential targets for immunotherapy. 1584 4

This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (</=45 vs >45 years: P = 0.0079), FIGO stage (IB1-IIA </=4 cm vs IB2-IIA >4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.
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PMID:Ovarian metastases in early-stage cervical cancer (IA2-IIA): a multicenter retrospective study of 1965 patients (a Cooperative Task Force study). 1730 69

Recurrence of early-stage cervical cancer after primary surgery represents a considerable clinical problem, and, so far, few reliable markers for prediction of recurrence exist. Thus, the prognostic value of the malignancy grading score (MGS) classification system was evaluated in 82 patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stages IA2, IB, and IIA) and long-time follow-up (5-16 years). Recurrence or not, the likelihood of lymph node metastases and reproducibility of the MGS semiquantitative system were tested. The prognostic power of the MGS to identify high-risk cases prone to recurrence in patients lacking lymph node metastases at primary surgery was a main purpose of the present study. The semiquantitative MGS classification system was performed independently by 2 pathologists unaware of prognosis and clinical data using light microscopy. Routine hematoxylin and eosin sections from surgical specimens were used, and investigation area was defined in the deep part of the tumor. Data-based image analysis was also used to investigate if objective morphometric parameters could add any prognostic power to MGS. The 5-year survival for the whole patient group was 92%. Malignancy grading score of greater than 17 risk points was statistically highly significant in predicting relapse and lymph node metastases (n = 82). High-risk cases lacking lymph node metastases (n = 70) were also statistically associated with high MGS. Depth of invasion and vascular invasion were statistically related to recurrence. Objective image analysis of nuclear parameters was of no additional statistical value for the prediction of outcome. The MGS classification system proved to be a useful tool in predicting recurrence and lymph node metastases and, most importantly, was a predictor of high-risk patients without metastases at primary surgery.
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PMID:Prognosis of early cervical cancer (FIGO Stages IA2, IB, and IIA) in northern Norway predicted by malignancy grading score and objective morphometric image analysis. 1875 56


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