Transvaginal ultrasound for preoperative assessment of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of deep myometrial infiltration in patients with endometrial cancer, comparing subjective and objective methods. METHODS: An extensive search was performed in MEDLINE (PubMed) and EMBASE for studies published between January 1989 and December 2014. The eligibility criterion was use of TVS for preoperative assessment of myometrial infiltration by subjective evaluation and/or objective measurements. Objective measurements included, specifically, the approaches of Gordon (ratio of the distance between endometrium-myometrium interface and maximum tumor depth to the total myometrial thickness) and Karlsson (endometrial tumor thickness/anteroposterior uterine diameter ratio), in women with endometrial cancer, using the surgical pathological data as a reference standard. Study quality was assessed using the QUADAS-2 tool. RESULTS: Our extended search identified a total of 184 citations, among which we examined the full text of 24 articles. Overall pooled sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of TVS for detecting deep myometrial infiltration were 82% (95% CI, 76-87%), 81% (95% CI, 76-85%), 4.3 (95% CI, 3.6-5.3) and 0.22 (95% CI, 0.16-0.30), respectively. We did not observe differences among the three methods in terms of diagnostic performance. Significant heterogeneity was found for sensitivity and specificity of all three methods (I(2) range, 60.6-95.0). The main limitation was that very few studies compared different approaches in the same set of patients. CONCLUSION: Diagnostic performance of TVS for detecting deep myometrial infiltration in women with endometrial cancer is moderate.

Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b).

The cell cycle inhibitor p15(INK4b) is frequently inactivated by homozygous deletion together with p16(INK4a) and p19(ARF) in some types of tumors. Although the tumor suppressor capability of p15(INK4b) is still questioned, it has been found to be specifically inactivated by hypermethylation in hematopoietic malignancies in the absence of p16(INK4a) alterations. Here we show that, in vitro, p15(INK4b) is a strong inhibitor of cellular transformation by Ras. Surprisingly, p15(INK4b) is induced in cultured cells by oncogenic Ras to an extent similar to that of p16(INK4a), and their expression is associated with premature G(1) arrest and senescence. Ras-dependent induction of these two INK4 genes is mediated mainly by the Raf-Mek-Erk pathway. Studies with activated and dominant negative forms of Ras effectors indicate that the Raf-Mek-Erk pathway is essential for induction of both the p15(INK4b) and p16(INK4a) promoters, although other Ras effector pathways can collaborate, giving rise to a stronger response. Our results indicate that p15(INK4b), by itself, is able to stop cell transformation by Ras and other oncogenes such as Rgr (a new oncogene member of the Ral-GDS family, whose action is mediated through Ras). In fact, embryonic fibroblasts isolated from p15(INK4b) knockout mice are susceptible to transformation by the Ras or Rgr oncogene whereas wild-type embryonic fibroblasts are not. Similarly, p15(INK4b)-deficient mouse embryo fibroblasts are more sensitive than wild-type cells to transformation by a combination of the Rgr and E1A oncogenes. The cell cycle inhibitor p15(INK4b) is therefore involved, at least in some cell types, in the tumor suppressor activity triggered after inappropriate oncogenic Ras activation in the cell.

Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice.

We tested the antineoplastic effect of the farnesyltransferase inhibitor L-744,832 in mammary and lymphoid tumors overexpressing the N-ras proto-oncogene in transgenic mice. Mice bearing mammary tumors were randomly assigned to receive daily 40 mg/kg s.c. injections of this compound (experimental group, n = 6) or vehicle (control group, n = 6) per day for 5.5 weeks. Treatment with the compound significantly reduced the mammary tumor mean growth rate in the experimental group (-0.7 mm3/day), as compared with the control group (+28.2 mm3/day; P < 0.001). There was a significant difference in lymphoma incidence at the end of the treatment between the experimental (0 of 6) and the control (3 of 6) groups (P < 0.05). Therefore, this compound is effective in treating in vivo mammary carcinomas and lymphomas in which an activated N-Ras pathway drives tumorigenesis. The number of apoptotic figures in mammary tumors was significantly higher (P = 0.04) in the experimental (14.7 +/- 8.1) than it was in the control (5.7 +/- 3.5) group, indicating that apoptotic induction could contribute to the mechanism of antitumor activity of this compound. We analyzed the level of processing of N-Ras and H-Ras after immunoprecipitation and Western blotting of protein extracts obtained from mammary tumors treated with L-744,832 or vehicle, either in vivo or in vitro (after primary culture of the same tumors), and from several in vitro treated control cell lines. In all compound-treated mammary tumors and cell lines, H-Ras was mostly unprocessed (more so after in vitro than after in vivo treatment), whereas N-Ras remained mostly processed. Both H-Ras and N-Ras remained fully processed in all vehicle-treated samples. These findings are consistent with a less intense antineoplastic effect of the treatment with the compound in our N-ras model than the effect previously reported for the same compound in H-ras transgenics. In addition, the finding that, in compound-treated mammary tumors, the N-Ras protein remains mainly processed suggests that, in our model, other proteins in addition to Ras may be a target for the compound. Our results and the previous findings of frequent N-ras activation in human hematopoietic malignancies support a role for L-744,832 in the treatment of lymphomas and of mammary carcinomas with an activated N-Ras pathway, as well as the testing of a farnesyl protein transferase inhibitor in humans to establish its clinical relevance.

NF1 inactivation cooperates with N-ras in in vivo lymphogenesis activating Erk by a mechanism independent of its Ras-GTPase accelerating activity.

We crossed transgenic mice overexpressing the N-ras proto-oncogene (RasTg) with mice carrying one inactivated copy of the NF1 tumor suppressor gene (NF1+/-) to assess their possible cooperation in tumorigenesis. We have found a significant increase in the incidence of lymphomas in animals with both lesions (RasTg NF1+/-), as compared with animals with single lesions. The mechanism of this cooperation appears to be independent of the NF1 GTPase activating activity since the level of Ras-GTP in primary cultures of tumor tissue do not differ among animals with double and with single lesions. Nevertheless, the finding of significantly higher levels of Erk-1 and Erk-2 activation in lymphomas in the RasTg NF1+/- than in the RasTg group suggests that this cooperative effect may be in part explained by increased signaling through the Erk pathways. Consistent with a role for Erk activation in transformation is the additional observation that Erk-1 and Erk-2 activation is significantly increased in lymphomas as compared with normal spleen. This activation is likely to occur by phosphorylation of previously synthesized and inactive Erk proteins since, despite differences in activation, Erk-1 and Erk-2 expression is similar in normal and lymphoid tissue in all groups. The observed cooperation in in vivo lymphomagenesis between N-ras overexpression and NF1 inactivation emphasizes the importance of searching for additional functions for the NF1 protein and of intensifying the screening for NF1 mutations in human lymphomas.

[Hemangiomatous lesions with lymphangiectasias in the large intestine]. / Lesiones hemangiomatosas con linfangiectasias en intestino grueso.

We present the case of a 16 year-old male who presented intestinal hemorrhages since childhood; he was operated in emergency for microhemangiomas located in sigmoid colon and rectum. This lesion can be considered as a complex vascular hamartoma. We review the literature and discuss the differences between this lesion and angiodysplasia.

[Cervical lymphangioma in adults. Description of 2 cases]. / Lymphangiomes cervicaux chez l'adulte. Description de deux cas.

Cervical lymphangioma is an uncommon entity, usually reported in children, rarely in adults. We report two cases in adults and present a review of the literature. Cervical lymphangioma involves congenital and cystic abnormalities derived from lymphatic vessels with a progressive and unpainful growth. Diagnosis can be suggested by clinical features and CT or MRI findings. Final diagnosis is based on postoperative histology. Surgery is indicated. Complete removal is more easily achieved in adults than in children. Recurrences are thus more frequent in adults.

[Osteochondroplastic tracheobronchopathy, osteochondromas and recurrent sinusitis. Apropos a case]. / Traqueobroncopatía osteocondroplástica, osteocondromas y sinusitis de repetición. A propósito de un caso.

We describe the case of a patient with pneumonia presenting an atelectatic component at the front segment of the left upper Lobe (LUL) due to osteochondroplastic tracheobronchopathy (OT). The patient had been operated of an osteochondroma in the left perque and presented a proliferative bone lesion in the right femur suggesting the sam problem at this level. We discuss if that could be a casual association. We also analyze the potential relationship of OT and recurrent sinusitis, which was also present in this patient.

[Diagnostic and therapeutic management in malignant neck tumors of unknown origin. Our experience in the last 5 years]. / Manejo diagnóstico y terapéutico en tumores malignos cervicales de origen desconocido. Nuestra experiencia en los últimos cinco años.

The AA. analyzed 37 cases of metastatic neck cancer from unknown primary sites treated at the Oncologic Unit from 1986 to October 1991. This group account for 7 percent of total cervicofacial tumors seen. Factors that affected survival include the symptoms of consult, the control of cervical disease after treatment and surgery. The survival was 50 percent at two years and the rate of neck disease control amounted to 57.7 percent.

[Morphometric and stereologic nuclear values obtained from the study of a population suffering from nasopharyngeal carcinoma]. / Valores morfométricos y estereológicos nucleares obtenidos en el estudio de una población con carcinoma de nasofaringe.

Computer nuclear morphometry and stereology are attractive methods because its objectivity and cheapness allowing histologic diagnosis when identifying minimal variations respectively the normality and also detect negligible disparities between anormal cells which could escape to the assessment of the pathologist. We present the data gained from several morphogenic and stereologic parameters resulting of measurements of tumoral cells procured from 40 patients with nasopharyngeal carcinomata. Middle values have been: nuclear area 27.70 microns 2; nuclear perimeter 20.80 microns; nuclear factor of form 0.81 microns; nuclear outline index 4.01; nuclear orientation angle 87.29 degrees; nuclear ellipsiticity 704.14; nuclear regularity 61.83; middle lineal length 4.30, middle linear distance 107.94; and nuclear volume 118.80 microns 3. Our series is the largest studied till now of all found in the literature. Comparison our data with those of previous publications.

[Solitary extramedullary plasmocytoma of oropharynx]. / Plasmocitoma solitario extramedular orofaríngeo.

Report on a solitary extramedullary plasmacytoma case, an entity rarely diagnosed in daily practice, because of its low incidence. When the process occurs is seen fundamentally located at upper aero-digestive tract. Our patient was a 34-year-old man, who was diagnosed as oropharyngeal plasmacytoma with the peculiarity that the lesion feigned a benign one wether for the clinical features or the macroscopical aspect. The patient underwent surgery and postoperative rontgentherapy, after discarding a systemic disease. Till now the evolution proved good.

[Changes in the nuclear morphometry in oropharyngeal epidermoid carcinoma after induction chemotherapy]. / Cambios en la morfometría nuclear del carcinoma epidermoide de orofaringe tras quimioterapia de inducción.

A cytomorphic, stereological study was made by computerized image analysis of six nuclear morphometric variables and one stereological nuclear variable. Variables were measured on 150 randomly selected tumor cells in oropharyngeal biopsies from 44 patients with oropharyngeal cancer who had not responded completely to induction chemotherapy. The nuclei of tumoral cells were larger (mean nuclear area, perimeter, and volume), more rounded, and had a less irregular nuclear contour index.

[Nasal leiomyosarcoma]. / Leiomiosarcoma nasal.

Leiomyosarcoma is an infrequent soft-tissue tumor that generally occurs in the myometrium and gastrointestinal tract. Primary tumors of the veins are unusual and generally occur in the inferior vena cava and only exceptionally in peripheral veins, such as the jugular or its branches. We report a case of leiomyosarcoma located in the left inferior turbinate. The 87 year-old male patient presented nasal obstruction and recurrent nosebleed. He had pulmonary and mediastinal metastases at the time of diagnosis.

[Cervicothoracic angiomyolipoma: an unusual tumor located at a site difficult to reach for surgery]. / Angiomiolipoma cervicotorácico: una tumoración inusual en una localización de difícil abordaje quirúrgico.

Angiomyolipoma is an uncommon hamartomatous renal tumor very prone to spontaneous bleeding. However it is possible to find it in extrarenal sites, being the liver the most frequent one. The rest of sites recorded in literature are exceptional. In fact, to our knowledge, this is the first case reported of cervicothoracic settlement of an angiomyolipoma. This rare location, together with its marked tendency to bleed bleeding determinate a complicated diagnoses a difficult surgical approach.

[Prognostic value of morphometry and nuclear stereology in laryngeal epidermoid carcinoma]. / Valor pronóstico de la morfometría y estereología nuclear en el carcinoma epidermoide laríngeo.

BACKGROUND AND METHODS: A series of 70 consecutive patients with laryngeal carcinoma treated by induction chemotherapy is reported. The prediction of the response to induction chemotherapy was evaluated by nuclear morphometric and stereological analysis of the tumor cells. RESULTS: Statistically significant differences were found in the nuclear form factor (FF, p < 0.021) and nuclear contour index (NCI, p < 0.017) between the groups of patients with a complete response (CR), partial response (PR) or no response (NR) to induction chemotherapy. Comparison of the groups of patients with partial response or complete response to IC with the group with no response yielded statistically significant differences in the nuclear form factor (FF, p < 0.002), nuclear contour index (NCI, p < 0.0032) and nuclear orientation angle (NOA, p < 0.036). CONCLUSION: Nuclear morphometric analysis of the tumor cells was a useful tool for predicting response to induction chemotherapy in a significant number of the patients with laryngeal tumors in our series.

Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth advantage for astrocytes.

Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an increased frequency. To gain insight into the function of the Nf1 gene product as a growth regulator for astrocytes, we examined mice heterozygous for a targeted Nf1 mutation. In our previous studies, we demonstrated increased numbers of proliferating astrocytes in Nf1 heterozygote (Nf1+/-) mice in vivo. We now show that cultured Nf1+/- astrocytes exhibit a cell-autonomous growth advantage in vitro associated with increased p21-ras pathway activation. Furthermore, we demonstrate that Nf1+/-;wild-type N-ras mice have a similar astrocyte growth advantage in vitro and in vivo as either oncogenic N-ras or Nf1+/-; oncogenic N-ras mice. Lastly, mice heterozygous for targeted defects in both Nf1 and p53 as well as Nf1 and Rb exhibit 3- and 2.5-fold increases in astrocyte proliferation in vivo, respectively, suggesting that abnormalities in Nf1- and p53/Rb-regulated pathways cooperate in the heterozygous state to confer a growth advantage for brain astrocytes. Collectively, these results provide evidence for a cell-autonomous growth advantage in Nf1+/- astrocytes and suggest that some of the brain pathology in individuals with NF1 might result from reduced, but not absent, NF1 gene function.

[Plasmacytoma of the testis: report of a case]. / Plasmocitoma de testículo: presentación de un caso.

We report on a case of testicular plasmacytoma in a patient with multiple myeloma (MM), who is currently in a state of remission following chemotherapy and radiotherapy. The literature is reviewed, and testicular involvement in plasma cell neoplasms is discussed.

Detection of single and associated lesions of the Bcl-1, Bcl-2, Bcl-6, c-myc, p53 and p16 genes in B-cell non-Hodgkin's lymphomas: value of molecular analysis for a better assignment of the histologic subtype.

BACKGROUND AND OBJECTIVE: Molecular genetic abnormalities have been frequently described in non-Hodgkin's lymphomas (NHL). These lesions have been associated with specific entities, allowing a better categorization of NHL. However, these abnormalities are not as specific as initially described and their association is still unknown. DESIGN AND METHODS: By Southern blot and polymerase chain reaction, we have simultaneously analyzed the proto-oncogenes Bcl-1, Bcl-2, Bcl-6, c-myc and MLL and the tumor suppressor genes p53 and p16, in 100 unselected B-cell NHL patients at diagnosis, to establish its incidence throughout the different NHL subtypes, defined both by Working Formulation and REAL classifications, and to assess the frequency of co-existence of two or more genetic lesions within each individual patient. RESULTS: Fifty two cases displayed some genetic abnormality. Bcl-1, altered in 12 cases, was highly specific to mantle cell lymphomas (57% of them), but 6 cases had a different histologic subtype. Bcl-2 was rearranged in 26 cases: 70% in follicular lymphomas (FL) and 20% in diffuse large cell lymphomas; these abnormalities were also present in other subtypes, i.e. marginal lymphomas (30%). Bcl-6 abnormalities were mostly found in diffuse large cell lymphomas (29%) but also found in other subgroups, like FL (14%). C-myc rearrangements were specific to Burkitt's lymphoma. MLL gene was always germline. Deletions and/or rearrangements of p53 and p16 genes were rare (4% and 8% of all cases, respectively). Finally, association of genetic lesions was a relatively common finding (13% of cases), especially in cases with adverse prognostic morphologies according to the REAL. INTERPRETATION AND CONCLUSIONS: Molecular abnormalities are frequent in NHL at diagnosis, not only as unique lesions but also associated. A relative high specificity of some alterations was seen, thereby contributing to a better assessment of the histological subtype.