Hysteroscopic outpatient metroplasty to expand dysmorphic uteri (HOME-DU technique): a pilot study.

The new classification system of uterine anomalies from the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy defines T-shaped and tubular-shaped infantilis uteri as 'dysmorphic'. Such malformations have been proven to be associated with poor reproductive performance. A prospective observational study was conducted with 30 infertile women with dysmorphic uterus who underwent the novel Hysteroscopic Outpatient Metroplasty to Expand Dysmorphic Uteri (HOME-DU ) technique. Incisions are made on the uterine walls with a 5 Fr bipolar electrode. The procedure was conducted in outpatients under conscious sedation, using a 5-mm office hysteroscope. The technique was successful in all cases without complications. A net increase of uterine volume was found, as measured at hysteroscopy and three-dimensional transvaginal ultrasound (P < 0.001). Uterine morphology improved in all patients but one. At mean follow-up of 15 months, clinical pregnancy rate was 57% and term delivery rate 65%. These early data support HOME-DU as safe and effective in expanding the volume and normalizing the appearance of the uterine cavity of dysmorphic uteri. Although the cohort was small, pregnancy and live births outcomes were favourable in this poor-prognosis group, implying desirable benefits, which should be compared with other techniques.

Thrombotic thrombocytopenic purpura during pregnancy versus imitator of preeclampsia.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organs due to a systemic endothelial cell injury secondary to a deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity. TTP is a rare complication of pregnancy with a poor prognosis and high fetal mortality, especially when it occurs during the first trimester. Recent data have supported that effective treatment of TTP is plasma therapy. Unfortunately a major problem remains in the delay in diagnosis due to confounding factors between other "imitators of preeclampsia." Rapid and readily available laboratory testing to quickly diagnose TTP is desperately needed to improve care and to save mother and future child life. CASE REPORT We describe a rare case of successful pregnancy after TTP manifestations occurring in the first trimester; most importantly, our experience represents the first case of atypical manifestation due to neurologic and kidney manifestations preceding laboratory assay alterations. RESULTS We treated a patient with plasma replacement of 30 mL/kg/day and daily plasmapheresis in combination with continuous infusion of fresh-frozen plasma 10 mL/kg/day. The response of clinical manifestation immediately improved. At 30 weeks, the patient had multiple episodes of high blood pressure and concomitant decrease of hemoglobin and platelet count, so a cesarean section was immediately performed. She delivered a healthy female baby. CONCLUSION Early diagnosis by ADAMTS13 activity, occasionally occurring before clinical manifestations, aided us in promptly administering commended and life-saving treatments.

Role of alternative interventional procedures when endo- and epicardial catheter ablation attempts for ventricular arrhythmias fail.

BACKGROUND Ventricular tachycardia (VT) refractory to antiarrhythmic drugs and standard percutaneous catheter ablation techniques portends a poor prognosis. We characterized the reasons for ablation failure and describe alternative interventional procedures in this high-risk group. METHODS AND RESULTS Sixty-seven patients with VT refractory to 4±2 antiarrhythmic drugs and 2±1 previous endocardial/epicardial catheter ablation attempts underwent transcoronary ethanol ablation, surgical epicardial window (Epi-window), or surgical cryoablation (OR-Cryo; age, 62±11 years; VT storm in 52%). Failure of endo/epicardial ablation attempts was because of VT of intramural origin (35 patients), nonendocardial origin with prohibitive epicardial access because of pericardial adhesions (16), and anatomic barriers to ablation (8). In 8 patients, VT was of nonendocardial origin with a coexisting condition also requiring cardiac surgery. Transcoronary ethanol ablation alone was attempted in 37 patients, OR-Cryo alone in 21 patients, and a combination of transcoronary ethanol ablation and OR-Cryo (5 patients), or transcoronary ethanol ablation and Epi-window (4 patients), in the remainder. Overall, alternative interventional procedures abolished ≥1 inducible VT and terminated storm in 69% and 74% of patients, respectively, although 25% of patients had at least 1 complication. By 6 months post procedures, there was a significant reduction in defibrillator shocks (from a median of 8 per month to 1; P<0.001) and antiarrhythmic drug requirement although 55% of patients had at least 1 VT recurrence, and mortality was 17%. CONCLUSIONS A collaborative strategy of alternative interventional procedures offers the possibility of achieving arrhythmia control in high-risk patients with VT that is otherwise uncontrollable with antiarrhythmic drugs and standard percutaneous catheter ablation techniques.

Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC)

Proteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix. However, they have an important role in the tumour development as well as in tumour progression. To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT-PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total). Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001). High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001). Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037). In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival. In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC. Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies.

Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome

Carcinoids are slow-growing neuroendocrine tumors that, in the lung, can be subclassified as typical (TC) or atypical (AC). To identify genetic alterations that improve the prediction of prognosis, we investigated 34 carcinoid tumors of the lung (18 TCs, 15 ACs, and 1 unclassified) by using array comparative genomic hybridization (array CGH) on 3700 genomic bacterial artificial chromosome arrays (resolution ?1 Mb). When comparing ACs with TCs, the data revealed: i) a significant difference in the average number of chromosome arms altered (9.6 versus 4.2, respectively; P = 0.036), with one subgroup of five ACs having more than 15 chromosome arms altered; ii) chromosomal changes in 30% of ACs or more with additions at 9q (?1 Mb) and losses at 1p, 2q, 10q, and 11q; and iii) 11q deletions in 8 of 15 ACs versus 1 of 18 TCs (P = 0.004), which was confirmed via fluorescence in situ hybridization. The four critical regions of interest in 45% ACs or more comprised 11q14.1, 11q22.1-q22.3, 11q22.3-q23.2, and 11q24.2-q25, all telomeric of MEN1 at 11q13. Results were correlated with patient clinical data and long-term follow-up. Thus, there is a strong association of 11q22.3-q25 loss with poorer prognosis, alone or in combination with absence of 9q34.11 alterations (P = 0.0022 and P = 0.00026, respectively).

Estrogen receptor β expression and androgen receptor phosphorylation correlate with a poor clinical outcome in hormone-naive prostate cancer and are elevated in castration-resistant disease

Patients with advanced prostate cancer (PC) are usually treated with androgen withdrawal. While this therapy is initially effective, nearly all PCs become refractory to it. As hormone receptors play a crucial role in this process, we constructed a tissue microarray consisting of PC samples from 107 hormone-naïve (HN) and 101 castration-resistant (CR) PC patients and analyzed the androgen receptor (AR) gene copy number and the protein expression profiles of AR, Serin210-phosphorylated AR (pAR(210)), estrogen receptor (ER)β, ERα and the proliferation marker Ki67. The amplification of the AR gene was virtually restricted to CR PC and was significantly associated with increased AR protein expression (P<0.0001) and higher tumor cell proliferation (P=0.001). Strong AR expression was observed in a subgroup of HN PC patients with an adverse prognosis. In contrast, the absence of AR expression in CR PC was significantly associated with a poor overall survival. While pAR(210) was predominantly found in CR PC patients (P<0.0001), pAR(210) positivity was observed in a subgroup of HN PC patients with a poor survival (P<0.05). Epithelial ERα expression was restricted to CR PC cells (9%). ERβ protein expression was found in 38% of both HN and CR PCs, but was elevated in matched CR PC specimens. Similar to pAR(210), the presence of ERβ in HN patients was significantly associated with an adverse prognosis (P<0.005). Our results strongly suggest a major role for pAR(210) and ERβ in HN PC. The expression of these markers might be directly involved in CR tumor growth.

Intratumoral hypoxia as the genesis of genetic instability and clinical prognosis in prostate cancer

Intratumoral hypoxia is prevalent in many solid tumors and is a marker of poor clinical prognosis in prostate cancer. The presence of hypoxia is associated with increased chromosomal instability, gene amplification, downregulation of DNA damage repair pathways, and altered sensitivity to agents that damage DNA. These genomic changes could also lead to oncogene activation or tumor suppressor gene inactivation during prostate cancer progression. We review here the concept of repair-deficient hypoxic tumor cells that can adapt to low oxygen levels and acquire an aggressive "unstable mutator" phenotype. We speculate that hypoxia-induced genomic instability may also be a consequence of aberrant mitotic function in hypoxic cells, which leads to increased chromosomal instability and aneuploidy. Because both hypoxia and aneuploidy are prognostic factors in prostate cancer, a greater understanding of these biological states in prostate cancer may lead to novel prognostic and predictive tests and drive new therapeutic strategies in the context of personalized cancer medicine.

Heterogeneity analysis of Metastasis Associated in Colon Cancer 1 (MACC1) for survival prognosis of colorectal cancer patients: a retrospective cohort study.

BACKGROUND Metastasis of colorectal cancer (CRC) is directly linked to patient survival. We previously identified the novel gene Metastasis Associated in Colon Cancer 1 (MACC1) in CRC and demonstrated its importance as metastasis inducer and prognostic biomarker. Here, we investigate the geographic expression pattern of MACC1 in colorectal adenocarcinoma and tumor buds in correlation with clinicopathological and molecular features for improvement of survival prognosis. METHODS We performed geographic MACC1 expression analysis in tumor center, invasive front and tumor buds on whole tissue sections of 187 well-characterized CRCs by immunohistochemistry. MACC1 expression in each geographic zone was analyzed with Mismatch repair (MMR)-status, BRAF/KRAS-mutations and CpG-island methylation. RESULTS MACC1 was significantly overexpressed in tumor tissue as compared to normal mucosa (p < 0.001). Within colorectal adenocarcinomas, a significant increase of MACC1 from tumor center to front (p = 0.0012) was detected. MACC1 was highly overexpressed in 55% tumor budding cells. Independent of geographic location, MACC1 predicted advanced pT and pN-stages, high grade tumor budding, venous and lymphatic invasion (p < 0.05). High MACC1 expression at the invasive front was decisive for prediction of metastasis (p = 0.0223) and poor survival (p = 0.0217). The geographic pattern of MACC1 did not correlate with MMR-status, BRAF/KRAS-mutations or CpG-island methylation. CONCLUSION MACC1 is differentially expressed in CRC. At the invasive front, MACC1 expression predicts best aggressive clinicopathological features, tumor budding, metastasis formation and poor survival outcome.

Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.