Influencia del flap en los resultados en la cirugía refractiva corneal con láser de femtosegundo: SMILE vs. FLEx / Influence of the flap on outcomes in corneal refractive surgery with femtosecond laser: SMILE vs. FLEx

OBJETIVO: Investigar la influencia de la creación de un flap corneal en la calidad óptica posquirúrgica en términos de predicción de la curvatura corneal y las aberraciones de Seidel tras 2modalidades de extracción lenticular corneal asistidas por láser de femtosegundo para la corrección de miopía y astigmatismo miópico: la técnica de extracción lenticular de pequeña incisión sin flap (SMILE) y la extracción lenticular con femtosegundo mediante la creación de un flap (FLEx). MÉTODOS: Estudio prospectivo consecutivo no aleatorizado comparativo de una serie de casos previamente intervenidos, incluyendo 64 ojos con un error refractivo de miopía y astigmatismo miópico. Los pacientes fueron divididos en 2grupos en función de la edad, sexo y miopía: un grupo tratado con SMILE y otro tratado con FLEx. Los valores de las aberraciones de Seidel root-mean-square fueron obtenidos en la visita preoperatoria y 3meses después de la cirugía con una apertura de 10mm usando el topógrafo ATLAS 9000. La relación entre el radio corneal posquirúrgico real y el radio pretendido fue analizada para cada uno de los grupos. RESULTADOS: El porcentaje medio de cambio en la curvatura corneal fue de −2,03% en el grupo FLEx y de −1,77% en el grupo SMILE (p = 0,655). La elevada correlación en el grupo SMILE muestra una predicción mejor después de la cirugía. Respecto a las aberraciones corneales, el tratamiento FLEx mostró un mayor incremento de las aberraciones de alto orden que el tratamiento SMILE (p = 0,04). CONCLUSIONES: El cambio refractivo medio en la curvatura corneal, indirectamente relacionado con la respuesta biomecánica de la superficie corneal tras el corte y extracción del lentículo, fue similar después de ambos tratamientos. Sin embargo, la técnica FLEx basada en la creación del flap mostró una mayor degradación en la calidad óptica corneal respecto a la inducción de aberraciones de alto orden

OBJECTIVE: To investigate the influence of creating a flap on the postoperative optical quality of the cornea in terms of predicted corneal curvature and Seidel aberrations after 2 modalities of femtosecond assisted corneal lenticule extraction laser for the correction of myopia and myopic astigmatism: The flapless procedure small incision lenticular extraction (SMILE) and the flap-based femtosecond lenticular extraction (FLEx). METHODS: The study is a prospective consecutive non-randomised comparative interventional case series including 64 eyes with myopic or myopic astigmatism refractive errors. Patients were divided into 2 groups matched for age, sex and myopia. One group underwent SMILE treatment and the other underwent FLEx treatment. Seidel aberrations root-mean-square values were obtained with a 10mm aperture using the ATLAS 9000 topographer before surgery and 3 months after surgery. The relationship between the post-surgical corneal radius and the predicted sculpted radius were analysed in each group. RESULTS: The mean percentage change in the curvature radius was −2.03% in the FLEx group and −1.77% in the SMILE group (P=.655). The higher correlation for the SMILE group demonstrates a better predictability after the surgery. As regards corneal aberrations, the FLEx treatment showed a greater increase of higher order aberrations than SMILE treatment (P=.04). CONCLUSION: The mean refractive change in corneal curvature, which is indirectly related to the biomechanical response of the corneal surface after the lenticule cut and extraction, was similar after both treatments. However, the flap based FLEx procedure showed a greater degradation of the corneal optical quality in terms of induction of higher order aberrations

Ovarian leiomyoma with myxoid stroma.

Ovarian smooth muscle tumours are rare. Notable myxoid change in smooth muscle tumours is uncommon, and raises diagnostic issues that need to be considered on evaluating a spindle cell lesion with notable myxoid change. There is only one case of myxoid leiomyoma of the ovary previously reported. We here report a case of ovarian leiomyoma with areas of myxoid stroma and discuss the relevant differential diagnosis and histological features to be assessed in such a lesion.

Influence of the flap on outcomes in corneal refractive surgery with femtosecond laser: SMILE vs. FLEx. / Influencia del flap en los resultados en la cirugía refractiva corneal con láser de femtosegundo: SMILE vs. FLEx.

OBJECTIVE: To investigate the influence of creating a flap on the postoperative optical quality of the cornea in terms of predicted corneal curvature and Seidel aberrations after 2 modalities of femtosecond assisted corneal lenticule extraction laser for the correction of myopia and myopic astigmatism: The flapless procedure small incision lenticular extraction (SMILE) and the flap-based femtosecond lenticular extraction (FLEx). METHODS: The study is a prospective consecutive non-randomised comparative interventional case series including 64 eyes with myopic or myopic astigmatism refractive errors. Patients were divided into 2 groups matched for age, sex and myopia. One group underwent SMILE treatment and the other underwent FLEx treatment. Seidel aberrations root-mean-square values were obtained with a 10mm aperture using the ATLAS 9000 topographer before surgery and 3 months after surgery. The relationship between the post-surgical corneal radius and the predicted sculpted radius were analysed in each group. RESULTS: The mean percentage change in the curvature radius was -2.03% in the FLEx group and -1.77% in the SMILE group (P=.655). The higher correlation for the SMILE group demonstrates a better predictability after the surgery. As regards corneal aberrations, the FLEx treatment showed a greater increase of higher order aberrations than SMILE treatment (P=.04). CONCLUSION: The mean refractive change in corneal curvature, which is indirectly related to the biomechanical response of the corneal surface after the lenticule cut and extraction, was similar after both treatments. However, the flap based FLEx procedure showed a greater degradation of the corneal optical quality in terms of induction of higher order aberrations.

Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in many cancer cells without causing toxicity in vivo. However, to date, TRAIL-receptor agonists have only shown limited therapeutic benefit in clinical trials. This can, most likely, be attributed to the fact that 50% of all cancer cell lines and most primary human cancers are TRAIL resistant. Consequently, future TRAIL-based therapies will require the addition of sensitizing agents that remove crucial blocks in the TRAIL apoptosis pathway. Here, we identify PIK-75, a small molecule inhibitor of the p110α isoform of phosphoinositide-3 kinase (PI3K), as an exceptionally potent TRAIL apoptosis sensitizer. Surprisingly, PI3K inhibition was not responsible for this activity. A kinome-wide in vitro screen revealed that PIK-75 strongly inhibits a panel of 27 kinases in addition to p110α. Within this panel, we identified cyclin-dependent kinase 9 (CDK9) as responsible for TRAIL resistance of cancer cells. Combination of CDK9 inhibition with TRAIL effectively induced apoptosis even in highly TRAIL-resistant cancer cells. Mechanistically, CDK9 inhibition resulted in downregulation of cellular FLICE-like inhibitory protein (cFlip) and Mcl-1 at both the mRNA and protein levels. Concomitant cFlip and Mcl-1 downregulation was required and sufficient for TRAIL sensitization by CDK9 inhibition. When evaluating cancer selectivity of TRAIL combined with SNS-032, the most selective and clinically used inhibitor of CDK9, we found that a panel of mostly TRAIL-resistant non-small cell lung cancer cell lines was readily killed, even at low concentrations of TRAIL. Primary human hepatocytes did not succumb to the same treatment regime, defining a therapeutic window. Importantly, TRAIL in combination with SNS-032 eradicated established, orthotopic lung cancer xenografts in vivo. Based on the high potency of CDK9 inhibition as a cancer cell-selective TRAIL-sensitizing strategy, we envisage the development of new, highly effective cancer therapies.

Differential expression of IL-8 and IL-8 receptors in benign, borderline and malignant ovarian epithelial tumours.

INTRODUCTION: Ovarian Cancer is the leading cause of death from gynecological malignancy. The poor prognosis is mainly due to presentation at a late stage and poor response to therapy. Much research is needed to identify diagnostic and prognostic biomarkers as well as therapeutic targets for ovarian cancer. Interleukin-8 is expressed by many tumour types and is known to have mitogenic, motogenic and angiogenic effects on tumour cells. AIMS: The aim of this study was to investigate the expression of IL-8 and IL-8 receptors (IL-8RA and IL-8RB) in different histological subtypes of ovarian tumours, as potential prognostic biomarkers in ovarian tumours. MATERIALS AND METHODS: Immunohitochemistry was used to study the expression of IL-8 and IL-8 receptors in 115 ovarian tumours including 21 benign tumours, 25 borderline tumours and 69 carcinomas of serous, clear cell, endometrioid and mucinous types. The correlation of expression profile, tumour type, stage, and progression free survival and overall survival was statistically analysed. RESULTS: IL-8 and IL-8 receptors were expressed in all types of tumours with variable intensity and subcellular distribution. There was a statistically significant correlation between levels of expression and tumour stage and tumour type, being mostly significant in serous tumours. No correlation with patient progression free survival or overall survival was found. CONCLUSION: This is the first study investigating the expression of IL-8 and IL-8 receptors using immunohistochemistry in different types of ovarian tumours, including benign and borderline tumours. IL-8 and IL-8RA are potential prognostic biomarkers and therapeutic targets in ovarian cancer, particularly in ovarian serous carcinoma.

An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study).

BACKGROUND: This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer. PATIENTS AND METHODS: Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3. RESULTS: Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 ≥50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders. CONCLUSIONS: Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.

Renal leiomyoma.

Renal leiomyomas are rare benign tumours, which are usually small in size and incidentally discovered in most of cases. We report a case of giant renal leiomyoma encasing the right kidney in a 55 year old lady. We review the spectrum of features seen in reported leiomyomas on imaging and gross appearance. We discuss the differential diagnosis and highlight the fact that renal leiomyoma, although rare, must be considered in the differential diagnosis of spindle cell lesions of the kidney and that this tumour may present as a huge renal mass.

CpG-island methylation study of liver fluke-related cholangiocarcinoma.

BACKGROUND: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. METHODS: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. RESULTS: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. CONCLUSION: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP.

The diagnostic accuracy of cervical biopsies in determining cervical lesions: an audit.

OBJECTIVE: The present audit was carried out to assess the diagnostic accuracy of cervical punch biopsy during colposcopy in comparison with diagnosis from subsequent cone excision. DESIGN AND SETTING: Retrospective analysis was performed by examining the histopathology reports for paired cervical punch biopsies and cervical cone excisions for cases reported from April 2004 to March 2005 (when cervical biopsies and cones were reported by general pathologists) and from January to December 2008 (when reporting by specialist gynaecological pathologists was instituted). SAMPLE: 150 women had both cervical punch and cone biopsies performed in the 2004-2005 period, while 149 women had both biopsies performed in 2008. MAIN OUTCOME MEASURES AND RESULTS: In 2004-5, the rate of consistent diagnosis was 68.7%, compared with 75.8% in 2008. This was due to a decrease in the rates of overdiagnosis (16.7% vs. 14.8%) and underdiagnosis (14.7% vs. 9.4%), which was statistically significant. The sensitivity rates for 2004-5 and 2008 were 87.5% and 89.7%, and the specificity rates for the same periods were 39.8% and 39.4% respectively. CONCLUSIONS: This audit highlights the importance of planning patient management on the basis of co-ordinated information from smear results, history, colposcopy findings and cervical biopsies. The introduction of specialist gynaecological histopathology reporting has significantly improved the rates of consistent diagnosis.

Alpha-fetoprotein-producing non-germ cell tumours of the female genital tract.

Elevated levels of alpha-fetoprotein (AFP), a foetal serum protein, occur mainly on the development of hepatocellular carcinoma (HCC) or germ cell tumours, including yolk sac tumour (YST) and embryonal carcinoma of the ovary. Rarely, other tumours of the female genital tract produce AFP. This article reviews the AFP-producing non-germ cell tumours reported in different parts of the female genital tract to date. These include different types of carcinomas and carcinosarcomas of the uterus, ovary and cervix and sex cord stromal tumours of the ovary. It is important for both pathologists and oncologists to be aware of such cases and the clinicopathological distinction from germ cell tumours, as the diagnosis would affect the management plan for the patient. The reviewed cases suggest that regardless of the patient's age when no lesion is detected in the liver and stomach of a woman whose serum AFP level is abnormally high, the female reproductive system should be examined as a possible site of AFP-producing tumour. Biochemical, physiological and pathological features of AFP are briefly presented.

Retroperitoneal solitary fibrous tumour arising from the pelvis in women--a case report and review of literature.

A solitary fibrous tumour is an unusual spindle cell neoplasm that most frequently occurs in the pleura based intrathoracic region. In recent years attention has been drawn towards solitary fibrous tumours arising in extrathoracic sites. They are usually benign but malignant solitary fibrous tumours have also been reported (Nielson et al. 1997). There is far less information about the clinical behaviour of an extra thoracic solitary fibrous tumour unlike intrathoracic tumours which is well reported in many case series (England et al. 1989). Although solitary fibrous tumours are well described lesions, the occurrence of similar tumours in the pelvic retroperitoneum of women and presenting as pelvic mass have been reported only sporadically. Because of the rarity, unpredictable behaviour; lack of information available about the clinical behaviour (recurrence and metastasis) and lack of follow up protocol, we are reporting this case which we encountered along with the review of previously reported cases.

Expression of beta-catenin in basal cell carcinoma.

Background beta-Catenin is a crucial member of the E-cadherin/catenin complex, which plays a major role in cell-cell adhesion. beta-Catenin is also known to be involved in signal transduction pathways. Many studies have demonstrated changes in the expression of beta-catenin in colorectal carcinomas, suggesting a role for beta-catenin in neoplastic development. Objectives Basal cell carcinoma (BCC) is a locally invasive tumour. The various subtypes show differences in biological behaviour. This study aimed to investigate the presence of differences in the immunoprofile of beta-catenin among histological variants of BCC. Methods Eighty BCCs were studied (32 nodular, 7 micronodular, 24 superficial and 17 infiltrative and morphoeic). Formalin-fixed, paraffin-embedded tissue sections were stained for beta-catenin using the avidin/biotin immunodetection technique. Results All the nodular BCCs showed membranous and weak cytoplasmic staining. Nuclear staining was seen in 15 of 32 (47%) cases, being stronger at the periphery of the nodules in 11 of 15 (73%) of these cases. In superficial BCCs the membranous staining was variable and cytoplasmic staining was increased. Nuclear staining was seen in 16 of 24 (67%) cases, being more notable at the periphery in 8 of 16 (50%) of these cases. All micronodular BCCs showed strong membranous staining, weak cytoplasmic and no nuclear staining. In the infiltrative and morphoeic BCCs membranous staining was completely lost at the advancing margins of the invading cell strands, with a marked increase in cytoplasmic staining; nuclear staining was observed in all these tumours. Conclusions The expression of beta-catenin varied between different types of BCC. Nuclear localization was most notable in the infiltrative and morphoeic variants, followed by the superficial variant, and seen least in nodular BCC. Its prominence at tumour margins suggests that this may be associated with more aggressive types of invasion.

The expression of E-cadherin and catenins in sporadic colorectal carcinoma.

The E-cadherin/catenin complex plays a major role in epithelial cell-cell adhesion. Immunohistochemical studies have highlighted perturbation in the expression and distribution of E-cadherin and catenins in sporadic colorectal neoplasms. In this study, we compared the expression of E-cadherin and catenins (alpha-, beta-, and gamma-catenin) in 30 sporadic colorectal carcinomas with that in the adjacent nonneoplastic mucosa and assessed whether any perturbation in the level of expression occurred at the messenger RNA (mRNA) or protein level. We also compared the expression of E-cadherin and catenins in 13 lymph node deposits and the primary tumors. Immunohistochemistry was used to study the level of expression and cellular distribution of E-cadherin and catenins. Levels of mRNA were studied by in situ hybridization. E-cadherin and catenin immunoreactivity was increased with cytoplasmic accumulation in more than 85% of the neoplasms. There were marked increases in the levels of mRNA in the carcinomas compared with the nonneoplastic mucosa. Nuclear localization of beta-catenin was higher at the invasive margin of some tumors, but expression of E-cadherin and catenin transcripts in the lymph node deposits showed no consistent relationship to that in the primary tumors.

E-cadherin and catenins: molecules with versatile roles in normal and neoplastic epithelial cell biology.

E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin, play a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of any of these molecules results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. The catenins are connected to many structural and functional proteins, which in turn influence their functions. Among these molecules are type 1 growth factor receptors, which along with other molecules are believed to alter the function of catenins through tyrosine phosphorylation. A recent finding is the association between the catenins and the adenomatous polyposis coli gene product (APC). APC mutation is an early event in colorectal carcinogenesis. It may possibly do so through perturbation of the critical cadherin/catenin complex. Further studies of the cadherin/catenin complex and its connections may give insight into the early molecular interactions critical to the initiation and progression oftumours, which should aid in the development of novel therapeutic strategies for both prevention and treatment.

Noninvasive vacuum constriction device in the management of erectile dysfunction.

The effectiveness of a device designed to overcome erectile impotence was assessed in 21 patients: 5 patients with vasculogenic impotence due to venous leakage, 6 with diabetes mellitus with or without atherosclerotic cardiovascular disease, 2 paraplegic patients after spinal cord injury, 3 severely obese patients and 5 patients with psychogenic impotence. They were instructed how to use the device, which uses suction to induce penile engorgement and maintains erection with a constriction band. A total of 17 patients (81%) achieved an erection or an erection-like state that was satisfactory for intercourse. No serious ill effect from the use of the device has been reported. In selected patients the device is an alternative to either surgical placement of penile prosthesis, intracavernous injection of vasoactive drugs or sexual abstinence.