Histologic response after neoadjuvant chemoradiotherapy in locally advanced rectal adenocarcinoma: experience from Sudan.

Background: Locally advanced rectal cancer can be down staged by neoadjuvant therapy and the resultant tumor response can be quantified histologically. This study aimed to assess pathological response of neoadjuvant chemoradiation in patients with locally advanced rectal cancers treated in Wad Medani Teaching Hospital (WMTH) and National Cancer Institute (NCI), Wad Medani, Sudan. Patients and Methods: A total of 36 consecutive patients with locally advanced rectal cancer that were managed in WMTH and NCI during the period from 2006-2011 were reviewed. Preoperative pelvic radiotherapy was delivered. Total of 46 Gray were delivered concurrently with 5- fluorouracil (5-FU) on the first and last week of radiation. Total mesorectal excision of the rectal tumour either by anterior or abdominoperineal resections was planned at 6-8 weeks from completion of preoperative treatment. The pathological response to therapy was assessed by histopathology examination of the surgical specimen. Results: Initial clinical staging of patients revealed 58.3% of them were stage T3/T4N2M0 and 41.7% were stage T3N0M0. Down-staging to stage T1/T2N0M0 was found in 36.1% and stage T3N0M0 in 30.6%. No response was seen in 8.3% of cases with stage T3/T4N2M0 while complete clinical response (no residual) was seen in 25.0%. Complete histological response was observed in 13.8%. Positive lymph-nodes metastasis was confirmed in 8.3% of cases. Conclusion: Neoadjuvant chemoradiation is a reasonable option for cases of rectal cancer and deserves further evaluation.

Valor de la histeroscopia en el diagnóstico del adenocarcinoma de endometrio

156 p.

Pancreatectomía córporo-caudal con resección del tronco celíaco por adenocarcinoma de cuerpo pancreático: intervención de Appleby modificada

La resección oncológica completa es el único procedimiento que permite la sobrevida a largo plazo en cáncer de páncreas. La afectación de la arteria hepática, tronco celíaco o arteria mesentérica superior constituyen una contraindicación quirúrgica porque se asocia a mal pronóstico y por las dificultades técnicas que implica conseguir la resección oncológica completa. Solo un grupo seleccionado de pacientes con buena respuesta a la quimioterapia y pasibles de resección R0 se benefician de la cirugía de resección del tronco celíaco. A partir de un caso clínico de un adenocarcinoma de páncreas con infiltración de la arteria hepática común y tronco celíaco que tras una buena respuesta a la neoadyuvancia y embolización de la arteria hepática común fue sometido a una esplenopancreatectomía córporo-caudal con resección del tronco celíaco, se realiza una revisión de la literatura sobre el tema y sus aspectos técnicos relevantes. El análisis realizado permite sugerir que en casos debidamente seleccionados la pancreatectomía córporo-caudal con resección del tronco celíaco en bloque es un procedimiento factible, seguro, y con buenos resultados quirúrgicos y oncológicos. En condiciones de respuesta a la quimioterapia neoadyuvante y experiencia del equipo quirúrgico pareciera que esta cirugía podría mejorar el pronóstico y calidad de vida de estos enfermos.

Adenocarcinoma pleomórfico de células giganates de vías biliares(osteoclastoma like)

Las células gigante tipo osteoclásticas (CGTO) del páncreas son una entidad poco frecuente descrito originalmente por Rosaien 1968, caracterizado por osteoclastos, que son células gigantes mononucleares idénticas a las células del estroma observadas en tumores óseos. Desde entonces, hay pocos informes de los tumores que contienen células gigantes en otras localizaciones anatómicas. Las CGTO se pueden distinguir de las células gigantes tipo pleomórficas (CGTP), debido a la falta de un marcado pleomorfismo nuclear asociado. A menudo, un carcinoma de páncreas histológicamente reconocibles acompaña CGTO, dando lugar a un mal resultado. Formas puras de CGTO presentan un mejor pronóstico porque se necesita mucho tiempo para desarrollar metástasis, pero esta forma es muy raros, con pocos casos reportados en la literatura Inglésa. La mayoría de veces se discute el diagnóstico de benignidad de estos tumores basados en la evaluación de inmunohistoquímica. El presente caso se trata de una paciente de sexo femenino de 56 años de edad con cuadro caracterizado por dolor tipo cólico que mejora con antiespasmódicos, de varios meses de evolución, con periodos de remisión y exacerbación. A examen físico presenta: en piel y mucosas ligero tinte subictérico, a nivel abdominal: abdomen doloroso de forma difusa sin viseromegalias o masas palpables

Grief elaboration of a patient with a diagnosis of advanced colon adenocarcinoma: a case study

Objective: The term grief, from the French term grever, which means “to burden, to oppress”, can be deined as the process through which a person must go due to the loss of a loved one. We present a case of grief elaboration in a patient and his family that face a terminal illness. Clinical case: The patient is a 51-year-old man diagnosed with stage T4a N2b M1 colon adenocarcinoma. He came to the Department of Psycho-Oncology presenting depressive symptoms, marital and family issues associated with a medical condition, and work related issues. Conclusions: The patient was diagnosed with a secondary major depressive disorder episode in reaction to his medical condition. He was prescribed anti-depressive treatment, and family psychotherapy was recommended for grief elaboration.

"¡Andá a hilar la lana!" : La construcción del ideal femenino en los fragmentos 618-9 y 681 M de Lucilio a la luz de los intertextos

En la Antigua Roma las mujeres casadas no gozaban de ningún tipo de libertades y todos los placeres les eran vedados a su clase (Rousselle, 2000). Responsables de la gestación de los futuros ciudadanos, su esfera de acción se limitaba al hogar, donde, además de procurarles especial atención a sus maridos e hijos, estaban encargadas de realizar, entre otras tareas, el control de la servidumbre, la administración de los gastos y el tejido (Knapp, 2011). A diferencia de las mujeres de otras clases, prostitutas y esclavas, la conducta de las matronas debía estar regida por la castidad, la reserva, la modestia y la pietas, principales virtudes celebradas en las fuentes epigráficas (CIL 6.23773, 8.11294). Como consecuencia de la corrupción de las costumbres durante la República, Augusto sancionó una serie de leyes (Lex Iulia de maritandis ordinibus y de adulteriis coercendis en 18 a.C., Lex Papia Poppaea en 9 d.C.) que, basándose en la tradición de los antepasados, estaban destinadas a ejercer un fuerte dominio sobre las políticas familiares. Se obligaba a los estratos superiores de la sociedad a contraer uniones legítimas y a tener descendencia, y se sancionaba con severidad a aquellas mujeres que cometían adulterio y que no se ajustaban al modelo femenino que el Estado buscaba imponer (Pomeroy, 1999). Bajo la luz de estas consideraciones acerca de la matrona, nos proponemos ofrecer una lectura posible de los fragmentos 618-9 y 681 M del poeta satírico Lucilio, conservados únicamente por transmisión indirecta. Así pues, a partir de información recabada del contexto social y político, intentamos demostrar que en el horizonte del pensamiento romano se mantiene constante un único ideal de mujer, al mismo tiempo que, a partir de referencias intertextuales, logramos dar sentido(s) a un texto que sólo a simple vista parece no poder decirnos mucho

"¡Andá a hilar la lana!" : La construcción del ideal femenino en los fragmentos 618-9 y 681 M de Lucilio a la luz de los intertextos

En la Antigua Roma las mujeres casadas no gozaban de ningún tipo de libertades y todos los placeres les eran vedados a su clase (Rousselle, 2000). Responsables de la gestación de los futuros ciudadanos, su esfera de acción se limitaba al hogar, donde, además de procurarles especial atención a sus maridos e hijos, estaban encargadas de realizar, entre otras tareas, el control de la servidumbre, la administración de los gastos y el tejido (Knapp, 2011). A diferencia de las mujeres de otras clases, prostitutas y esclavas, la conducta de las matronas debía estar regida por la castidad, la reserva, la modestia y la pietas, principales virtudes celebradas en las fuentes epigráficas (CIL 6.23773, 8.11294). Como consecuencia de la corrupción de las costumbres durante la República, Augusto sancionó una serie de leyes (Lex Iulia de maritandis ordinibus y de adulteriis coercendis en 18 a.C., Lex Papia Poppaea en 9 d.C.) que, basándose en la tradición de los antepasados, estaban destinadas a ejercer un fuerte dominio sobre las políticas familiares. Se obligaba a los estratos superiores de la sociedad a contraer uniones legítimas y a tener descendencia, y se sancionaba con severidad a aquellas mujeres que cometían adulterio y que no se ajustaban al modelo femenino que el Estado buscaba imponer (Pomeroy, 1999). Bajo la luz de estas consideraciones acerca de la matrona, nos proponemos ofrecer una lectura posible de los fragmentos 618-9 y 681 M del poeta satírico Lucilio, conservados únicamente por transmisión indirecta. Así pues, a partir de información recabada del contexto social y político, intentamos demostrar que en el horizonte del pensamiento romano se mantiene constante un único ideal de mujer, al mismo tiempo que, a partir de referencias intertextuales, logramos dar sentido(s) a un texto que sólo a simple vista parece no poder decirnos mucho

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Spatiotemporal investigations of DNA damage repair using microbeams

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organisation is still unclear despite its decisive role in determining the fate of the damaged cell. Revealing the dynamic sequence of the repair proteins is therefore critical in understanding how the DNA repair mechanisms work. There are also still open questions regarding the possible movement of damaged chromatin domains and its role as trigger for lesion recognition and signalling in the DNA repair context. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. We have followed the development of radiation-induced foci for three DNA damage markers (i.e. γ-H2AX, 53BP1 and hSSB1) using normal fibroblasts (AG01522), human breast adenocarcinoma cells (MCF7) and human fibrosarcoma cells (HT1080) stably transfected with yellow fluorescent protein fusion proteins following irradiation with the QUB X-ray microbeam (carbon X-rays <2 µm spot). The size and intensity of the foci has been analysed as a function of dose and time post-irradiation to investigate the dynamics of the above-mentioned DNA repair processes and monitor the remodelling of chromatin structure that the cell undergoes to deal with DNA damage.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early stage endometrial cancer

Objectives: To evaluate the clinical value of pre-operative serum CA125 in predicting the presence of extra-uterine disease in patients with apparent early stage endometrial cancer. Methods: Between October 6, 2005 and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. This study is based on data from 657 patients with endometrial adenocarcinoma who had a pre-operative serum CA125 value, and was undertaken to correlate pre-operative serum CA125 with final stage. Results: Using a pre-operative CA-125 cutpoint of 30U/ml was associated with the smallest misclassification error (14.5%) using a multiple cross-validation method. Median pre-operative serum CA-125 was 14U/ml, and using a cutpoint of 30U/ml, 14.9% of patients had elevated CA-125 levels. Of 98 patients with elevated CA-125 level, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had elevated CA-125 level. In univariate and multivariate logistic regression analysis, only pre-operative CA-125 level was found to be associated with extra-uterine spread of disease. Utilising a cutpoint of 30U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0%, 88.5%, 36.7% and 85.7% respectively. Overall, 326/657 (49.6%) of patients had full surgical staging involving lymph node dissection. When analysis was limited to patients that had undergone full surgical staging, the outcomes remained essentially unchanged. Conclusions: Elevated CA-125 above 30U/ml in patients with apparent early stage disease is associated with a sensitivity of 31.0% and specificity of 88.5% in detecting extra-uterine disease. Pre-operative identification of this risk factor may assist to triage patients to tertiary centres and comprehensive surgical staging.

Targeting aurora kinases : a novel approach to curb the growth and chemoresistance of androgen refractory prostate cancer

Aurora Kinase (AK) based therapy targeting AK-A & B is effective against some cancers. We have explored its potential against previously unreported incurable, metastatic androgen depletion independent Prostate Cancer (ADIPC). We used androgen sensitive (AS) and ADI lines derived from Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. The relevance of this model was unequivocally established through focussed array, quantitative PCR and western blotting studies; significantly greater alteration of genes (fold change and number) representing major cancer pathways was shown in ADI cells compared to AS lines. A marked enhancement of in vivo growth of the ADI subline showing the greatest degree of gene modulations [TRAMP C1 (TC1)-T5: TC1-T5] reflected this. In contrast to the parental AS TC1 line, TC1-T5 cells grew with 100% incidence in the prostate, as lung pseudometastases and migrated to the bone and other soft tissues. The potential involvement of AKs in this transition was indicated by the significant upregulation of AK-A/B and their downstream regulators, survivin and phosphorylated-histone H3 in TC1-T5 cells compared to TC1 cells. This led to enhanced sensitivity of TC1-T5 cells to the pan-AK inhibitor, VX680 and to significant reduction in in vivo tumour growth rates when AK-A and/or B were downregulated in TC1-T5 cells. This cell growth inhibition was markedly enhanced when both AKs were downregulated and also led to substantially greater sensitivity of these cells to docetaxel, the only chemotherapeutic with activity against ADI PC. Finally, use of VX680 with docetaxel led to impressive synergies suggesting promise for treating clinical ADI metastatic PC.

Association between ambient ultraviolet radiation and risk of esophageal cancer

OBJECTIVES: Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. METHODS: We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. RESULTS: Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. CONCLUSIONS: These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.

Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29

Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16 (CA16). However some HFMD caused by EV71 may further develop into severe neurological complications such as encephalitis and meningitis. The route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular fluid or droplet from the infected or via faecal-oral route. To this end, this study utilised a human colorectal adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was first detected in HT29 cells as early as 12 h post infection (hpi) while viral protein was first detected at 48 hpi. A significant change in HT29 cells’ morphology was also observed after 48 hpi. Furthermore HT29 cell viability also significantly decreased at 72 hpi. Together, data from this study demonstrated that co-culture of HT29 with EV71 is a useful in vitro model to study the pathogenesis of EV71

Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.