Septo-optic dysplasia: Ophthalmological abnormalities in a series of 5 cases.

Septo-optic dysplasia (SOD) is a rare congenital condition of unknown cause, with a characteristic triad that includes optic nerve hypoplasia, pituitary function abnormalities and midline brain defects, in addition to a broad spectrum of symptoms and associations. A total of five clinical cases are presented, four of which met the complete classic triad. All of them showed a wide variety of ophthalmological, endocrinological and neurological alterations. Within the ophthalmological spectrum of SOD, papillary hypoplasia and ocular motility alterations (nystagmus, strabismus) stand out. Other less frequent ones may also appear, such as pupillary alterations, microphthalmia and coloboma. Given the suspicion of SOD, brain MRI scan should be performed, as well as consultation with the paediatric department in order to complete the study and indicate, if necessary, systemic treatment.

[Hematuria as the first sign of pelvic chondrosarcoma]. / Hematuria como primer signo del condrosarcoma de pelvis.

Chondrosarcoma is a malignant tumor which often affects the pelvic ring and its symptomathology is non-specific and insidious. We display a case of a right iliopubic branch chondrosarcoma in a 62-year-old male whose first sing was a four-year history of sporadic macroscopic haematuria, related to efforts. After being studied by the Urology Department by cystoscopy and biopsy of bladder tumor, chondral cells were appreciated. Further study with imaging tests diagnosed low-grade chondrosarcoma with bladder infringement. The case is assessed by Musculoskeletal Tumors Committee and a multidisciplinary approach is carried out through en bloc resection and pelvic floor reconstruction. Currently the patient remains asymptomatic.

El condrosarcoma es un tumor maligno que afecta con frecuencia la pelvis y su sintomatología es inespecífica e insidiosa. Describimos el caso de un condrosarcoma de la rama iliopubiana derecha en un varón de 62 años cuyo primer signo de aparición fue una hematuria macroscópica esporádica, relacionada con esfuerzos y de cuatro meses de evolución. Tras ser estudiado por el servicio de urología mediante cistoscopía con biopsia de tumoración en pared vesical se aprecian células de estirpe condral. Tras posterior estudio con pruebas de imagen se diagnostica condrosarcoma de bajo grado con invasión de la vejiga, por lo que es valorado en el comité de tumores musculoesqueléticos y se realiza un abordaje multidisciplinar mediante exéresis en bloque y reconstrucción del suelo pélvico. Actualmente el paciente continúa asintomático.

Efficacy and safety of immune checkpoint inhibitor immunotherapy in elderly cancer patients.

PURPOSE: There is limited evidence on the efficacy and safety of anti-programmed cell death protein 1 (PD-1)-/anti-programmed death-ligand 1 (PD-L1)-based immunotherapy in the elderly, particularly those aged over 75 years. METHODS/PATIENTS: The clinical response and toxicity profile of anti-PD-1-/anti-PD-L1-based immunotherapy in patients aged over 75 years were assessed in this retrospective observational study conducted in the Medical Oncology Service of a tertiary level hospital. The associations among clinical responses, adverse events, and geriatric syndromes were evaluated. RESULTS: In total, 20 patients aged between 75 and 94 years were evaluated. Pembrolizumab and nivolumab were the most commonly used drugs. A clinical benefit (stable disease, partial response or complete response) was documented in 13 patients (65%). This proportion was 80% in patients aged between 75 and 79 years, and 50% in those aged over 79 years (p = 0.236). The adverse events were similar to those reported in younger patients. At least one clinical adverse event (cAE) and one laboratory adverse event (lAE) was reported in 75% and 55% of patients, respectively. Polypharmacy was observed for all patients and multi-morbidity in 95%. Patients without gait disorders showed more responses to immunotherapy. The number of lAEs was significantly associated with the number of commonly prescribed drugs (slope = 0.218, p = 0.010), the Eastern Cooperative Oncology Group score, and the number of cAEs. CONCLUSIONS: The elderly can obtain benefits from anti-PD-1-/anti-PD-L1-based immunotherapy. The toxicity profile was similar to that reported in younger counterparts.

Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial.

BACKGROUND: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. PATIENTS AND METHODS: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. RESULTS: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. CONCLUSIONS: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations. CLINICALTRIALS.GOV NUMBER: NCT01704703. EUDRACT NUMBER: 2012-001955-38.

Gastric cancer epidemiology in tertiary healthcare in Chiapas. / Epidemiología de cáncer gástrico en el tercer nivel de atención en salud en Chiapas.

INTRODUCTION AND AIM: Gastic cancer is the most frequent neoplasia of the digestive tract worldwide. Incidence rates vary according to the region or country analyzed. Variation in the different regions of Mexico is attributed to very specific dietary, environmental, and genetic patterns. The aim of the present work was to carry out an epidemiologic analysis of the cases of gastric cancer treated at the Hospital Regional de Alta Especialidad 'Ciudad Salud', located in Chiapas, Mexico. MATERIAL AND METHODS: A descriptive, ambispective, longitudinal study was conducted. Cases of gastric cancer were searched for in the database from the oncology service of our hospital, that were treated within the time frame of 2007 to 2014. The data obtained were analyzed using the SPSS v. 20 statistics program. RESULTS: A total of 100 cases of gastric cancer were detected, 84 of which were included in the study. Forty-one of the cases were men, 43 were women, and their mean age was 57.3 years. Incidence was 2.14 for every 100 oncology patients released from the hospital. Of the study patients, 35.71% stated they had been alcoholics, 22.61% were smokers, and 90.16% were diagnosed with adenocarcinoma. At the end of follow-up, 18 of the study patients had died. CONCLUSION: The results of the present epidemiologic analysis showed that the consumption of alcohol and tobacco played an important role in the development of gastric cancer in the patients studied, as well as having a family history of any type of cancer. Because gastric cancer is usually diagnosed in advanced stages, it would be reasonable to formulate a strategy for the prevention, early detection, and control of the disease in the State of Chiapas, Mexico.

Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy. PATIENTS AND METHODS: A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue. RESULTS: ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 - 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 - 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%. CONCLUSIONS: Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.

Direct electrical bipolar electrostimulation for functional cortical and subcortical cerebral mapping in awake craniotomy. Practical considerations.

INTRODUCTION: The aim of brain glioma surgery is to maximize the quality of resection, while minimizing the risk of sequelae. Due to the frequent location of gliomas near or within eloquent areas, owing to their infiltrative feature, and because of major interindividual variability, the anatomofunctional organization and connectivity must be studied individually. Therefore, to optimize the benefit-to-risk ratio of surgery, intraoperative functional mapping is extensively used. MATERIAL AND METHODS: This article aims at describing the rationale, indications and practical aspects of intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions using the asleep-awake asleep anaesthetic protocol in the setting of cerebral gliomas. We will address the operative approach, including patient positioning, functional mapping resection strategy, anaesthetic conditions, as well as tips and pitfalls. RESULTS: The intraoperative direct electrical bipolar electrostimulation enables: (i) to study the real-time individual cortical functional organization; (ii) to study the anatomofunctional subcortical connectivity along the resection; (iii) to tailor the resection according to individual corticosubcortical functional boundaries. This is an easy, accurate, reliable, well-tolerated and safe detection technique of both cortical and subcortical functionally essential structures during resection. It should be performed in the context of a standardized protocol involving members of both anaesthesiology and neurosurgery teams at neurosurgical centers specialized in surgical neuro-oncology. CONCLUSION: Intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions is currently considered the "gold standard" clinical tool for brain mapping during cerebral resection in neuro-oncology.

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

Long-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM.

[Outcomes after operative treatment of distal radius fractures - an analysis of 721 patients]. / Ergebnisse der operativen Versorgung distaler Radiusfrakturen - eine Analyse von 721 Patienten.

AIM OF THE STUDY: Treatment strategies in distal radius fractures differ nationally and internationally. Conservative and operative treatment options compete as well as implants, postoperative therapy regimens and the necessity of implant removal. In our institution operative treatment is favoured. In the following the results of 721 surgically treated patients are presented. PATIENTS: PATIENTS who underwent operative treatment of their distal radius fractures in our institution between 2008 and 2011 were retrospectively analysed. Following patient characteristics have been surveyed regarding age, sex, location of plate osteosynthesis, operation time, time of cast immobilisation and complications like infections, tendon ruptures, need of revision surgery. RESULTS: 721 patients (mean age: 59.03 years) were retrospectively analysed. 514 of them (71.29 %) were female. Time of operation was after a mean duration of 5.48 days. In 558 (77.39 %) patients we performed palmar plate osteosynthesis. 89 (12.34 %) had dorsal plate osteosynthesis and 74 (10.3 %) cases were treated with either K-wires or screws. 18 (2.5 %) patients had concomitant traumatic carpal tunnel syndrome and a concomitant SL rupture was seen in 38 (5.27 %) patients. 40 (5.55 %) patients underwent operative revision because of posttraumatic carpal tunnel syndrome (n = 15), tendon ruptures (n = 7), malposition of screws (n = 6), loss of reduction (n = 6) and infection (n = 3). Mean duration of in-hospital stay after operation was 6.6 days. Implant removal was performed in 77 (10.7) patients; 59 (8.2 %) patients had palmar plate osteosynthesis and 18 (2.5 %) patients had dorsal plating. CONCLUSION: Because of the low complication rate after operative treatment of distal radius fractures, osteosynthesis of this fracture seems to be warranted. Regarding the patients' higher age we have seen an unexpectedly long in-hospital stay with a mean time of 6.6 days. Herein attempts should be made to reduce time of in-hospital stay. In our opinion implant removal should not be recommended routinely.

[TVA and TOA. New adjustable mesh for the treatment of female stress incontinence. Preliminaries results]. / TVA y TOA. Nuevas mallas ajustables de tensión en el tratamiento de la incontinencia urinaria de esfuerzo. Resultados preliminares.

OBJECTIVES: Evaluation of a new mesh for incontinence (TVA/TOA) which enables the degree of tension applied during surgery to be readjusted at the post-operative stage. PATIENTS AND METHOD: 62 patients treated with the TVA mesh and monitored over a 14-month period (SD 7.8, range 6-38). In 33 patients (53%) some other pelvic prolapse was corrected. Evaluation was carried out by clinical report, examination of bladder full of 250 saline solution, flowmetry and urinary residue. 40 patients filled in 4 quality of life questionnaires (QoL; ICIQ-SF; PGI-S; PGI-I). RESULTS: 42 patients were found to be objectively continent in the post-operative evaluation. Of these, it was necessary to reduce tension in 7 cases (11%) due to urinary obstruction (flow < 10 ml/sec and/or residue). The tension of the mesh was tightened in 20 patients (32%) due to continue with a certain degree of incontinence. All patients were discharged as continent and with no residue. In the last revision, 58 patients (93%) proved to be objectively continent and 4 (6.5%) showed a notable improvement in their incontinence. The Q(MAX) is 19.8 ml/sec (SD 9.8). The mictional urgency had disappeared or improved in 32 of the patients who had this prior to operation (76%) and had appeared in 3 of the patients who didn't (15%). The clinical report showed a high level of consensus with the ICIQ-SF survey (Kappa = 0.89) regarding stress incontinence, diminishing clearly (Kappa= 0.13) when urge incontinence was taken into account. 34 (85%) patients scored over 95 out of 110 in the QoL. 30 (75%) scored less than 6 in ICIQ-SF. 32 (80%) showed a perception of normality and 4 (10%) slight illness in the PGI-S. In the PGI-I 29 (72.5%) were much better and 11 (27.5%) quite a lot better. A relation exists between urgency and dismissed quality of life. CONCLUSION: With the TVA (trans-vaginal adjustable) mesh it is possible to adjust the tension originally applied during surgery at the post-operative stage, so that any defects or excesses can be corrected.

Insulin-like growth factor I is required for vessel remodeling in the adult brain.

Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1 alpha and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum/brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction.

From transcription to cell surface expression, the induction of MHC class II I-A alpha by interferon-gamma in macrophages is regulated at different levels.

Using mouse bone marrow-derived macrophages we determined the role of interferon (IFN)-gamma at the different steps in expression of the I-A alpha chain of MHC class II molecules, from transcription to the cell surface. Levels of transcription, RNA, and protein were low in cells not stimulated with IFN-gamma. Treatment with IFN-gamma for 24 or 48 h induced an increase in mRNA levels (7- and 12-fold) that did not correlate with the increase in transcription (2.5- and 2.7-fold). The half-life of mRNA was not modified by IFN-gamma. These data suggest a block at the level of translation. In fact, IFN-gamma increased ribosome loading, which confirms regulation at the translational level. Treatment with IFN-gamma increased protein synthesis (6-fold after 48 h) and level of expression at the cell surface (3- and 9-fold after 24 and 48 h, respectively). Interestingly, treatment with IFN-gamma also increased the I-A alpha protein half-life from 2 to 6-7 h. This is the first attempt to determine qualitatively and quantitatively the regulation of an inducible gene at all the putative levels of control. The data indicate that IFN-gamma plays a critical role in MHC class II protein expression in macrophages through the regulation of different steps, from transcription to surface expression.

[Histologic regression of localized prostatic tumor with neoadjuvant hormonal therapy]. / Desaparición histológica del tumor prostático localizado con hormonoterapia neoadyuvante.

OBJECTIVES: To determine the usefulness of preoperative hormone therapy in patients with organ-confined prostatic carcinoma undergoing radical prostatectomy. METHODS: 7 patients with localized prostatic carcinoma are presented. All patients were submitted to radical prostatectomy; 4 had been randomly selected for preoperative hormone therapy. RESULTS: Histological examination showed no nodal involvement in all cases. The tumor could not be identified (Po) in two of the four patients who received hormone therapy. The other two patients were staged down; the Gleason score remained unchanged in one and increased in the other. The patients who did not receive preoperative hormone therapy showed concordant clinical and pathological stages, except one in whom infiltration of the prostatic capsule was observed. No difference was found concerning the facility in performing surgery between the treated and untreated patients. CONCLUSIONS: Hormonal deprivation eliminated the tumor burden in two cases that might have been completely hormone sensitive, with no correlation in the pretreatment histological grade. Clinical downstaging is achieved by this treatment modality. However, further studies in larger series comparing the percentages of downstaging, histological downgrading, absence of tumor cells in the surgical specimen and impact on survivorship are warranted.

[Prediction of continence in patients with neurogenic bladder who will be treated with bladder augmentation]. / Predicción de la continencia en pacientes con vejiga neurógena a quienes se va a realizar una ampliación vesical.

Twenty four patient with neurogenic bladder undergoing vesical enlargement were pre-operatively evaluated to determine the need to perform also an anti-incontinence technique. None of them had such a technique performed, so as to control whether our prediction was correct. Each patient had one or more video-urodynamic studies performed to evaluate adjustment and the likely vesical hyperreflexia, critical incontinence pressure, and the presence of leaks with cough and cervicourethral morphology at different filling times. Critical incontinence pressure and presence of contrast leaks with cough, the latter demanded with moderate intravesical pressures, have been the parameters which better predicted the likely incontinence, with reliability over 90%. With regard to myelodysplastic bladders, the study shows the relevance of the detrusor as a cause of incontinence and sustains the practice of implementing only the cervical cuff without the remaining components when the artificial sphincter is chosen as the anti-incontinence technique, when the likely cause, whether sphincter or detrusor, is unclear at the time of considering vesical enlargement.

[Renal and urinary tract leishmaniasis. A disease to keep in mind]. / Leishmaniasis renal y vías urinarias. Patología a tener en cuenta.

Report of a case of renal and urinary tract leishmaniasis in a 61-year old male patient. The ureteral lesion responded favourably to treatment, unlike the renal one which required conservative surgery. Review of the literature stressing the fact that no other case has been found of kidney and urinary tract involvement. It is concluded that in the future, at least in those areas with a high prevalence of leishmaniasis, this condition should be taken into account as differential diagnosis when facing a toxic picture with renal involvement of the calyceal ecstasies type.

[Retroperitoneal paraganglioma. Infrequent pathology]. / Paraganglioma retroperitoneal. Patología poco frecuente.

Presentation of 3 cases of retroperitoneal paraganglioma non pre-operatively diagnosed: one dependent of the Zuckerkandl's organ with ultrasound examination showing a panelled cystic mass, and two located in the renal parahilar area, all accidental findings during renal surgery. Lack of appropriate pre-operative background and diagnosis produced a hypertensive crisis in one patient during removal manoeuvres which was entirely controlled. After a 4-, 2- and 1-year follow-up, respectively, patients remain asymptomatic and disease-free. An analysis of the most relevant features in these retroperitoneal tumorations was carried out from a clinical, diagnostic, therapeutic and prognostic point of view.

[Primary amyloidosis in the bladder: diagnostic and therapeutic update]. / Amiloidosis primaria de localización vesical: actualización diagnóstica y terapéutica.

We describe an additional case of primary amyloidosis of the bladder whose form of presentation warranted a differential diagnosis from carcinoma of the bladder. The diagnosis was made on the histological findings and the immunohistochemical analyses revealed amyloid fibrils that reacted against the light chain lambda antiserum. The treatment of choice was TUR, which resolves the condition in most of the cases. Conservative surgery, however, does not prevent new deposits and undetected residual lesions may persist, which may warrant other complementary procedures in these patients. After the diagnosis has been made, it is important to discard systemic amyloidosis.

[New location of aggressive angiomyxoma: the bladder]. / Nueva localización del angiomixoma agresivo: la vejiga.

Presentation of one case of aggressive angiomyxoma with vesical location in a 31-year-old female patient who underwent partial surgery, and who 8 years later remains disease-free. Emphasis is made on the low frequency of these tumours, of which only 26 cases are described in the international literature. All these cases have been located in soft areas of the pelvis and the perineum, with the exception of the one presented here, the first one with a vesical location. Clinical behaviour is characterized by the absence of metastasis and a great tendency to local relapse, 70% of cases reported.