Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.

A prospective observational study of the clinical and pathological impact of stereotactic body radiotherapy (SBRT) as a neoadjuvant strategy of chemoradiation in pancreatic cancer.

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.

Management of hyperbilirubinaemia in pancreatic cancer patients.

Development of hyperbilirubinaemia is common in patients with advanced pancreatic adenocarcinoma, both at diagnosis as well throughout disease evolution. For this reason, hyperbilirubinaemia determines chemotherapy treatment selection, and therefore it should be considered one of the most relevant conditions. There is very little evidence for the use of chemotherapy in this setting. This article summarises the main causes of hyperbilirubinaemia, how to treat them as well as their differential diagnosis. The current clinical evidence of the available drugs as well as the recommendations of use different combinations in the context of hyperbilirubinaemia are also reviewed.

Lymphocytic interstitial pneumonitis (LIP)-the liver and the lung.

Chronic liver disease may involve the lung through abnormal communications between the portal and pulmonary veins or by changes in the lungs caused by similar biochemical abnormalities to those in liver parenchyma. Lymphocytic interstitial pneumonitis(LIP) is more common in women and is associated with autoimmune diseases. Chest x-ray findings include reticular or reticulonodular opacities while computed tomography (CT) usually shows subpleural fibrosis (predominately in basal areas), ground-glass attenuation, traction bronchiectases and pulmonary parenchymal cysts.

The value of conjunctival biopsy in childhood cystinosis.

Cystinosis is frequently presented with cystine storage in the cornea and conjunctiva, and the diagnosis can be established by slit-lamp examination. It can also be confirmed by electron microscopy of a conjunctival biopsy. The present paper reports on a 16-month-old boy with Fanconi's syndrome, in whom the slit-lamp examination did not show crystal deposits of cystine in the conjunctiva. The ultrastructural study of the conjunctival biopsy demonstrated polygonal crystals within double membrane-limited organelles located in fibroblasts. Similar crystals were subsequently found in a kidney biopsy. We therefore think that conjunctival biopsy is a valuable diagnostic tool prior to performing renal biopsy, even in cases with negative findings by ophthalmologic examination.

Immunohistological signposts in central nervous system tumours with neuronal differentiation.

25 neuronal tumours with a panel of antibodies were studied and it was found that vimentin was present in 15 tumours. It was also found in a few cells within rosettes. PGP 9.5 showed a somatic pattern of staining with nuclear and perinuclear positivity in 23. Neurofilament reactivity was found in 14. Retinal S-antigen was detected only in one medulloblastoma, 3/4 pineal tumours and 2/2 retinoblastomas. Reactivity, for synaptophysin was present in 2/5 medulloblastomas, 3/10 neuroblastomas and 2/2 retinoblastomas. GFAP was demonstrated in scattered tumour cells in 4/5 medulloblastomas. Two of these were the only tumours featuring bipolar differentiation whilst it was unipolar in the remainder. The significance of these findings in relation to the ontogeny of these tumours is discussed.

Haemangioblastoma: histological and immunohistological study of an enigmatic cerebellar tumour.

Paraffin-embedded blocks of 36 cerebellar haemangioblastomas were reacted with a panel of antibodies including glial fibrillary acidic protein, vimentin, epithelial membrane antigen, cytokeratin, Factor VIII, a neuroendocrine marker and with Ulex europaeus. agglutinin The main histological features, apart from the characteristic large abnormal vessels, were a prominent reticulin network, a cystic architecture and cellular and nuclear polymorphism. Two cell types were identified: endothelial and stromal. Twenty tumours were positive for glial fibrillary acidic protein because of included or reactive astrocytes as well as positive stromal cells. Vimentin was positive in all tumours with a diffuse distribution and a somatic pattern; blood vessels, stromal cells and reactive astrocytes were strongly positive. Factor VIII and Ulex europaeus agglutinin reactivity were present in a similar pattern of staining in endothelium and in five cases there were stromal cells that were positive with the latter. We were not able to ascertain the histogenesis of the stromal cell, which remains enigmatic.

Epithelial differentiation in gliomas, meningiomas and choroid plexus papillomas.

The immunohistological findings using antibodies to different intermediate filaments (glial fibrillary acidic protein, vimentin and two types of cytokeratin) and epithelial membrane antigen are described in 89 gliomas, 19 meningiomas and 8 choroid plexus papillomas (CPPs) from adult patients. All the patients had total or subtotal surgical excision of their tumours with clinical follow up for between 3 and 7 years. The immunohistological results were correlated with the histological features and patient survival. Tumours other than low grade astrocytomas, oligodendrogliomas and anaplastic ependymomas expressed one or more epithelial markers. This immunohistological evidence of epithelial differentiation in the absence of histological epithelial features in gliomas confirms that the two are not necessarily correlated. It is concluded that the expression of epithelial markers in some intradural tumours may reflect aberrant differentiation related to the degree of anaplasia in poorly differentiated astrocytomas and glioblastomas. All the patients with anaplastic epithelial marker-positive gliomas died within 1 year, whereas only 68% of patients with marker-negative tumours died within the follow-up period. In ependymomas and meningiomas, the expression of epithelial markers may reflect their histogenesis, while in malignant CPPs such expression could denote either their aberrant differentiation or histogenetic derivation.

La técnica de Mowry en el endometrio proliferativo de la paciente esteril / Mowry technic in the proliferative endometrium of the sterile patient

La biopsia del endometrio en la paciente estéril necesita de nuevos aportes para una mejor interpretación de los hallazgos clínicos y morfológicos. Esta investigación se ocupa de la aplicación de la técnica de Mowry para determinar prototipos histoquímicos en los endometrios proliferativos de las pacientes que consultaron por esterilidad. Se estudiaron retrospectivamente 52 biopsias provenientes de igual número de pacientes atendidas en distintos consultorios de ginecología de la fertilidad; se usaron como testigos, 47 endometrios provenientes de histerectomías simples. Se encontraron 4 prototipos de comportamiento estromal: Prototipo I (negatio total) o del endometrio del post aborto; el prototipo II (difuso y perivascular leve) del proliferativo ciclico temprano; el prototipo III (positivo difuso y perivascular intenso) del proliferativo ciclico medio y del monofásico y el prototipo IV (positivo focal leve o moderado) del proliferativo ciclico tardío. Se concluye que la técnica de Mowry aplicada a los endometrios proliferativos ciclicos y no ciclicos es un recurso complementario aplicable al material biópsico de la paciente que consulta por esterilidad