Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma.

BACKGROUND: Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively. METHODS: Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test. RESULTS: Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy. CONCLUSION: In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.

Treating advanced cancer of the gastro-oesophageal junction (GOJ) poses a challenge given its location in the distal oesophagus and proximal stomach, and whether it should be treated as oesophageal or gastric cancer. Given the indistinct location, it is unclear whether GOJ cancer should be treated with neoadjuvant chemoradiation, which is the treatment of choice for advanced oesophageal cancers, or perioperative chemotherapy, which is the treatment of choice for advanced gastric cancers. Few studies have addressed treatment options specifically for GOJ cancers. This study investigated whether there was a difference in survival between patients with GOJ cancer who were treated with chemoradiation versus chemotherapy.

National guidelines may reduce socioeconomic disparities in treatment selection for esophageal cancer.

The 2011 National Comprehensive Cancer Network guidelines first incorporated the results of the landmark CROSS trial, establishing induction therapy (chemotherapy ± radiation) and surgery as the treatment standard for locoregional esophageal cancer in the United States. The effect of guideline publication on socioeconomic status (SES) inequalities in cancer treatment selection remains unknown. Patients diagnosed with Stage II/III esophageal cancer between 2004 and 2013 who underwent curative treatment with definitive chemoradiation or multimodality treatment (induction and surgery) were identified from the Surveillance, Epidemiology and End Results (SEER)-Medicare registry. Clinicopathologic characteristics were compared between the two therapies. Multivariable regression analysis was used to adjust for known factors associated with treatment selection. An interaction term with respect to guideline publication and SES was included Of the 2,148 patients included, 1,478 (68.8%) received definitive chemoradiation and 670 (31.2%) induction and surgery. Guideline publication was associated with a 16.1% increase in patients receiving induction and surgery in the low SES group (21.4% preguideline publication vs. 37.5% after). In comparison, a 4.5% increase occurred during the same period in the high SES status group (31.8% vs. 36.3%). After adjusting for factors associated with treatment selection, guideline publication was associated with a 78% increase in likelihood of receiving induction and surgery among lower SES patients (odds ratio 1.78; 95% confidence interval (CI): 1.05,3.03). Following the new guideline publication, patients living in low SES areas were more likely to receive optimal treatment. Increased dissemination of guidelines may lead to increased adherence to evidence-based treatment standards.

Incidental ganglioneuromas: a presentation of 14 surgical cases and literature review.

BACKGROUND AND AIMS: Ganglioneuromas are benign tumors which originate from the neural crest. This tumor affects mainly young patients rather than adult ones, and its most frequent localizations are mediastinum, retroperitoneum, adrenal glands and cervical region. Usually, ganglioneuromas are discovered as incidentalomas since they are often asymptomatic, even if they could present sympathetic or mass-related symptoms. To obtain a definitive diagnosis, histological exam is necessary since CT scan and MRI are not capable of distinguishing ganglioneuromas from other tumors, such as neuroblastomas or pheocromocytomas. The surgical excision is the chosen treatment and it offers an excellent prognosis. METHODS: We conducted a retrospective analysis of our cases of ganglioneuroma from 2004 to 2014; this study aims to compare our experience with literature review (2000-2014). Data about patients' features, tumor localization, symptoms, treatment and follow-up were analyzed and reported in detailed tables. RESULTS: Between 2004 and 2014 we treated 14 patients affected by ganglioneuroma. For all of them the diagnosis was incidental; 9 out of 12 (64.3 %) patients presented an adrenal mass; in 2 patients (14.3 %) the tumor was localized in cervical region; in other 2 patients (14.3 %) the tumor was in the retroperitoneum and one patient (7.1 %) presented a ganglioneuroma in the costo-vertebral space. All our patients underwent surgical removal and none of them present surgery-related complications or recurrences to date. CONCLUSIONS: Our data widen the knowledge about ganglioneuroma and confirm that the surgical approach has an excellent prognosis with very low incidence of surgery-related complications and recurrences.

Anomalous Debye-like dielectric relaxation of water in micro-sized confined polymeric systems.

While it is well known that spatial confinement on a nm scale affects the molecular dynamics of water resulting in a hindered dipolar reorientation, question of whether these effects could result at length scales larger than these, i.e., in confined regions of the order of µm or more, is still under debate. Here we use dielectric relaxation spectroscopy techniques to study the relaxation orientation dynamics of water entrapped in different polymeric matrices with pore sizes of the order of 100 µm, analyzing the frequency relaxation behaviour of the dielectric response. Our results show that, contrary to what has been generally thought, even in confinements which are not particularly high such as those realized here, regions typically hundred micrometers in size can affect the water structure, inducing a water phase with properties different from those of bulk water. In particular, we observe a dielectric dispersion centered in the range 10(5)-10(7) Hz, in between the one characteristic of ice (8.3 kHz at T = 0 °C) and the one of bulk water (19.2 GHz at T = 25 °C). The analysis of the dependence on temperature of the relaxation time of this unexpected contribution rules out the possibility that it can be attributed to an interfacial polarization (Maxwell-Wagner effect) and suggests a dipolar Debye-like origin due to a slow-down of the hydrogen-bonded network orientational polarization. Also at these scales, the confinement alters the structure of water, leading to a hindered reorientation. These properties imply that water confined within these polymeric porous matrices is more ordered than bulk water. These findings may be important in order to understand biological processes in cells and in different biological compartments, where water is physiologically confined.

Human hepatoma cell lines on gas foaming templated alginate scaffolds for in vitro drug-drug interaction and metabolism studies.

Liver in vitro systems that allow reliable prediction of major human in vivo metabolic pathways have a significant impact in drug screening and drug metabolism research. In the present study, a novel porous scaffold composed of alginate was prepared by employing a gas-in-liquid foaming approach. Galactose residues were introduced on scaffold surfaces to promote cell adhesion and to enhance liver specific functions of the entrapped HepG2/C3A cells. Hepatoma cells in the gal-alginate scaffold showed higher levels of liver specific products (albumin and urea) and were more responsive to specific inducers (e.g. dexamethasone) and inhibitors (e.g. ketoconazole) of the CYP3A4 system than in conventional monolayer culture. HepG2/C3A cells were also more efficient in terms of rapid elimination of testosterone, used as a model substance, at rates comparable to those of in vivo excretion. In addition, an improvement in metabolism of testosterone, in terms of phase II metabolite formation, was also observed when the more differentiated HepaRG cells were used. Together the data suggest that hepatocyte/gas templated alginate-systems provide an innovative high throughput platform for in vitro drug metabolism and drug-drug interaction studies, with broad fields of application, and might provide a valid tool for minimizing animal use in preclinical testing of human relevance.

Dielectric characterization of hepatocytes in suspension and embedded into two different polymeric scaffolds.

The dielectric and conductometric properties of hepatocytes in two different environments (in aqueous suspension and embedded into polymeric scaffolds) have been investigated in the frequency range from 1 kHz to 2 GHz, where the interfacial electrical polarization gives rise to marked dielectric relaxation effects. We analyzed the dielectric behavior of hepatocytes in complete medium aqueous suspensions in the light of effective medium approximation for heterogeneous systems and hepatocytes cultured into two different highly porous and interconnected polymeric structures. In the former case, we have evaluated the passive electrical parameters associated with both the plasmatic and nuclear membrane, finding a general agreement with the values reported elsewhere, based on a partially different analysis of the experimental spectra. In the latter case, we have evaluated the cell growth into two different polymeric scaffolds made of alginate and gelatin with a similar pore distribution and similar inter-connectivity. Based on a qualitative analysis of the dielectric spectra, we were able to provide evidence that alginate scaffolds allow an overall survival of cells better than gelatin scaffold can do. These indications, confirmed by biological tests on cell viability, suggest that hepatocytes embedded in alginate scaffolds are able to perform liver specific functions even over on extended period of time.

A biomimetic porous hydrogel of gelatin and glycosaminoglycans cross-linked with transglutaminase and its application in the culture of hepatocytes.

The development of blended gelatin and glycosaminoglycan (GAG) scaffolds can potentially be used in many soft tissue engineering applications since these scaffolds mimic the structure and biological function of native extracellular matrix (ECM). In this study, we were able to obtain a gelatin-GAG scaffold by using a concentrated emulsion templating technique known as high internal phase emulsion (HIPE), in which a prevailing in volume organic phase is dispersed in the form of discrete droplets inside an aqueous solution of three biopolymers represented by gelatin, hyaluronic acid (HA) and chondroitin sulfate (CS) in the presence of a suitable surfactant. In order to preserve the bioactive potential of the biopolymers employed, the cross-linking procedure involved the use of transglutaminase (MTGase) that catalyzes the formation of covalent N-ε-(γ-glutamyl) lysine amide bonds. Since neither HA nor CS possess the necessary primary amino groups toward which MTGase is active, they were functionalized with the dipeptide glycine-lysine (GK). In this way the introduction of foreign cross-linking bridging units with an unpredictable biocompatibility was avoided. These enzymatic cross-linked gelatin-GAG scaffolds were tested in the culture of primary rat and C3A hepatocytes. Results underlined the good performance of this novel support in maintaining and promoting hepatocyte functions in vitro.