Micro-implant d'acétonide de fluocinolone (ILUVIEN(®)) pour l'oedème maculaire diabétique chronique [Fluocinolone acetonide (ILUVIEN®) micro-implant for chronic diabetic macular edema].

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy and may cause severe visual loss. In this article, we examine the pathophysiology of DME and review various treatment options, such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF) receptor antibodies, and steroids including ILUVIEN(®), which is a new sustained-release, non biodegradable, injectable, intravitreal micro-implant containing fluocinolone acetonide. The results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies, conducted to evaluate the efficacy and safety of ILUVIEN(®) in DME, are discussed

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery

Background: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. Patients and methods: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. Results: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. Conclusion: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcom

Influence of age on retinochoroidal healing processes after argon photocoagulation in C57bl/6j mice

PURPOSE: To analyze the influence of age on retinochoroidal wound healing processes and on glial growth factor and cytokine mRNA expression profiles observed after argon laser photocoagulation. METHODS: A cellular and morphometric study was performed that used 44 C57Bl/6J mice: 4-week-old mice (group I, n=8), 6-week-old mice (group II, n=8), 10-12-week-old mice (group III, n=14), and 1-year-old mice (group IV, n=14). All mice in these groups underwent a standard argon laser photocoagulation (50 microm, 400 mW, 0.05 s). Two separated lesions were created in each retina using a slit lamp delivery system. At 1, 3, 7, 14, 60 days, and 4 months after photocoagulation, mice from each of the four groups were sacrificed by carbon dioxide inhalation. Groups III and IV were also studied at 6, 7, and 8 months after photocoagulation. At each time point the enucleated eyes were either mounted in Tissue Tek (OCT), snap frozen and processed for immunohistochemistry or either flat mounted (left eyes of groups III and IV). To determine, by RT-PCR, the time course of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and monocyte chemotactic protein-1 (MCP-1) gene expression, we delivered ten laser burns (50 microm, 400 mW, 0.05 s) to each retina in 10-12-week-old mice (group III', n=10) and 1-year-old mice (group IV', n=10). Animals from Groups III' and IV' had the same age than those from Groups III and IV, but they received ten laser impacts in each eye and served for the molecular analysis. Mice from Groups III and IV received only two laser impacts per eye and served for the cellular and morphologic study. Retinal and choroidal tissues from these treated mice were collected at 16 h, and 1, 2, 3, and 7 days after photocoagulation. Two mice of each group did not receive photocoagulation and were used as controls. RESULTS: In the cellular and morphologic study, the resultant retinal pigment epithelium interruption expanse was significantly different between the four groups. It was more concise and smaller in the oldest group IV (112.1 microm+/-11.4 versus 219.1 microm+/-12.2 in group III) p<0.0001 between groups III and IV. By contrast, while choroidal neovascularization (CNV) was mild and not readily identifiable in group I, at all time points studied, CNV was more prominent in the (1-year-old mice) Group IV than in the other groups. For instance, up to 14 days after photocoagulation, CNV reaction was statistically larger in group IV than in group III ((p=0.0049 between groups III and IV on slide sections and p<0.0001 between the same groups on flat mounts). Moreover, four months after photocoagulation, the CNV area (on slide sections) was 1,282 microm(2)+/-90 for group III and 2,999 microm(2)+/-115 for group IV (p<0.0001 between groups III and IV). Accordingly, GFAP, VEGF, and MCP-1 mRNA expression profiles, determined by RT-PCR at 16 h, 1, 2, 3, and 7 days postphotocoagulation, were modified with aging. In 1-year-old mice (group IV), GFAP mRNA expression was already significantly higher than in the younger (10-12 week) group III before photocoagulation. After laser burns, GFAP mRNA expression peaked at 16-24 h and on day 7, decreasing thereafter. VEGF mRNA expression was markedly increased after photocoagulation in old mice eyes, reaching 2.7 times its basal level at day 3, while it was only slightly increased in young mice (1.3 times its level in untreated young mice 3 days postphotocoagulation). At all time points after photocoagulation, MCP-1 mRNA expression was elevated in old mice, reaching high levels of expression at 16 h and day 3 respectively. CONCLUSIONS: Our results were based on the study of four different age groups and included not only data from morphological observations but also from a molecular analysis of the various alterations of cytokine signaling and expression. One-year-old mice demonstrated more extensive CNV formation and a slower pace of regression after laser photocoagulation than younger mice. These were accompanied by differences in growth factors and cytokine expression profiles indicate that aging is a factor that aggravates CNV. The above results may provide some insight into possible therapeutic strategies in the future

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer

Background: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. Patients and methods: A large series of surgically resected liver metastases (n = 153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (α-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. Results: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. Conclusions: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplati

Defining Long-Term Survivors Following Resection of Intrahepatic Cholangiocarcinoma

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. METHODS: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5). RESULTS: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived  5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT. CONCLUSION: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.info:eu-repo/semantics/publishedVersio

Long-Term Outcomes After Curative Resection of HCV-Positive Versus Non-Hepatitis Related Hepatocellular Carcinoma: an International Multi-Institutional Analysis

Background: To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades. Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias. Results: Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000-2009 55% vs. 2010-2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000-2009 53% vs. 2010-2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients. Conclusion: While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable.info:eu-repo/semantics/publishedVersio

Proposed Modification of the Eighth Edition of the AJCC Staging System for Intrahepatic Cholangiocarcinoma

Background: To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. Methods: Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (≥3 LNM). Results: The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p < 0.05), and SEER (Median OS, stage I 87.0 vs. II 29.3 vs. III 17.7 vs. IV 14.2 months, all p < 0.05) datasets, which was also verified among patients who had ≥6 lymph node harvested from both databases. Conclusion: The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.info:eu-repo/semantics/publishedVersio

Impact of Microvascular Invasion on Clinical Outcomes After Curative-Intent Resection for Intrahepatic Cholangiocarcinoma

Background: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC. Methods: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI). Results: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P 18 months) prognosis. Conclusions: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.info:eu-repo/semantics/publishedVersio