Accelerated Corneal Collagen Cross-Linking Using Topography-Guided UV-A Energy Emission: Preliminary Clinical and Morphological Outcomes

Purpose. To assess the clinical and morphological outcomes of topography-guided accelerated corneal cross-linking. Design. Retrospective case series. Methods. 21 eyes of 20 patients with progressive keratoconus were enrolled. All patients underwent accelerated cross-linking using an ultraviolet-A (UVA) exposure with an energy release varying from 7.2 J/cm2 up to 15 J/cm2, according to the topographic corneal curvature. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, topography, in vivo confocal microscopy (IVCM), and anterior segment optic coherence tomography (AS-OCT) were evaluated preoperatively and at the 1, 3, 6, and 12 months postoperatively. Results. 12 months after surgery UDVA and CDVA did not significantly vary from preoperative values. The average topographic astigmatism decreased from -4.61±0.74 diopters (D) to -3.20±0.81 D and coma aberration improved from 0.95 ± 0.03 μm to 0.88 ± 0.04 μm after surgery. AS-OCT and IVCM documented differential effects on the treated areas using different energies doses. The depths of demarcation line and keratocyte apoptosis were assessed. Conclusions. Preliminary results show correspondence between the energy dose applied and the microstructural stromal changes induced by the cross-linking at various depths in different areas of treated cornea. One year after surgery a significant reduction in the topographic astigmatism and comatic aberration was detected. None of the patients developed significant complications

Peritoneal carcinomatosis

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease. (C) 2013 Baishideng Publishing Group Co., Limited. All rights reserved

Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results

Complex retinal detachment in phakic patients: previtrectomy. Phacoemulsification Versus Combined Phacovitrectomy

PURPOSE:: To assess the impact of phacoemulsification performed one week before pars plana vitrectomy versus combined phacovitrectomy on postoperative anterior segment status and final functional and anatomical outcomes in phakic patients affected by complex rhegmatogenous retinal detachment. METHODS:: The authors retrospectively reviewed the records of 59 phakic patients affected by complex rhegmatogenous retinal detachment. Twenty-nine patients underwent cataract surgery 7 days before vitrectomy (preemptive cataract surgery—Group 1), whereas 30 patients underwent combined phacovitrectomy (Group 2). Preoperative, intraoperative, early- and late-postoperative outcomes were measured and compared. RESULTS:: Numbers of previous retinal surgical procedures, nuclear sclerosis grade, proliferative vitreoretinopathy grade, eyes with inferior breaks, surgical time, and ratio of silicone oil/gas tamponade were all similar between the two groups. After surgery, there was less extension of posterior synechia in Group 1. There was no significant difference in fibrin, number of patients with posterior synechia, final intraocular pressure, retinal redetachment rate, final retinal status, or final best-corrected visual acuity. CONCLUSION:: Preemptive cataract surgery was associated with less extensive postoperative posterior synechia, however, its final functional and anatomical outcomes were not significantly different from those of phacovitrectomy. Both approaches were efficacious.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially

Possible additional value of 18FDG-PET in managing pancreas intraductal papillary mucinous neoplasms: Preliminary results

Although some clinical and radiological features may predict malignancy presence in intraductal papillary mucinous pancreas neoplasms, preoperative diagnosis remains difficult. In this study we present 7 patients with Intraductal Papillary Mucinous Neoplasm (IPMN) studied both with 18FDG-PET and magnetic resonance cholangiopancreatography (MRCP). A focal hypermetabolism was documented in 2 patients (the standardized uptake value in the neoplastic foci was 6.7 and 9), while absence of FDG uptake in the neoplasm area was recorded in the remaining 5 cases. Mean follow-up was 27 months (range 21–34). The final judgement was benign IPMN in 5 cases and malignant IPMN in 2. PET scan always correctly predicted the presence or absence of malignancy, while MRCP failed to detect malignancy in 3/7 cases. In conclusion, this preliminary experience suggests that 18FDG-PET may prove useful for malignancy detection in IPMN, improving differential diagnosis with benign intraductal papillary growth by functional data

Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation

Background and Aims: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. Methods: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012–2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam- D'Agostino test was used to evaluate the calibration of the models. Results: GEMA-Na (concordance = .82, 95% CI = .75–. 89), MELD 3.0 (concordance = .81, 95% CI = .74–. 87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74–.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed

Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications

<p>Abstract</p> <p>Background</p> <p>Intraductal papillary mucinous neoplasms (IPMNs) are increasingly recognized entities, whose management remains sometimes controversial, due to the high rate of benign lesions and on the other side to the good survival after resection of malignant ones.</p> <p>Methods</p> <p>Retrospective analysis of a prospectively collected Western series of IPMN.</p> <p>Results</p> <p>Forty cases of IPMN were analysed (1992-2007). Most patients were symptomatic (72.5%); cholangio-MRI had the best diagnostic accuracy both for the tumour nature (83.3%) and for the presence of malignancy (57.1%). ERCP was done in 8 cases (20%), and the results were poor. Thirteen patients were treated by pancreatic resection and 27 were maintained in follow-up. Total pancreatectomy was performed in 46% of the cases; in situ and invasive carcinoma were recognized in 15.4% and 38.4% of the cases, respectively. The mean follow-up was 42 months (range 12-72). One only patients with nodal metastases died 16 months after the operation for disease progression, while 91.6% of the operated patients are disease free. Out of the 27 not resected patients, 2 out of 4 presenting a lesion at high risk for malignancy died, while the remaining are in good conditions and disease free, with a mean follow-up of 31 months.</p> <p>Conclusion</p> <p>Therapeutic indication for IPMNs is mainly based upon radiological evaluation of the risk of malignancy. While the main duct tumours should be resected, preserving whenever possible a portion of the gland, the secondary ducts tumours may be maintained under observation, in absence of radiological elements of suspicion such as size larger than 3 cm, or a wall greater than 3 mm or nodules or papillae in the context of the cyst.</p

HTRA1 and TGF-β1 concentrations in the aqueous humor of patients with neovascular age-related macular degeneration

PURPOSE: To evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), transforming growth factor beta 1 (TGF-β1), bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and vascular endothelial growth factor A (VEGFA) proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to age-related macular degeneration. METHODS: We measured by ELISA the concentrations of HTRA1, TGF-β1, BMP4, GDF6 and VEGFA in the aqueous humor of 23 patients affected by nCNV who received 3 consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). 23 age-matched cataract patients served as controls. RESULTS: BMP4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P<0.0001), and higher than both the month 1 (P<0.0001) and the month 2 (P<0.0001) values. Baseline VEGFA was higher than controls (P<0.0001), not different from month 1 value (P=0.0821), but higher than month 2 value (P<0.0001). Baseline TGF-β1 was higher than controls (P=0.0015) and not different from month 1 (P=0.129) and month 2 values (P=0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-β1, HTRA 1 and VEGFA, or TGF-β1 and VEGFA. CONCLUSIONS: In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in nAMD and a VEGFA-independent role for TGF-β1

Optimized EGFR blockade strategies in <i>EGFR</i> addicted gastroesophageal adenocarcinomas

Purpose: Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.Experimental Design: We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX).Results: The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that EGFR amplification drives aggressive behavior and poor prognosis. We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. In a highly EGFR-amplified nonresponding PDX, where resistance to EGFR drugs was due to inactivation of the TSC2 tumor suppressor, cotreatment with the mTOR inhibitor everolimus restored sensitivity to EGFR inhibition.Conclusions: This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors