Pathological and Molecular Diagnosis of Uveal Melanoma.

(1) Background: Uveal melanoma (UM) is a common malignant intraocular tumor that presents with significant genetic differences to cutaneous melanoma and has a high genetic burden in terms of prognosis. (2) Methods: A systematic literature search of several repositories on uveal melanoma diagnosis, prognosis, molecular analysis, and treatment was conducted. (3) Results: Recent genetic understanding of oncogene-initiation mutations in GNAQ, GNA11, PLCB4, and CYSLTR2 and secondary progression drivers of BAP1 inactivation and SF3B1 and EIF1AX mutations offers an appealing explanation to the high prognostic impact of adding genetic profiling to clinical UM classification. Genetic information could help better explain peculiarities in uveal melanoma, such as the low long-term survival despite effective primary tumor treatment, the overwhelming propensity to metastasize to the liver, and possibly therapeutic behaviors. (4) Conclusions: Understanding of uveal melanoma has improved step-by-step from histopathology to clinical classification to more recent genetic understanding of oncogenic initiation and progression.

Characterization of the Tongue Worm, Linguatula serrata (Pentastomida), Identified from Hares (Lepus europaeus) in Romania.

Linguatula serrata (Frölich, 1789) is a widespread parasite known as the tongue worm belonging to the family Linguatulidae. The adult form of the parasite is usually located in the upper respiratory tract of domestic and wild carnivores while the larval forms are located in the visceral organs of intermediate hosts (various herbivorous mammals). Twenty-four European brown hares (Lepus europaeus) were examined in this study, of which two were positive with L. serrata nymphs. The collected nymphs were examined morphologically using electron-microscopic analysis and molecularly by amplification of 18S rRNA and COX1 genes. Lung tissue samples were also collected and histopathological examination was performed. Histopathological examination revealed the following lesions: generalized inflammatory oedema, granulomas with necrosis, calcification and fibrosis in the bronchial tree. The results of molecular sequencing for L. serrata specimens collected from the European brown hares are deposited in GenBank. This study presents the first report on Linguatula serrata nymphs collected from L. europaeus in Romania, using molecular and morphological characterization simultaneously.

The Effects of Oncological Treatment on Redox Balance in Patients with Uveal Melanoma.

(1) Background: Uveal malignant melanoma is the most common adult eye cancer and presents metabolic reprogramming that affects the tumoral microenvironment by altering the redox balance and producing oncometabolites. (2) Methods: The study prospectively evaluated patients undergoing enucleation surgery or stereotactic radiotherapy for uveal melanoma by following systemic oxidative-stress redox markers serum lipid peroxides, total albumin groups and total antioxidant levels (3) Results: Serum antioxidants and lipid peroxides were elevated from pre-treatment to longer-term follow-up. Antioxidants inversely correlated to lipid peroxides: higher in stereotactic radiosurgery patients pre/6/12/18 months post-treatment (p = 0.001-0.049) versus higher lipid peroxides in enucleation surgery patients pre/after/6 months post-treatment (p = 0.004-0.010). An increased variance in serum antioxidants was observed for enucleation surgery patients (p < 0.001), however enucleation did not increase mean serum antioxidants or albumin thiols; only lipid peroxides were increased post-enucleation (p < 0.001) and at 6-month follow-up (p = 0.029). Mean albumin thiols were increased for 18- and 24-month follow-ups (p = 0.017-0.022). Males who had enucleation surgery presented higher variance in serum determinations and overall higher lipid peroxides values pre/post-treatment and at the 18-month follow-up. (4) Conclusions: Initial oxidative stress-inducing events of surgical enucleation or stereotactic radiotherapy for uveal melanoma are followed by a longer-term inflammatory cascade gradually subsiding at later follow-ups.

Burn mass casualty incidents in Europe: A European response plan within the European Union Civil Protection Mechanism.

BACKGROUND: Burn care is centralized in highly specialized burn centers in Europe. These centers are of limited capacity and may be overwhelmed by a sudden surge in case of a burn mass casualty incident. Prior incidents in Europe and abroad have sustained high standards of care through well-orchestrated responses to share the burden of care in several burn centers. A burn mass casualty incident in Romania in 2015 sparked an initiative to strengthen the existing EU mechanisms. This paper aims to provide insight into developing a response plan for burn mass casualties within the EU Civil Protection Mechanism. METHODS: The European Burns Association drafted medical guidelines for burn mass casualty incidents based on a literature review and an in-depth analysis of the Romanian incident. An online questionnaire surveyed European burn centers and EU States for burn mass casualty preparedness. RESULTS: The Romanian burn mass casualty in 2015 highlighted the lack of a burn-specific mechanism, leading to the late onset of international transfers. In Europe, 71% of respondents had existing mass casualty response plans, though only 35% reported having a burn-specific plan. A burns response plan for burn mass casualties was developed and adopted as a Commission staff working document in preparation for further implementation. The plan builds on the existing Union Civil Protection Mechanism framework and the standards of the WHO Emergency Medical Teams initiative to provide 1) burn assessment teams for specialized in-hospital triage of patients, 2) specialized burn care across European burn centers, and 3) medevac capacities from participating states. CONCLUSION: The European burn mass casualty response plan could enable the delivery of high-level burn care in the face of an overwhelming incident in an affected European country. Further steps for integration and implementation of the plan within the Union Civil Protection Mechanism framework are needed.

Underlying Ciliary Body Uveal Melanoma in a Patient with Chronic Lymphocytic Leukemia Presenting for Hyphema.

(1) Background: Ciliary body uveal melanoma is a rare subtype of uveal melanoma which comprises 3-5% of melanomas, an immunogenic cancer, and can present multifaceted initial clinical manifestations, masquerading as various ocular pathologies. Chronic lymphocytic leukemia (CLL) presents immunodeficiency and risk for the development of a secondary malignancy, with Bruton's tyrosine kinase inhibitor treatment having a mutagenic effect and a secondary anti-platelet aggregation effect. We present the case of a 65-year-old patient undergoing treatment for CLL with ibrutinib who presented with recurrent hyphema that masked an underlying, inferiorly situated, ciliary body uveal melanoma; (2) Methods: Retrospective case review; (3) Results: An ophthalmological examination together with imaging via mode B ultrasound and contrast-enhanced magnetic resonance imaging resulted in the clinical and imagistic diagnosis of a ciliary body uveal melanoma. A pathological examination of the enucleated eye confirmed the diagnosis. Postoperative tumoral reoccurrence was not detected for 1½ years, however, CLL immunosuppression worsened with admission for severe COVID-19 disease. (4) Conclusions: CLL patient screening for melanoma should also include detailed ophthalmological examinations, which could also include ultrasound ophthalmological imaging. The avoidance of uveal melanoma metastatic disease is paramount for patient survival. CLL manifests additional profound immunosuppression.

A simplified fluid resuscitation formula for burns in mass casualty scenarios: Analysis of the consensus recommendation from the WHO Emergency Medical Teams Technical Working Group on Burns.

BACKGROUND: Burn fluid resuscitation guidelines have not specifically addressed mass casualty with resource limited situations, except for oral rehydration for burns below 40% total body surface area (TBSA). The World Health Organization Technical Working Group on Burns (TWGB) recommends an initial fluid rate of 100 mL/kg/24 h, either orally or intravenously, beyond 20% TBSA burned. We aimed to compare this formula with current guidelines. METHODS: The TWGB formula was numerically compared with 2-4 mL/kg/%TBSA for adults and the Galveston formula for children. RESULTS: In adults, the TWGB formula estimated fluid volumes within the range of current guidelines for burns between 25 and 50% TBSA, and a maximal 20 mL/kg/24 h difference in the 20-25% and the 50-60% TBSA ranges. In children, estimated resuscitation volumes between 20 and 60% TBSA approximated estimations by the Galveston formula, but only partially compensated for maintenance fluids. Beyond 60% TBSA, the TWGB formula underestimated fluid to be given in all age groups. CONCLUSION: The TWGB formula for mass burn casualties may enable appropriate fluid resuscitation for most salvageable burned patients in disasters. This simple formula is easy to implement. It should simplify patient management including transfers, reduce the risk of early complications, and thereby optimize disaster response, provided that tailored resuscitation is given whenever specialized care becomes available.

Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study.

BACKGROUND: Erlotinib, docetaxel, and pemetrexed are approved for the second-line treatment of non-small-cell lung cancer (NSCLC), but no head-to-head data from large clinical trials are available. We undertook the Tarceva In Treatment of Advanced NSCLC (TITAN) study to assess the efficacy and tolerability of second-line erlotinib versus chemotherapy in patients with refractory NSCLC. METHODS: TITAN was an international, randomised multicentre, open-label, phase 3 study that was done at 77 sites in 24 countries. Chemotherapy-naive patients with locally advanced, recurrent, or metastatic NSCLC received up to four cycles of first-line platinum doublet chemotherapy, after which patients with disease progression during or immediately after chemotherapy were offered enrolment into TITAN. Enrolled patients were randomly assigned (1:1) by a minimisation method to ensure balanced stratification, to receive erlotinib 150 mg/day or chemotherapy (standard docetaxel or pemetrexed regimens, at the treating investigators' discretion), until unacceptable toxicity, disease progression, or death. Patients were stratified by disease stage, Eastern Cooperative Oncology Group performance status, smoking history, and region of residence. The primary endpoint was overall survival in the intention-to-treat population. TITAN was halted prematurely because of slow recruitment. This study is registered with ClinicalTrials.gov, number NCT00556322. FINDINGS: Between April 10, 2006, and Feb 24, 2010, 2590 chemotherapy-naive patients were treated with first-line platinum doublet chemotherapy, of whom 424 had disease progression and were enrolled into TITAN. 203 patients were randomly assigned to receive erlotinib and 221 were assigned to receive chemotherapy. Median follow-up was 27·9 months (IQR 11·0-36·0) in the erlotinib group and 24·8 months (12·1-41·6) in the chemotherapy group. Median overall survival was 5·3 months (95% CI 4·0-6·0) with erlotinib and 5·5 months (4·4-7·1) with chemotherapy (hazard ratio [HR] 0·96, 95% CI 0·78-1·19; log-rank p=0·73). The adverse-event profile of each group was in line with previous studies. Rash (98/196 [50%] in the erlotinib group vs 10/213 [5%] in the chemotherapy group for all grades; nine [5%] vs none for grade 3 or 4) and diarrhoea (36 [18%] vs four [2%] for all grades; five [3%] vs none for grade 3 or 4) were the most common treatment-related adverse events with erlotinib, whereas alopecia (none vs 23 [11%] for all grades; none vs one [<1%] for grade 3/4) was the most common treatment-related adverse event with chemotherapy. INTERPRETATION: No significant differences in efficacy were noted between patients treated with erlotinib and those treated with docetaxel or pemetrexed. Since the toxicity profiles of erlotinib and chemotherapy differ, second-line treatment decisions should take into account patient preference and specific toxicity risk profiles. FUNDING: F Hoffmann-La Roche.

Gastrointestinal robot-assisted surgery. A current perspective.

Minimally invasive techniques have revolutionized operative surgery. Computer aided surgery and robotic surgical systems strive to improve further on currently available minimally invasive surgery and open new horizons. Only several centers are currently using surgical robots and publishing data. In gastrointestinal surgery, robotic surgery is applied to a wide range of procedures, but is still in its infancy. Cholecystectomy, Nissen fundoplication and Heller myotomy are among the most frequently performed operations. The ZEUS (Computer Motion, Goleta, CA) and the da Vinci (Intuitive Surgical, Mountain View, CA) surgical systems are today the most advanced robotic systems used in gastrointestinal surgery. Most studies reported that robotic gastrointestinal surgery is feasible and safe, provides improved dexterity, better visualization, reduced fatigue and high levels of precision when compared to conventional laparoscopic surgery. Its main drawbacks are the absence of force feedback and extremely high costs. At this moment there are no reports to clearly demonstrate the superiority of robotics over conventional laparoscopic surgery. Further research and more prospective randomized trials are needed to better define the optimal application of this new technology in gastrointestinal surgery.