Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report.

A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Reversion from basal histone H4 hypoacetylation at the replication fork increases DNA damage in FANCA deficient cells.

The FA/BRCA pathway safeguards DNA replication by repairing interstrand crosslinks (ICL) and maintaining replication fork stability. Chromatin structure, which is in part regulated by histones posttranslational modifications (PTMs), has a role in maintaining genomic integrity through stabilization of the DNA replication fork and promotion of DNA repair. An appropriate balance of PTMs, especially acetylation of histones H4 in nascent chromatin, is required to preserve a stable DNA replication fork. To evaluate the acetylation status of histone H4 at the replication fork of FANCA deficient cells, we compared histone acetylation status at the DNA replication fork of isogenic FANCA deficient and FANCA proficient cell lines by using accelerated native immunoprecipitation of nascent DNA (aniPOND) and in situ protein interactions in the replication fork (SIRF) assays. We found basal hypoacetylation of multiple residues of histone H4 in FA replication forks, together with increased levels of Histone Deacetylase 1 (HDAC1). Interestingly, high-dose short-term treatment with mitomycin C (MMC) had no effect over H4 acetylation abundance at the replication fork. However, chemical inhibition of histone deacetylases (HDAC) with Suberoylanilide hydroxamic acid (SAHA) induced acetylation of the FANCA deficient DNA replication forks to levels comparable to their isogenic control counterparts. This forced permanence of acetylation impacted FA cells homeostasis by inducing DNA damage and promoting G2 cell cycle arrest. Altogether, this caused reduced RAD51 foci formation and increased markers of replication stress, including phospho-RPA-S33. Hypoacetylation of the FANCA deficient replication fork, is part of the cellular phenotype, the perturbation of this feature by agents that prevent deacetylation, such as SAHA, have a deleterious effect over the delicate equilibrium they have reached to perdure despite a defective FA/BRCA pathway.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

PURPOSE: To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). METHOD AND MATERIALS: All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. RESULTS: ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. CONCLUSION: The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Pharmacokinetic/Pharmacodynamic Index Linked to In Vivo Efficacy of the Ampicillin-Ceftriaxone Combination against Enterococcus faecalis.

Combination therapy with ampicillin plus ceftriaxone (AMP+CRO) is the first-line therapy for treating severe infections due to Enterococcus faecalis. However, the pharmacokinetic/pharmacodynamic (PK/PD) index linked to the in vivo efficacy of the combination is not yet defined, hindering dose optimization in the clinic. Because classical PK/PD indices are not directly applicable to antimicrobial combinations, two novel indices were tested in the optimized murine model of infection by E. faecalis to delineate the potentiation of AMP by CRO: the time above the CRO threshold (T>threshold) and the time above the AMP instantaneous MIC (T>MICi). The potential clinical relevance was evaluated by simulating human doses of AMP and CRO. Hill's equation fitted well the exposure-response data in terms of T>threshold, with a CRO threshold of 1 mg/L. The required exposures were 46%, 49%, and 52% for stasis and 1- and 2-log10 killing, respectively. Human ceftriaxone doses of 2 g every 12 h (q12h) would reach the target in >90% of strains with thresholds ≤64 mg/L. The AMP T>MICi index also fitted well, and the required exposures were 37%, 41%, and 46% for stasis and 1- and 2-log10 killing, respectively. In humans, the addition of CRO would allow use of lower AMP doses to reach the same T>MICi and to treat strains with higher MICs. This is the first report of the PK/PD indices and required magnitudes linked to AMP+CRO against E. faecalis; these results can be used as the basis to guide the design of clinical trials to improve combined therapy against enterococci.

Postnatal Surgical Correction of Myelomeningoceles: Preoperative and Intraoperative Risk Factors Associated with Postoperative Neurologic Outcomes.

OBJECTIVE: Open spina bifida or myelomeningocele (MMC) is a congenital defect that results from failure of caudal neurulation. We present a case series of patients who were treated with postnatal surgical correction for MMC, evaluating the possible preoperative and intraoperative risk factors associated with neurologic outcomes. METHODS: A retrospective chart review of patients who underwent postnatal surgical correction for MMCs over 11 years at our institution was performed. MMCs were classified based on their morphologic configuration into 3 types. Type I includes defects without a sac and there is cerebrospinal fluid (CSF) leak. Type II includes where there is a sac ≤4 cm, with or without CSF leak. Type III includes defects with a sac that are greater than 4 cm. RESULTS: Fifty patients were included. The median age of gestation at surgery was 37.4 weeks. There were 30 females (60%). All mothers received adequate folate supplementation. All patients underwent surgical correction in the first 48 hours. Lower extremity motor function at the last clinical follow-up was normal in 34 patients (68%). CSF leak, infection, and mortality were 8%, 2%, and 0%, respectively. Twenty-one patients (42%) underwent ventriculoperitoneal shunt for hydrocephalus. CONCLUSIONS: Despite there being no statistically significant associations with a timely closure, all cases were treated within the first 48 hours and this could influence the low complication rate. Individuals of Hispanic background who received appropriate folate supplementation still had high rates of MMC and we posit that this may be caused in part by a genetic/molecular predisposition.

Carcinoma de células escamosas corneal em um cão - uso da Mitomicina C 0, 02% como adjuvante no tratamento / Corneal squamous cell carcinoma in a dog - use of Mitomycin C 0. 02% as an adjuvant therapy

Background: Although Squamous Cell Carcinoma (SCC) is most commonly seen in the epidermis, this malignant neoplasm can manifest in various other tissues. A wide range of factors may be related to the development of SCC in the cornea, with continuous exposure to ultraviolet radiation and chronic friction to the ocular surface being the most accepted theories. In addition to surgical procedures, the use of mitomycin C in the topical treatment of corneal SCC has shown good results in therapeutic management. Thus, the objective of the current work is to report the satisfactory response observed in the use of mitomycin C in a case of SCC in the cornea of a dog. Case: A 9-year-old male Pug dog was attended by the Veterinary Ophthalmology and Microsurgery Sector (SOMVET) of the University Veterinary Hospital (HVU) of the Federal University of Santa Maria (UFSM) with Squamous Cell Carcinoma (SCC) in the cornea of the left eye, which had recurred after a previous surgical intervention. Secretion and discomfort in the left eye were noted during clinical examination. In addition, both eyes presented pigmentary keratitis in the medial corner. Surgical excision of the neoplasm was performed using the surgical technique of anterior lamellar keratectomy. In the immediate postoperative period, topical therapy was started with eye drops based on mitomycin C at 0.02%, for a period of 28 consecutive days. The use of this chemotherapy drug in the topical form was intended to minimize the chances of recurrence of the clinical condition, since the patient is predisposed to this alteration. In addition, supportive therapy was implemented to improve patient comfort, consisting of the use of tobramycin-based eye drops (6 times a day, for 14 days), atropine 1% eye drops (BID, for 3 days), lubricating eye drops based on sodium hyaluronate (3 times a day, for continuous use), and immunomodulatory eye drops based on tacrolimus 0.02% (twice a day, for continuous use). The patient was evaluated 7, 14, 21, and 28 days after surgery, when good results were observed. One year after treatment, the dog was still showing no signs of recurrence of the treated clinical condition. Discussion: It is known that chronic friction on the surface of the cornea predisposes to the diagnosis of corneal SCC. Accordingly, in the clinical examination of the patient in this report, the presence of bilateral pigmentary keratitis was observed, an alteration that leads to a framework of chronic aggression to the cornea. Surgical treatment is recommended to remove the tumor mass in the ocular region. However, in cases of corneal SCC, the literature highlights that recurrence after surgical excision is a common factor. As the patient in this study arrived at the clinic with a history of recurrence, topical therapy with mitomycin C associated with surgical treatment was instituted. This chemotherapy drug has shown encouraging results in the treatment of some neoplasms, especially SCC. Its use in this case supported previous findings, pointing to a satisfactory result in which the patient had no recurrences after one year of follow-up. In addition, the concentration and frequency used of the active ingredient did not lead to adverse effects in the short or medium term.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

Subtenon triamcinolone as an adjuvant in mitomycin-C-enhanced trabeculectomy in non-inflammatory glaucomas: A randomized clinical trial.

This unicentric randomized clinical trial was designed to compare the surgical outcomes of mitomycin C-enhanced trabeculectomy (MMC-TRAB) with and without subtenon triamcinolone acetonide (TAAC) injection in patients with non-inflammatory glaucomas. This trial is registered at the Brazilian Registry of Clinical Trials (ReBEC) under the register number RBR-53f8nh. Consecutive non-inflammatory glaucoma patients requiring surgical intervention were randomized into two groups. In the control group, eyes underwent standard MMC-TRAB, while in the intervention group, besides the standard MMC-TRAB, these eyes also received a subtenon TAAC injection (4mg) close to the bleb site at the end of the surgery. The main outcomes of the study were surgical success rates, intraocular pressure (IOP) and number of medications at all timepoints. Success was defined as IOP ≤ 15 mmHg and subdivided in complete or qualified according to the need of medication. A total of 75 eyes of 63 different patients were included (intervention group = 39 eyes; control group = 36 eyes). There was no difference between groups at baseline (p>0.11). Multivariable regression analysis indicated that IOP levels were significantly lower in the intervention group at 18 and 24 months of follow-up when number of medications was considered as a covariate (P<0.001). Complete success rates were higher in the intervention group at 06 (90.9% vs 68.7%; p = 0.03), 12 (87.2% vs 66.7%; p = 0.02) and 18 months (87.2% vs 66.7%; p = 0.02). Additionally, although success rates at 24 months were higher in the intervention group (82.0% vs 66.7%; p = 0.09), this difference did not reach statistical significance. Qualified success rates did not significantly differ between groups at all timepoints. In conclusion, this study found significantly lower IOPs levels at 18 and 24 months of follow-up and higher complete success rates until 18 months of follow-up, with the use of subtenon TAAC as an adjuvant to standard MMC-TRABs in non-inflammatory glaucoma patients.

Síndrome de Axenfeld-Rieger con glaucoma asociado / Axenfeld-Rieger syndrome associated with glaucoma

El síndrome de Axenfeld-Rieger es una enfermedad congénita que puede estar asociada a glaucoma en el 50 por ciento de los casos. Por esta razón se describen un caso clínico con síndrome de Axenfeld-Rieger y glaucoma bilateral. Se trata de un paciente masculino de 18 años con escleras azules, microcórnea, embriotoxon posterior, aniridia parcial, atrofia sectorial del iris y alteraciones sistémicas asociado a glaucoma, al que se decide realizar trabéculo-trabeculectomía en ambos ojos. Al mes de la cirugía se constata un aumento de las presiones intraoculares del ojo izquierdo y se realiza trabéculo-trabeculectomía con mitomicina C, posteriormente se hace necesario implantar válvula de Ahmed con mitomicina C en dicho ojo e implantar dispositivo de molteno en ojo derecho, el cual necesitó revisión con aguja y administración de mitomicina C para mantener presiones intraoculares dentro de límites normales con tratamiento médico asociado en ojo izquierdo(AU)

Axenfeld-Rieger syndrome is a congenital disease that can be associated with glaucoma in 50 percent of cases. For this reason, a clinical case with Axenfeld-Rieger syndrome and bilateral glaucoma is described. This is an 18-year-old male patient with blue sclera, microcornea, posterior embryotoxon, partial aniridia, sectorial atrophy of the iris, and systemic alterations associated with glaucoma, who decided to perform trabeculo-trabeculectomy in both eyes. One month after surgery, an increase in intraocular pressures in the left eye was observed and a trabeculo-trabeculectomy was performed with mitomycin C, subsequently it was necessary to implant Ahmed's valve with mitomycin C in said eye and implant a molteno device in the right eye, the which required revision with a needle and administration of mitomycin C to maintain intraocular pressures within normal limits with associated medical treatment in the left eye(AU)

Resultados refractivos y visuales en cirugía fotoablativa en pacientes miopes / Refractive and visual results in photoablative surgery in myope patients

Objetivo: Evaluar los resultados refractivos y visuales post cirugía refractiva corneal con láser de excímero (LASEK-MMC o PRK-MMC) en pacientes miopes con o sin astigmatismo asociado. Método: Se realizó un estudio preexperimental del tipo antes y después, en el que fueron incluidos 81 pacientes (162 ojos) tratados con LASEK-MMC (65 pacientes) o PRK-MMC (16 pacientes) seguidos por tres meses. Se les realizó un examen oftalmológico completo y se evaluaron las variables: edad, sexo, diagnóstico y tipo de miopía, así como agudeza visual, esfera, cilindro, equivalente esférico precirugía y poscirugía. Además, se analizó la función visual y los resultados de la refracción. Resultados: El valor de la mediana de edad fue de 24,0 años en los pacientes tratados con LASEK-MMC y en el grupo con PRK-MMC fue de 23,0 años. En ambos grupos existió un predominio del sexo femenino. La totalidad de los pacientes tratados presentaba un astigmatismo miópico compuesto con niveles de miopía leve. A los tres meses el 96,9 por ciento de los pacientes tratados con LASEK-MMC y el 93,8 por ciento de los tratados con PRK-MMC tenían una agudeza visual no corregida de 20/20 o más y todos tenían una visión de 20/40 o más. Conclusiones: La cirugía fotoablativa con láser tiene buenos resultados refractivos y visuales ya que la mayoría de los pacientes quedaron emétropes con una marcada mejoría de la agudeza visual sin corrección y de la refracción en el posoperatorio(AU)

Objective: To evaluate refractive and visual outcomes after excimer laser corneal refractive surgery (laser-assisted subepithelial keratectomy [LASEK] or photorefractive keratectomy [PRK], with intraoperative application of mitomycin-C [MMC]) in myopic patients with or without associated astigmatism. Methods: A preexperimental, before-and-after study was carried out with 81 patients (162 eyes) treated with LASEK-MMC (65 patients) or PRK-MMC (16 patients) and followed for three months. A complete ophthalmologic examination was done and the following variables age, sex, diagnosis and type of myopia were assessed, as well as pre-surgery and post-surgery visual acuity, sphere, cylinder and spherical equivalent. In addition, visual function and the refraction results were analyzed. Results: The median age was 24.0 years in the LASEK-MMC group and 23.0 years in the PRK-MMC group. In both groups there was a predominance of the female sex. All treated patients had compound myopic astigmatism with mild myopia. At three months, 96.9 percent of patients treated with LASEK-MMC and 93.8 percent of patients treated with PRK-MMC had uncorrected visual acuity of 20/20 or better, and all had vision of 20/40 or better. Conclusions: Laser photoablative surgery has good refractive and visual outcomes as most patients became emmetropic with marked improvement in uncorrected visual acuity and refraction postoperatively(AU)

Modulating effect of a hydroxychalcone and a novel coumarin-chalcone hybrid against mitomycin-induced genotoxicity in somatic cells of Drosophila melanogaster.

Chalcones are aromatic compounds found in plants or obtained by synthetic methods. These compounds and their derivatives have been proven to be responsible for a variety of pharmacological properties, including anti-inflammatory and anticancer activities. A second interesting class of compound are coumarins which comprises a large class of molecules derived from phenolic compounds found mainly in plants, exhibiting multiple biological activities such as antioxidant and anti-tumoral properties. Due to the relevance of these compounds, this study aimed to investigate the genotoxic/antigenotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one (2HMC) and the coumarin-chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl)acryloyl-2H-cromen-2-one] (4-MET) using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To assess the mutagenic and recombinogenic activities, larvae derived from standard and high bioactivation crosses were treated with different concentrations of 2HMC (10, 50, 100 and 400 µg/mL) or 4-MET (5, 50, 100 and 400 µg/mL) for 48 h. Dimethylsulfoxide (DMSO, 0.5%) was the negative control group. The anti-recombinogenic and antimutagenic activities were assessed using larvae from both crosses co-treated with the same concentrations of 2HMC or 4-MET and mitomycin C (MMC, 0.05 mM). SMART revealed no mutagenic or recombinogenic effects since no significant increase of any category of mutant spots was observed (p > 0.05). However, both compounds reduced the frequency of all spots induced by MMC showing antimutagenic and anti-recombinogenic activities in D. melanogaster cells from both crosses. We suggest that the antimutagenic and anti-recombinogenic activities observed in our study may have been a result of the antioxidant activity of 2HMC and 4-MET.

Efficacy of mitomycin C in modified transcanalicular diode laser dacryocystorhinostomy / Eficácia da mitomicina C na dacriocistorrinostomia transcanalicular com laser diodo modificada

ABSTRACT Objective: To evaluate the efficacy of mitomycin C in anatomical and functional success after modified transcanalicular diode laser dacryocystorhinostomy. Methods: A prospective, double-blinded, randomized placebo-controlled study compared the effect of topical mitomycin C on modified transcanalicular diode laser dacryocystorhinostomy. Group 1 had modified transcanalicular diode laser dacryocystorhinostomy with topical saline, while Group 2 had modified transcanalicular diode laser dacryocystorhinostomy with topical mitomycin C. Success was defined as anatomical patency and relief of symptoms at the end of 6 months. Results: Six months after surgery, Group 1 (30 patients) showed anatomical and functional success rates of 86.7% and 83.3%, respectively. Group 2 (32 patients) showed anatomical and functional success rates of 87.5% and 84.3%, respectively. There was no statistically significant difference between the groups 1 and 2 (p = 1.000). Conclusion: The use of mitomycin C did not improve the anatomical and functional success rates of modified transcanalicular diode laser dacryocystorhinostomy compared to placebo.

RESUMO Objetivo: Avaliar a eficácia da mitomicina C no sucesso anatômico e funcional após dacriocistorrinostomia transcanalicular com laser de diodo. Métodos: Estudo prospectivo, duplo-cego, randomizado e controlado por placebo. Comparou o efeito da mitomicina C tópica na dacriocistorrinostomia transcanalicular com laser de diodo. No Grupo 1, foi utilizada apenas solução salina tópica, enquanto no Grupo 2 foi utilizada mitomicina C tópica. O sucesso foi definido como permeabilidade da via lacrimal e alívio dos sintomas ao final de 6 meses. Resultados: Seis meses após a cirurgia, o Grupo 1 (30 pacientes) apresentou taxas de sucesso anatômico e funcional de 86,7% e 83,3%, respectivamente. O Grupo 2 (32 pacientes) apresentou taxas de sucesso anatômico e funcional de 87,5% e 84,3%, respectivamente. Não houve diferença estatística significante entre os Grupos 1 e 2 (p=1,000). Conclusão: O uso de mitomicina C não melhora as taxas de sucesso anatômico e funcional do dacriocistorrinostomia transcanalicular com laser de diodo em comparação ao placebo.

Cirurgia Citorredutora com Quimioterapia Intraperitoneal Hipertérmica em Pacientes com Adenocarcinoma Mucinoso de Apêndice: Série de 43 Casos / Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Patients with Appendix Mucinous Adenocarcinoma: Series of 43 Casess / Cirugía Citorreductiva con Quimioterapia Intraperitoneal Hipertermal en Pacientes con Adenocarcinoma Mucinoso de Apéndice: Serie de 43 Caso

Introdução: O carcinoma primário de apêndice é uma condição rara. Muitas revisões retrospectivas internacionais delineiam a experiência de diferentes centros em neoplasias apendiculares. Por sua vez, o tratamento do câncer nessa localização é complexo e depende do subtipo histológico e da extensão da doença. Um dos tratamentos mais promissores é a cirurgia citorredutora (CCR) associada à quimioterapia intraperitoneal hipertérmica (HIPEC). No Brasil, não há descrição de séries de casos que tiveram essa abordagem terapêutica. O objetivo desta série de casos é analisar as características sociodemográficas e o tipo de intervenção terapêutica em pacientes com doenças malignas de apêndice em um Centro de Assistência de Alta Complexidade em Oncologia III (Cacon III). Relato dos casos: Foram incluídos 43 casos de tumores primários de apêndice. O adenocarcinoma do apêndice do tipo mucinoso de baixo grau foi a neoplasia mais diagnosticada. O principal protocolo utilizado foi de uma a duas cirurgias e aplicação de mitomicina C em temperatura média de 40 graus. Os casos apresentaram grande heterogeneidade quanto ao uso do protocolo. Conclusão: O presente relato de 43 casos é importante por se tratar de um tumor raro nessa localização. A modalidade terapêutica descrita é promissora, mas não há protocolo definido para essa finalidade. É necessário atualizar as diretrizes terapêuticas para normatizar a conduta internamente, especialmente em se tratando de uma unidade de referência nacional

Introduction: Primary appendix carcinoma is a rare condition. Many international retrospective reviews outline the experience of different centers in appendicular neoplasms. The cancer treatment in this location is complex and depends on the histological subtype and the extent of the disease. One of the most promising treatments is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In Brazil, there is no description of series of cases with this therapeutic approach. The purpose of this case series is to analyze the sociodemographic characteristics and the type of therapeutic intervention in patients with malignant diseases of the appendix in a High Complexity Care Center in Oncology III (Cacon III). Case reports: 43 cases of primary appendix tumors were included. Low-grade mucinous adenocarcinoma was the most diagnosed neoplasm. The main protocol used was 1 to 2 surgeries and application of mitomycin C at an average temperature of 40 degrees. There was great heterogeneity regarding the use of the protocol. Conclusion: The present report of 43 cases is important because it is a rare tumor with this location. The therapeutic modality described is promising, but there is no defined protocol for this purpose. It is necessary to update the therapeutic guidelines to standardize the conduct internally, especially in the case of a national reference unit

Introducción: El carcinoma primario de apéndice es una entidad poco frecuente. Numerosas revisiones retrospectivas internacionales describen la experiencia de diferentes centros en neoplasias apendiculares. A su vez, el tratamiento de esta localización del cáncer es complejo y depende del subtipo histológico y la extensión de la enfermedad. Uno de los tratamientos más prometedores es la cirugía citorreductora (CCR) asociada a quimioterapia intraperitoneal hipertérmica (HIPEC). En Brasil, no hay descripción de series de casos que tuvieran este abordaje terapéutico. El propósito de esta serie de casos es analizar las características sociodemográficas y el tipo de intervención terapéutica en pacientes con enfermedades malignas del apéndice en un Centro Asistencial de Alta Complejidad en Oncología III (Cacón III). Reporte de los casos: Se incluyeron 43 casos de tumores primarios de apéndice. El adenocarcinoma mucinoso de bajo grado tuvo la mayor incidencia. El protocolo principal utilizado fue de una a dos cirugías y aplicación de mitomicina C a una temperatura promedio de 40 grados. Los casos mostraron gran heterogeneidad en cuanto al uso del protocolo. Conclusión: El presente informe es importante porque es un tumor raro. La modalidad terapéutica descrita es prometedora, pero no existe un protocolo definido para tal fin. Es necesario actualizar las pautas terapéuticas para normalizar la conducta internamente, especialmente en el caso de una unidad de referencia nacional

Quistes subglóticos adquiridos: Reporte de tres casos y revisión de la literatura / Acquired subglottic cysts: Report of three cases and review of the literature

Los quistes subglóticos adquiridos son una causa rara de estridor en la infancia, cuyo reporte ha ido en aumento en las últimas décadas. Su aparición se relaciona con la prematurez y la intubación en el periodo neonatal. Histológicamente, se observa una obstrucción de las glándulas mucosas de la subglotis debido una metaplasia escamosa del epitelio respiratorio. Esta es una condición que usualmente requiere de un alto índice de sospecha para llegar al diagnóstico, ya que pueden confundirse con otras patologías como laringitis aguda (croup), laringomalacia o asma. La nasofibroscopía permite sospechar su presencia, pero el gold standard diagnóstico lo constituye la laringo-tra-queo-broncoscopía directa en pabellón. Existen diversas técnicas para su manejo, siendo las más frecuentemente utilizadas la marsupialización con instrumental frío y láser. La recurrencia es frecuente, por lo que algunos autores han utilizado mitomicina C y la terapia antirreflujo para intentar disminuirla. Sin embargo, hasta la fecha falta evidencia de calidad que permita llegar a un consenso respecto al manejo ideal de esta patología. En este trabajo, presentamos tres casos clínico de pacientes con antecedentes de prematurez que fueron diagnosticados con quistes subglóticos adquiridos y manejados en un hospital pediátrico de alta complejidad.

Acquired subglottic cysts are an infrequent cause of stridor in infants, which has been increasingly reported in the last decades. Its appearance is related to prematurity and intubation in the neonatal period. Histologically, findings are characterized by an obstruction of the mucosal glands, due to squamous metaplasia of the respiratory epithelium. This condition usually requires a high index of suspicion to be diagnosed, as it can be misdiagnosed as croup, laryngomalacia or asthma. Flexible nasendoscopy allows an initial exploration of the larynx, but direct laryngo-tracheo-bronchoscopy in the operating room is the diagnostic gold standard. There are several techniques for its management, but the most frequently used are cold-steel marsupialization and laser. Recurrence is common, and some authors have used mitomycin C and antireflux therapy to try to decrease it. However, up to date, there is a lack of high-quality evidence, regarding the ideal management of this pathology, which prevents reaching a consensus. In this article, we present three clinical cases of premature patients who were diagnosed with subglottic cysts, treated in a tertiary pediatric hospital.

Atresia de coana bilateral en adulto con malformación craneofacial asociada: un diagnóstico poco habitual / Bilateral choanal atresia in adult with associated craneofacial malformation: an unusual diagnosis

La atresia de coana es una rara malformación congénita improbable de encontrar de forma bilateral en un adolescente o adulto. Hasta la fecha, no se ha descrito ningún caso de atresia bilateral en un adulto con una malformación asociada de cabeza y cuello que haya requerido tratamiento conjunto. El tratamiento de elección de la atresia de coana bilateral continúa siendo la cirugía endoscópica, con controversia en el uso intraoperatorio de mitomicina o la colocación de stents para evitar estenosis. Lo que no está claro es el orden de tratamiento y la simultaneidad del procedimiento si se asocian otras posibles patologías que tengan una indicación quirúrgica. Presentamos un caso clínico que cumple con todos estos requisitos.

Choanal atresia is a rare congenital malformation that is unlikely to be found bilaterally and is seldom diagnosed in adulthood. To date, no clinical case of bilateral atresia has been described with a head and neck malformation that requires surgical treatment in an adult. The preferred treatment is still endoscopic sinonasal surgery with discrepancies of the use or not of intraoperative topical mitomycin or the placement of stents to avoid restenosis. What is not clear is the order of treatment and simultaneity of the procedure with other possible associated pathologies that have a surgical indication. We present a clinical case that meets all these requirements.

Resultados refractivos y visuales en pacientes operados de miopía con técnicas de superficies / Refractive and visual results in patients operated on for myopia with surface techniques

Objetivo: Comparar los resultados visuales y refractivos pre- y posoperatorios en pacientes miopes operados con técnicas de superficie y perfil de ablación asférico. Métodos: Se realizó un estudio experimental controlado aleatorizado abierto, tipo de equivalencia y no inferioridad, en 160 pacientes (320 ojos). En el estudio se formaron dos grupos: el primero quedó constituido por 80 pacientes (160 ojos), a quienes se les realizó queratectomía fotorrefractiva más mitomicina C, y el segundo fue conformado por 80 pacientes (160 ojos), a quienes se les realizó LASEK más mitomicina C. Resultados: Predominaron en ambos grupos las mujeres con miopía leve y edades entre 21 y 29 años. A los tres meses el grupo queratectomía fotorrefractiva más mitomicina C tenía agudeza visual sin corrección de 0,97 ± 0,09; esfera 0,003 ± 0,21; cilindro -0,09 ± 0,30 y equivalente esférico -0,04 ± 0,23. En el grupo LASEK más mitomicina C, la agudeza visual sin corrección fue de 0,96 ± 0,11; la esfera -0,007 ± 0,24; el cilindro -0,08 ± 0,25 y el equivalente esférico -0,06 ± 0,26. Conclusión: Ambas técnicas quirúrgicas mejoraron significativamente los resultados refractivos y visuales, pero no hubo diferencia entre ellas(AU)

Objective: Compare the pre- and postoperative visual and refractive results in myopic patients operated with surface techniques and aspheric ablation profile. Methods: An open randomized controlled experimental study, equivalence and non-inferiority type was carried out in 160 patients (320 eyes). In the study, two groups were formed: the first group was made up of 80 patients (160 eyes), who underwent Photorefractive keratectomy - mitomycin C, and the second group made up of 80 patients (160 eyes), underwent LASEK - mitomycin C. Results: Women with mild myopia and ages between 21 and 29 years old predominated in both groups. At three months, the Photorefractive keratectomy - mitomycin C group had AVSC 0.97 ± 0.09; sphere 0.003 ± 0.21; cylinder -0.09 ± 0.30 and spherical equivalent -0.04 ± 0, 2. 3. In the Photorefractive keratectomy - mitomycin C group, AVSC 0.96 ± 0.11; sphere -0.007 ± 0.24; cylinder -0.08 ± 0.25 and spherical equivalent -0.06 ± 0.26. Conclusion: Both surgical techniques improved significantly refractive and visual results, but there was no difference between them(AU)

Optimizing the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma / Otimização da dose efetiva da mitomicina C, do 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular

ABSTRACT Purpose: This study aimed to optimize the effective doses of mitomycin C, 5-fluorouracil, and their combination on cultivated basal cell carcinoma. Methods: Cultivated basal cell carcinoma and fibroblastic cells were treated with different concentrations of mitomycin C, 5-fluorouracil, and their combination. Cell viability, cell cycle, apoptosis, and expression levels of TP53, CDKN1A, and CDK6 were investigated. The most effective drug with its optimum dosage was administered via multiple intralesional injections to a 65-year-old woman with advanced periorbital nodulo-ulcerative BCC. Results: The concentrations of 0.00312 and 0.312 mg/mL were considered optimum for mitomycin C and 5-fluorouracil, respectively. The mean viabilities of basal cell carcinoma treated with mitomycin C alone and its combination with 5-fluorouracil were significantly less than those of the controls (p=0.002 and p=0.04, respectively). The cell cycle of all the treated basal cell carcinoma groups was arrested in the S phase. The apoptotic rates (p=0.002) of mitomycin C treated basal cell carcinoma were higher than those of the other treated cells, and their TP53 was significantly upregulated (p=0.0001). Moreover, CDKN1A was upregulated, whereas CDK6 was downregulated in basal cell carcinoma treated with either 5-fluorouracil (p=0.0001 and p=0.01, respectively) or the combination of 5-fluorouracil and mitomycin C (p=0.007 and p=0.001, respectively). Basal cell carcinoma lesions were significantly alleviated following mitomycin C injections in the reported patient. Conclusion: Our in vitro results revealed that the effective doses of mitomycin C and 5-fluorouracil on cultivated basal cell carcinoma were optimized. Mitomycin C was more effective in inducing the apoptosis of basal cell carcinoma than 5-fluorouracil and their combination. The intralesional injections of the optimum dose of mitomycin C could be proposed for the nonsurgical treatment of advanced eyelid basal cell carcinoma.

RESUMO Objetivo: Otimizar a dose efetiva de mitomicina C, 5fluorouracil e da combinação de ambos em culturas de células de carcinoma basocelular (CBC). Métodos: Culturas de células de células de carcinoma basocelular e de fibroblastos foram tratadas com diferentes concentrações de mitomicina C, 5fluorouracil e combinação de ambos. Além disto, foram investigados a viabilidade celular, o ciclo celular, a apoptose e a expressão dos genes TP53, CDKN1A e CDK6. O medicamento mais eficaz, em sua dosagem otimizada, foi administrado em últiplas injeções intralesionais em uma mulher de 65 anos com carcinoma basocelular nódulo-ulcerativo periorbital avançado. Resultados: A concentração de 0,00312 mg/mL de mitomicina C e a de 0,312 mg/mL de 5fluorouracil foram consideradas as ideias. A viabilidade média das células de carcinoma basocelular tratadas com mitomicina C isoladamente e em combinação foi significativamente menor que nas células de controle (respectivamente, p=0,002 e p=0,04). Todos os grupos de carcinoma basocelular tratados demonstraram interrupção do ciclo celular na fase S. As células de carcinoma basocelular tratadas com mitomicina C mostraram maiores taxas de apoptose (p=0,002) e significativa regulação positiva do gene TP53 (p=0,0001). Além disso, o gene CDKN1A foi positivamente regulado e o gene CDK6 foi negativamente regulado em células de carcinoma basocelular tratadas com 5fluorouracil (respectivamente, p=0,0001 e p=0,01) ou com a combinação de medicamentos (respectivamente, p=0,007 e p=0,001). Injeções posteriores de mitomicina C na paciente em questão levaram à melhora significativa da lesão do carcinoma basocelular. Conclusão: Nossos resultados in vitro otimizaram as doses efetivas de mitomicina C e 5fluorouracil na cultura de células de carcinoma basocelular e mostraram que a mitomicina C tem mais eficácia na apoptose de células de carcinoma basocelular do que o 5fluorouracil e a combinação de ambos. Injeções intralesionais de doses otimizadas de mitomicina C podem ser propostas para o tratamento não cirúrgico do células de carcinoma basocelular avançado de pálpebra.

Diferentes concentraciones de mitomicina C en la prevención del haze en la queratectomía fotorrefractiva / Different concentrations of mitomycin C for haze prevention in photorefractive keratectomy

Objetivo: Evaluar la utilidad de dos concentraciones de mitomicina C para la prevención del haze en la queratectomía fotorrefractiva. Métodos: Se realizó un estudio experimental aleatorizado en 26 ojos de 17 pacientes con defectos miópicos. Los pacientes fueron asignados a dos grupos según las dosis de mitomicina C (0,02 por ciento grupo 1 y 0,002 por ciento grupo 2). La variable de respuesta principal fue la presencia de haze. Se buscó correlación entre la magnitud del haze con grado de ametropía tratada, profundidad de ablación, microscopia endotelial y resultados visuales y refractivos. Resultados: A los 6 meses la mayoría de los pacientes del grupo 1 no presentó haze (ocho ojos / 57 por ciento), y del grupo 2 mantuvieron haze 0,5 (6 ojos / 50 por ciento). En la ametropía severa el haze en el grupo 2 fue mayor que en el grupo 1 durante todo el posoperatorio, y se observó la mayor diferencia al sexto mes con 0,5 ± 0,4 vs. 1,5 ± 0,32. En ablaciones > 75 micras el grupo dos terminó con más haze que el uno, con 0,5 ± 0,44 vs. 1,75 ± 0,76. La agudeza visual sin corrección se vio más afectada en el grupo 2. No hubo daño endotelial en ningún grupo. Conclusión: La presencia de haze predomina en los casos tratados con dosis 0,002 por ciento de mitomicina C, comparada con la dosis 0,02 por ciento, aunque en este caso ambos grupos mantuvieron un resultado visual y refractivo adecuado y baja toxicidad endotelial.

Objective: Evaluate the usefulness of two concentrations of mitomycin C for haze prevention in photorefractive keratectomy. Methods: An experimental randomized study was conducted of 26 eyes of 17 patients with myopic defects. The patients were divided into two groups according to their mitomycin C doses (Group 1: 0.02 percent and Group 2: 0.002 percent). The main response variable was the presence of haze. Verification was performed of the correlation between haze magnitude and the degree of the ametropia treated, ablation depth, endothelial microscopy, and visual and refractive results. Results: At six months most patients in Group 1 did not have any haze (eight eyes / 57 percent), whereas 0.5 (6 eyes / 50 percent) in Group 2 still had haze. In severe ametropia, haze was larger in Group 2 than in Group 1 throughout the postoperative period, the greatest difference being observed in the sixth month with 0.5 ± 0.4 vs 1.5 ± 0.32. In ablations > 75 microns, Group 2 ended with more haze than Group 1, with 0.5 ± 0.44 vs 1.75 ± 0.76. Uncorrected visual acuity was more affected in Group 2. No endothelial damage occurred in either group. Conclusion: The presence of haze prevails in cases treated with 0.002 percent doses of mitomycin C, as compared with 0.02 percent doses, though in this case both groups maintained an appropriate visual and refractive result and low endothelial toxicity(AU)

Mitochondrial Dysfunction and Alterations in Mitochondrial Permeability Transition Pore (mPTP) Contribute to Apoptosis Resistance in Idiopathic Pulmonary Fibrosis Fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by increased activation of fibroblasts/myofibroblasts. Previous reports have shown that IPF fibroblasts are resistant to apoptosis, but the mechanisms remain unclear. Since inhibition of the mitochondrial permeability transition pore (mPTP) has been implicated in the resistance to apoptosis, in this study, we analyzed the role of mitochondrial function and the mPTP on the apoptosis resistance of IPF fibroblasts under basal conditions and after mitomycin C-induced apoptosis. We measured the release of cytochrome c, mPTP opening, mitochondrial calcium release, oxygen consumption, mitochondrial membrane potential, ADP/ATP ratio, ATP concentration, and mitochondrial morphology. We found that IPF fibroblasts were resistant to mitomycin C-induced apoptosis and that calcium, a well-established activator of mPTP, is decreased as well as the release of pro-apoptotic proteins such as cytochrome c. Likewise, IPF fibroblasts showed decreased mitochondrial function, while mPTP was less sensitive to ionomycin-induced opening. Although IPF fibroblasts did not present changes in the mitochondrial membrane potential, we found a fragmented mitochondrial network with scarce, thinned, and disordered mitochondria with reduced ATP levels. Our findings demonstrate that IPF fibroblasts are resistant to mitomycin C-induced apoptosis and that altered mPTP opening contributes to this resistance. In addition, IPF fibroblasts show mitochondrial dysfunction evidenced by a decrease in respiratory parameters.

Starting a peritoneal carcinomatosis treatment program in a developing country: A prospective analysis.

BACKGROUND: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has become a valuable treatment strategy for selected patients with peritoneal carcinomatosis (PC). In Chile, it is an emerging technique. The aim of this study is to describe our protocol and report our perioperative results. METHODS: A prospectively maintained database for patients undergoing exploratory surgery for PC was reviewed. Eligible patients were selected using the peritoneal cancer index in correlation with the primary tumor. Patients underwent HIPEC using mitomycin C. Clinical data and postoperative results were analyzed. RESULTS: Seventy-six patients underwent exploratory surgery. Most patients were female (55%) with a median age of 62 years (range, 25-83). Complete CRS and HIPEC were achieved in 53 patients. The most frequent primary tumor site was colon-rectum (49%). The median number of resected organs was 4 (range, 1-13). Overall 90-day incidence of major complications was 26%. After a median follow-up of 26 months, 44 patients (83%) in the resected group were alive with no evidence of disease. CONCLUSIONS: The PC treatment program at our institution has been established in a safe manner, with acceptable morbidity comparable to high-volume centers. A comprehensive preoperative evaluation, careful patient selection, and a cohesive team are necessary for successful results.