Low-dose cisplatin exposure and SNAIL, Vimentin, E-cadherin expression in HEPG2 cell line / Exposición a dosis bajas de cisplatino y expresión de SNAIL, Vimentina, E-cadherina en línea celular HEPG2

Cisplatin, the first platinum compound approved for cancer treatment, is widely used in the treatment of various cancers including hepatocellular carcinoma (HCC). HCC incidence rates rise globally. Epithelial mesenchymal transition (EMT) is implicated in cancer invasion and metastasis, which are associated with increased mortality. Cisplatin dose might influence cancer invasion and metastatic behavior of the cells. The aim of the study was to investigate the effect of low-dose cisplatin treatment on EMT- related changes in HepG2 cells. Following treatment with 4 µM cisplatin, HepG2 cells were evaluated morphologically. Gene expression of E-cadherin, Vimentin, Snail1 was assessed by quantitative PCR. Immunofluorescence analyses of NA-K ATPase were performed. Although the low-dose cisplatin treated cells exhibited a more stretched morphology, no statistical difference was detected in gene expression of E-cadherin, Vimentin, Snail1 and immunofluorescence of NA-K ATPase. Findings on low-dose cisplatin effects in HepG2 might contribute to the knowledge of antineoplastic inefficacy by further understanding the molecular mechanisms of drug action.

El cisplatino, el primer compuesto de platino aprobado para el tratamiento del cáncer, es ampliamente utilizado en el tratamiento de varios tipos de cáncer, incluido el carcinoma hepatocelular (CHC). Las tasas de incidencia de CHC aumentan a nivel mundial. La transición mesenquimal epitelial (EMT) está implicada en la invasión del cáncer y la metástasis, que se asocian con un aumento de la mortalidad. La dosis de cisplatino podría influir en la invasión del cáncer y el comportamiento metastásico de las células. El objetivo del estudio fue investigar el efecto del tratamiento con dosis bajas de cisplatino en los cambios relacionados con la EMT en las células HepG2. Tras el tratamiento con cisplatino de 4 µM, se evaluaron morfológicamente las células HepG2. La expresión génica de E-cadherina, vimentina, caracol1 se evaluó mediante PCR cuantitativa. Se realizaron análisis de inmunofluorescencia de NA-K ATPasa . Aunque las células tratadas con cisplatino en dosis bajas exhibieron una morfología más estirada, no se detectaron diferencias estadísticas en la expresión génica de E-cadherina, vimentina, Snail1 e inmunofluorescencia de NA-K ATPasa. Los hallazgos sobre los efectos del cisplatino en dosis bajas en HepG2 podrían contribuir al conocimiento de la ineficacia antineoplásica al comprender mejor los mecanismos moleculares de la acción del fármaco.

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) en el tratamiento de la carcinomatosis peritoneal: primeros casos en Chile / PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) in the treatment of peritoneal carcinomatosis: first cases in Chile

Resumen Introducción: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) Es una técnica que, vía laparoscopía, permite administrar quimioterapia en aerosol intraperitoneal, para el tratamiento de la carcinomatosis, ya sea para disminuir masa tumoral y aumentar la resecabilidad, o como paliación sintomática. Objetivo: Presentar los dos primeros casos de PIPAC en Chile, las consideraciones técnicas y revisión de la literatura. Pacientes y Método: Se describe la forma en que un programa PIPAC fue implementado en Clínica Las Condes. Se describe la técnica. Este procedimiento se realizó en dos pacientes, ambas portadoras de carcinomatosis con ascitis refractaria. Resultados: No hubo complicaciones. Alta a las 24 h. Ambas pacientes presentaron disminución de la ascitis, la que se ha mantenido a los seis meses de seguimiento. Discusión: PIPAC es una técnica emergente, que ha demostrado ser segura, con escasas complicaciones, cuya indicación incluye carcinomatosis por cáncer de colon y ovario y que se está extendiendo a páncreas, vía biliar y estómago. Su rol exacto está por definirse. Conclusiones: PIPAC es una técnica factible de realizar en nuestro país; sus resultados preliminares son alentadores y exentos de complicaciones.

Introduction: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy is a technique that allows laparoscopic administration of aerosol chemotherapy in the peritoneum. This procedure is utilized for treatment of carcinomatosis, for debulk abdominal tumors, increasing resectability, or for palliation of abdominal symptoms. Aim: To present the first two cases of PIPAC performed in Chile, technical considerations and review of the literature. Patients and Method: The way this program was started at Clínica Las Condes is presented. The technique is described. This procedure was performed in two females, both with refractory ascites due to carcinomatosis. Results: The procedure was uneventfully and patients were discharged 24 hours later. Both patients showed important reduction of ascites, maintained at 6 months of followup. Discussion: PIPAC is a safe emerging technique, with low complication rate. It is indicated in carcinomatosis of colonic and ovarían origin and in selected cases of pancreatic, bile duct and gastric carcinomatosis. More prospective, randomized studies should be done to stablish its exact role. Conclusions: PIPAC is a feasible technique to perform in our country. Preliminary results are encouraging and no complications were observed.

Cáncer escamoso asentado sobre sinus pilonidal recurrente: la evolución de una patología benigna y frecuente a una causa de muerte infrecuente / Squamous cancer settled on recurrent pilonidal sinus: the evolution of a benign and frequent pathology to an infrequent cause of death

El sinus pilonidal es una patología frecuente cuya malignización es infrecuente aunque su pronóstico puede ser fatal. El objetivo de esta publicación es presentar un caso de un paciente intervenido en múltiples ocasiones de escisiones de sinus pilonidal con degeneración maligna del mismo y evolución fatal, con el fin de recalcar la importancia del examen anatomopatológico sistemático de todas las muestras de escisión quirúrgica. (AU)

The pilonidal sinus is a frequent pathology whose malignization is uncommon although its prognosis can be fatal. The objective of this publication is to present a case of a patient intervened on multiple occasions of pilonidal sinus excisions with malignant degeneration and fatal evolution, in order to emphasize the importance of the systematic pathological examination of all surgical excision samples. (AU)

First - line, non - cryopreserved autologous stem cell transplant for poor - risk germ - cell tumors: Experience in a developing country

ABSTRACT Purpose: The current first - line treatment for non - seminomatous germ cell tumor (NSGCT) consists of four cycles of cisplatin, etoposide, and bleomycin (BEP), which results in 5 - year overall survival < 60% in patients with poor - risk features. Autologous hematopoietic stem cell transplantation (auto - HSCT) as a method for overcoming high toxicity after high dose chemotherapy (HDC) has been explored in different solid tumors, but has remained standard practice only for NSGCT. Our objective was to describe outcomes of patients with poor - risk NSGCT who underwent first - line autologous HSCT in a tertiary center in Mexico. Patients and Methods: Twenty nine consecutive patients with NSGCT who received first - line, non - cryopreserved autologous HSCT at the National Institute of Medical Sciences and Nutrition Salvador Zubiran in Mexico City, Mexico, from November 1998 to June 2016, were retrospectively analyzed. Results: The median age at transplantation was 23 (15 - 39) years. Most patients (n = 18, 62%) had testicular primary tumor, and 23 had metastases (79%). Complete response after auto - HSCT was observed in 45%. Non - relapse mortality was 0. Five - year relapse / progression free and overall survival were 67% and 69%, respectively. Conclusions: This small single limited - resource institution study demonstrated that patients with poor - risk NSGCT are curable by first - line HDC plus autologous HSCT and that this procedure is feasible and affordable to perform using non - cryopreserved hematopoietic stem cells.

Experience in intra-arterial chemotherapy using two protocols for the treatment of OSCC over two decades at the University Hospital Vienna

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.

Efficacy and toxicity of concurrent chemoradiation in inoperable oral carcinoma in pakistani population

Objective: To evaluate the efficacy of concurrent Chemoradiation in patients with locally advanced inoperable squamous cell carcinoma of oral cavity in terms of local control and toxicity

Study Design: Case series

Place and Duration of Study: Institute of Nuclear Medicine and Oncology [INMOL], Lahore, from January 2008 to December 2013

Methodology: Sixty-nine patients with locally advanced inoperable oral cavity cancer, registered in INMOL hospital from January 2008 to December 2013 who fulfilled a pre-defined eligibility criteria, were enrolled in the study

Concurrent Chemoradiation protocol consisted of conventional fractionation delivering 70 Gy with weekly Cisplatin [50 mg/m[2]] during the course of radiation

Tumor response was calculated by RECIST criteria version 1.1 along with the median overall survival and disease-free survival. Acute treatment related toxicities were graded as [G]

Results: Thirty-six [52.17%] patients showed complete response; while 19 [27.54%], 8 [11.59%] and 6 [8.7%] were observed with partial response, stable and progressive disease, respectively. Treatment response was significant [p<0.001] in terms of responders vs. nonresponders to treatment. Median overall survival was 18.00 months; whereas, median disease-free survival remained 14.00 months. Main toxicities included mucositis [G3 and G4, 71%], xerostomia [G2 and G3, 82.5%], vomiting [G3 and G4, 51%], myelosuppression [G3 and G4, 26.2%], dermatitis [G3 and G4, 49.2%], and fatigue [G3 and G4, 57.9%]

Conclusion: Platinum based CCRT remained effective for inoperable oral cancer patients

New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years

OBJECTIVE: The aim of this study was to summarize the experience of a tertiary center in treating hepatoblastoma for the last 21 years. PATIENTS AND METHODS: Fifty-eight cases were included. The tumor extent and prognosis were assessed using the PRETEXT system. The following data were analyzed: age at diagnosis, comorbidities, prematurity, treatment modalities, histopathological findings, surgical details and complications, treatment outcomes, chemotherapy schedules, side effects and complications. Treatment outcomes included the occurrence of local or distant recurrence, the duration of survival and the cause of death. The investigation methods were ultrasonography, CT scan, serum alpha-fetoprotein level measurement and needle biopsy. Chemotherapy was then planned, and the resectability of the tumor was reevaluated via another CT scan. RESULTS: The mean numbers of neoadjuvant cycles and postoperative cycles of chemotherapy were 6±2 and 1.5±1.7, respectively. All children except one were submitted for surgical resection, including 50 partial liver resections and 7 liver transplantations. Statistical comparisons demonstrated that long-term survival was associated with the absence of metastasis (p=0.04) and the type of surgery (resection resulted in a better outcome than transplantation) (p=0.009). No associations were found between vascular invasion, incomplete resection, histological subtype, multicentricity and survival. The overall 5-year survival rate of the operated cases was 87.7%. CONCLUSION: In conclusion, the experience of a Brazilian tertiary center in the management of hepatoblastoma in children demonstrates that long survival is associated with the absence of metastasis and the type of surgery. A multidisciplinary treatment involving chemotherapy, surgical resection and liver transplantation (including transplantations using tissue from living donors) led to good outcomes and survival indexes. .

Agregação familiar da doença renal crônica secundária à hipertensão arterial ou diabetes mellitus: estudo caso-controle / Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study

No Brasil, a hipertensão e o diabetes mellitus tipo 2 são responsáveis por 60% dos casos de doença renal crônica terminal em terapia renal substitutiva. Estudos americanos identificaram agregação familiar da doença renal crônica, predominante em afrodescendentes. Um único estudo brasileiro observou agregação familiar entre portadores de doença renal crônica quando comparados a indivíduos internados com função renal normal. O objetivo deste artigo é avaliar se existe agregação familiar da doença renal crônica em familiares de indivíduos em terapia renal substitutiva causada por hipertensão e/ou diabetes mellitus. Estudo caso-controle tendo como casos 336 pacientes em terapia renal substitutiva portadores de diabetes mellitus ou hipertensão há pelo menos 5 anos e controles amostra pareada de indivíduos com hipertensão ou diabetes mellitus e função renal normal (n = 389). Os indivíduos em terapia renal substitutiva (casos) apresentaram razão de chance de 2,35 (IC95% 1,42-3,89; p < 0,001) versus controles de terem familiares com doença renal crônica terminal, independente da raça ou doença de base. Existe agregação familiar da doença renal crônica na amostra estudada e esta predisposição independe da raça e da doença de base (hipertensão ou diabetes mellitus).

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer / 부인종양

OBJECTIVE: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. METHODS: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. RESULTS: In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.

Efficacy and tolerability of paclitaxel, ifosfamide, and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical carcinoma / 부인종양

OBJECTIVE: To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma. METHODS: Patients with histologically confirmed locally advanced cervical carcinoma, aged > or =18 years, were treated with intravenous ifosfamide 5,000 mg/m2 and mesna 5,000 mg/m2, on day 1; intravenous paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy. RESULTS: One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively. CONCLUSION: Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study / 부인종양

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51+/-9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73+/-5.51 days and the mean hospitalization time was 24.0+/-10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

Efecto otoprotector de N acetilcisteína en pacientes sometidos a quimioterapia con cisplatino: revisión de la literatura / Cytoprotective effect of N acetylcysteine patients undergoing chemotherapy cisplatin: literature review

The aim of this publication is to update information regarding auditory damage caused by cisplatin and its possible prevention with N acetylcysteine (NAC). Cisplatin is a drug used in the treatment of various cancers. It has various adverse effects including ototoxicity. Ototoxicity manifests as sensorineural high tone hearing loss variable intensities, usually bilateral, irreversible, and occurs primarily owing to the formation of oxygen derived free radicals that trigger apoptosis. High frequency audiometry and distortion-product otoacoustic emissions are the most sensitive tests for the detection of cisplatin ototoxicity and they are comparable. NAC is a thiol compound used as a mucolytic that can prevent ototoxicity by several mechanisms . In vitro, it has been shown to decrease the damage of inner ear hair cells and auditory neurons . In humans, oral and intratympanic NAC has been tested concomitant to cisplatin chemotherapy with variable results, tending to show less hearing damage produced by cisplatin...

Effect of 4-(N,N-dimethylamino)phenethyl Alcohol on Degree of Conversion and Cytotoxicity of Photo-Polymerized CQ-Based Resin Composites

The aim of this study was to evaluate the degree of conversion (DC) and the cytotoxicity of photo-cured experimental resin composites containing 4-(N,N-dimethylamino)phenethyl alcohol (DMPOH) combined to the camphorquinone (CQ) compared with ethylamine benzoate (EDAB). The resin composites were mechanically blended using 35 wt% of an organic matrix and 65 wt% of filler loading. To this matrix was added 0.2 wt% of CQ and 0.2 wt% of one of the reducing agents tested. 5x1 mm samples (n=5) were previously submitted to DC measurement and then pre-immersed in complete culture medium without 10% (v/v) bovine serum for 1 h or 24 h at 37 °C in a humidifier incubator with 5% CO2 and 95% humidity to evaluate the cytotoxic effects of experimental resin composites using the MTT assay on immortalized human keratinocytes cells. As a result of absence of normal distribution, the statistical analysis was performed using the nonparametric Kruskal-Wallis to evaluate the cytotoxicity and one-way analysis of variance to evaluate the DC. For multiple comparisons, cytotoxicity statistical analyses were submitted to Student-Newman-Keuls and DC analysis to Tukey's HSD post-hoc test (=0.05). No significant differences were found between the DC of DMPOH (49.9%) and EDAB (50.7%). 1 h outcomes showed no significant difference of the cell viability between EDAB (99.26%), DMPOH (94.85%) and the control group (100%). After 24 h no significant difference were found between EDAB (48.44%) and DMPOH (38.06%), but significant difference was found compared with the control group (p>0.05). DMPOH presented similar DC and cytotoxicity compared with EDAB when associated with CQ.

O objetivo deste estudo foi avaliar o grau de conversão (GC) e a citotoxicidade de resinas compostas experimentais utilizando o álcool 4-(N,N-dimetilamino) fenil etílico (DMPOH) associado à canforoquinona (CQ) como sistema fotoiniciador (SF) comparado à versão comercial utilizando o benzoato de etilamina (EDAB). Para tanto, as resinas compostas experimentais foram mecanicamente misturadas utilizando (em peso): 35% de matriz orgânica e 65% em peso de partículas de carga. Posteriormente, foram adicionados 0,2% de CQ e 0,2% de um dos agentes redutores testados. Amostras de 5 x 1 mm (n=5) foram previamentes submetidas à análise de GC e posteriormente, esterilizadas e colocadas no meio de cultura completo sem soro fetal bovino estéril por 1 h ou 24 h a 37 °C em encubadora com 5% de CO2 and 95% de umidade para avaliar os efeitos citotóxicos das resinas compostas experimentais utilizando o método MTT emcélulas células humanas imortalizadas de queratinócitos. Os dados de citotoxicidade foram submetidos à análise estatística de Kruskal-Wallis e de GC à análise de variância com um fator. Em virtude da ausência de normalidade, a análise estatística da citotoxicidade foi realizada utilizando-se o teste não-paramétrico de Kruskal-Wallis. Para o GC, os dados foram submetidos à análise de variaância de 1 fator. Posteriormente para múltiplas comparações, os dados de citotoxicidade foram submetidos ao teste Student-Newman-Keuls e o GC ao teste de Tukey's HSD post-hoc (=0.05). Não foi observada diferença estatística entre o GC de DMPOH (49,9%) e EDAB (50,7%). Para os resultados de 1 h não houve diferença na viabilidade celular entre EDAB (99,26%), DMPOH (94,85%) e o grupo controle (100%). Após 24 h, nenhuma diferença estatística foi encontrada entre EDAB (48,44%) e DMPOH (38,06%), entretanto, diferença significativa foi encontrada em relação ao grupo controle (p>0,05). O DMPOH apresentou GC e citotoxicidade semelhante à EDAB quando associado à CQ.

Efeitos da sondagem nasogástrica em pacientes com acidente cerebrovascular e disfagia / Effects of nasogastric catheterization in patients with stroke and dysphagia / Efectos de la cateterización nasogástrica en pacientes con accidente cerebrovascular y disfagia

O estudo teve por objetivo analisar os efeitos da sondagem gástrica em pacientes com acidente vascular cerebral e disfagia. Revisão sistemática da literatura, realizada em seis bases de dados, com os descritores stroke e intubation, gastrointestinal. Foram encontrados 120 estudos e selecionados três ensaios clínicos. Os resultados apontaram diferentes desfechos, entre os quais: aumento do nível sérico de albumina (gastrostomia), prognóstico ruim e risco de morte (gastrostomia), aumento das falhas no tratamento devido a bloqueio, deslocamento e reinserção da sonda nasogástrica, e aumento da incidência de hemorragia gastrointestinal (sonda nasogástrica). A partir dos resultados obtidos nesta revisão sistemática, ressaltam-se as seguintes evidências: a sondagem nasogástrica deve ser adotada precocemente como um método de alimentação enteral; as falhas do tratamento são mais comuns naqueles que utilizam a sonda nasogástrica como método de alimentação; os resultados relacionados à melhora do estado funcional dos pacientes foram semelhantes, independente do método de terapia nutricional empregado.

This study aimed to analyze the effects of gastric intubation in patients with stroke and dysphagia. A systematic literature review was performed in six databases, using the keywords stroke and intubation, gastrointestinal. One hundred and twenty studies were found, from which three clinical trials were selected. The results showed different outcomes, including: increased serum albumin level (gastrostomy), poor prognosis and risk of death (gastrostomy), increased treatment failures because of blocking, displacement and reinsertion need of the nasogastric tube, and increased incidence of gastrointestinal bleeding (nasogastric tube). From the results obtained in this systematic review, we emphasize the following evidences: a nasogastric catheter should be adopted as a method of early enteral feeding; treatment failures are more common in those who use nasogastric tube-feeding; outcomes related to improved functional status of patients were similar, regardless of the method of nutritional therapy used.

El objetivo del estudio fue analizar los efectos de la intubación gástrica en pacientes con accidente cerebrovascular y disfagia. Se llevó a cabo una revisión sistemática de la literatura en seis bases de datos, utilizando-se las palabras clave accidente cerebrovascular y intubación, gastrointestinal. Entre 120 estudios identificados, fueran seleccionados tres ensayos clínicos. Los resultados mostraron diferentes desfechos, incluyendo: aumento del nivel de albúmina sérica (gastrostomía); mal pronóstico y riesgo de muerte (gastrostomía); aumento de los fracasos del tratamiento debido a obstrucción, desplazamiento y necesidad de reinserción de la sonda nasogástrica; y aumento de la incidencia de hemorragia gastrointestinal (sonda nasogástrica). A partir de los resultados obtenidos, destacamos las siguientes evidencias: se deben adoptar catéteres nasogástricas como método de alimentación enteral temprana; fracasos del tratamiento son más comunes en aquellos que utilizan la alimentación con sonda nasogástrica; los resultados relacionados con la mejora del estado funcional de los pacientes fueron similares, independientemente del método de terapia nutricional utilizado.

Liver cancer stem cells are selectively enriched by low-dose cisplatin

Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs). Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 μg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT) assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1) and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 μg/mL cisplatin, whereas 5 μg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.

Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center.

BACKGROUND: Recent studies indicate neoadjuvant chemotherapy (NACT) can result in R0 resection in a substantial proportion of patients with technically unresectable oral cavity cancers. However, data regarding the efficacy and safety of docetaxel, cisplatin and 5 fluorouracil (TPF) NACT in our setting is lacking. The present audit was proposed to evaluate the toxicities encountered during administration of this regimen. It was hypothesized that TPF NACT would be considered feasible for routine administration if an average relative dose intensity (ARDI) of ≥0.90 or more in at least 70% of the patients. MATERIALS AND METHODS: Technically unresectable oral cancers with Eastern Cooperative Oncology Group PS 0-2, with biopsy proven squamous cell carcinoma underwent two cycles of NACT with TPF regimen. Toxicity and response rates were noted following the CTCAE 4.03 and RECIST criteria. Descriptive analysis of completion rates (completing 2 cycles of planned chemotherapy with ARDI of 0.85 or more), reason for delay, toxicity, and response are presented. RESULTS: The NACT was completed by all patients. The number of subjects who completed all planned cycles of chemotherapy are with the ARDI of the delivered chemotherapy been equal to or >0.85 was 11 (91.67%). All toxicity inclusive Grade 3-5 toxicity was seen in 11 patients (91.67%). The response rate of chemotherapy was 83.33%. There were three complete response, seven partial response, and two stable disease seen post NACT in this study. CONCLUSION: Docetaxel, cisplatin and 5 fluorouracil regimen can be routinely administered at our center with the supportive care methods and precautionary methods used in our study.

Concurrent Chemoradiotherapy Shows Long-Term Survival after Conversion from Locally Advanced to Resectable Hepatocellular Carcinoma

PURPOSE: For locally unresectable hepatocellular carcinoma (HCC) patients, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment. After shrinkage of tumors in selected patients, surgical resection is performed. The aim of this study was to evaluate prognostic factors and long-term survivors in such patients. MATERIALS AND METHODS: From January 2000 to January 2009, 264 patients with HCC were treated with CCRT (45 Gy with fractional dose of 1.8 Gy), and intra-arterial chemotherapy was administered during radiotherapy. Eighteen of these patients (6.8%) underwent hepatic resection after showing a response to CCRT. Cases were considered resectable when tumor-free margins and sufficient remnant volumes were obtained without extrahepatic metastasis. Prior to operation, there were six patients with complete remission, 11 with partial remission, and six with stable disease according to modified Response Evaluation Criteria in Solid Tumors. RESULTS: In pathologic review, four patients (22.2%) showed total necrosis and seven patients (38.9%) showed 70-99% necrosis. A high level of necrosis (> or =80%) was correlated with low risk for extrahepatic metastasis and long-term survival. In univariate analyses, vessel invasion and capsular infiltration were significantly correlated with disease free survival (DFS) (p=0.017 and 0.013, respectively), and vessel invasion was significantly correlated with overall survival (OS) (p=0.013). In multivariate analyses, capsule infiltration was a significant factor for DFS (p=0.016) and vessel invasion was significant for OS (p=0.015). CONCLUSION: CCRT showed favorable responses and locally advanced HCC converted into resectable tumor after CCRT in selected patients. Long-term survivors showed the pathological features of near total necrosis, as well as negative capsule and vessel invasion.

Long-Term Outcome of Photodynamic Therapy with Systemic Chemotherapy Compared to Photodynamic Therapy Alone in Patients with Advanced Hilar Cholangiocarcinoma

BACKGROUND/AIMS: Patients with cholangiocarcinoma usually present at an advanced stage, and more than 50% of cases are not resectable at the time of diagnosis. Recently, photodynamic therapy (PDT) has been proposed as a palliative and neoadjuvant modality. We evaluated whether combination of PDT and chemotherapy is more effective than PDT alone. METHODS: In total, 161 patients with cholangiocarcinoma diagnosed between February 1999 and September 2009 were evaluated. Sixteen patients were treated with PDT and chemotherapy (group A), and 58 were treated with PDT (group B). RESULTS: The median survival was 538 days (95% confidence interval [CI], 475.3 to 600.7) in group A and 334 days (95% CI, 252.5 to 415.5) in group B (p=0.05). Lymph node metastasis status, serum bilirubin of pretreatment, tumor node metastasis stage, treatment method (PDT with chemotherapy vs PDT alone), time to PDT and the number of PDT sessions were prognostic factors with statistical significance in the univariate analysis. A multivariate analysis showed that PDT with chemotherapy and more than two sessions of PDT were significant independent predictors of longer survival in advanced cholangiocarcinoma (hazard ratio [HR], 2.23; 95% CI, 1.18 to 4.20; p=0.013 vs HR, 1.79; 95% CI, 1.044 to 3.083; p=0.034). CONCLUSIONS: PDT with chemotherapy results in longer survival than PDT alone.

ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer

PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.