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Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures from 25/27 human BC samples, in which the ability of growth in vitro replicates the clinical and biological aggressiveness of the original tumors. According to the results of next generation sequencing analysis, a direct correlation was found between PI3KA mutations and the sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents. Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS and BRAF, were found in resistant samples, suggesting their potential role as negative predictive factors of response to these agents. Thus, we demonstrated that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug screening for chemotherapies and targeted agents in genetically selected patients and represent an innovative model to identify new biomarkers of drug resistance.
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Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Resistencia a Antineoplásicos/genética , Imidazoles/farmacología , Oxazepinas/farmacología , Piperazinas/farmacología , Pirimidinas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Moduladores de Tubulina/farmacologíaRESUMEN
BACKGROUND: To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. METHODS: We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. RESULTS: All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. CONCLUSIONS: In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.
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Increased insulin-like growth factor (igf) signalling has been observed in breast cancer, including endocrine-responsive cancers, and has been linked to disease progression and recurrence. In particular, igf-1 has the ability to induce and promote lymphangiogenesis through the induction of vascular endothelial growth factor C (vegfc). In the present study, we analyzed serum and tumour samples from 60 patients with endocrine-positive breast cancer to determine the expression and the possible relationship of circulating igf-1, igf binding protein 3 (igfbp3), and vegfc with the presence of lymphatic metastasis and other immunohistochemical parameters. The analysis revealed a clear and significant correlation between high basal levels of igf-1, igfbp3, and vegfc and lymph node metastasis in endocrine-responsive breast cancer. In addition, expression of those molecules was significantly higher in breast cancer patients than in healthy control subjects. Those findings may enable more accurate prediction of prognosis in patients with breast cancer.
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This pooled analysis was performed using individual patient data from three phase II trials that included on the whole 113 esophageal cancer treated preoperatively with chemoradiotherapy (CRT), in order to analyze the efficacy and survival outcomes according to the achievement of the pathologic complete response (pCR). Thirty-nine patients were treated with 5-fluorouracil/cisplatin and RT (40 Gy), 33 patients received paclitaxel/cisplatin weekly during weeks 1-6 with and RT (46 Gy), 41 patients were treated with induction bio-chemotherapy with cetuximab and FOLFOX-4 followed by concomitant cetuximab and RT of 50.4 Gy. One hundred and two out of 113 resected patients were included in the survival analysis. The median overall survival (OS) time for the whole population was 21.5 months. The 12, 24, and 36 months OS rates were 85.4, 45.2, and 33%, respectively. The difference in survival probability between patients with pCR and patients with partial response or stable disease after treatment was significant (P= 0.0002, hazard ratios = 0.21, 95% CI 0.18-0.60). On multivariate analysis, the pathologic response and histology were the only covariates independently associated with OS (P= 0.0157 and P= 0.0212, respectively). In our series, complete responder patients had a significant longer survival probability after treatment when compared to patients with partial response or stable disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Cisplatino/uso terapéutico , Neoplasias Esofágicas/terapia , Fluorouracilo/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Inducción de Remisión , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer (CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naïve patients with metastatic CRC.
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Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Receptores ErbB/inmunología , Animales , Anticuerpos Monoclonales Humanizados , Cetuximab , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Humanos , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
AIM: We retrospectively studied clinical picture, diagnosis, treatment and complications of patients with cervico-mediastinal goiter who underwent surgery. METHODS: Sixty-three patients underwent surgical treatment for cervico-mediastinal goiter in the last 10 years. Thirty-two patients (50.8%) had cervico-mediastinal goiter, 24 patients (33.3%) had mediastino-cervical goiter and 7 patients (11.1%) had mediastinal goiter. Forty-seven cases were prevascular goiters and 16 were retrovascular goiters. We performed total thyroidectomy in 25 patients, subtotal thyroidectomy in 31 patients and in 7 cases the resection of residual goiter. In 50 patients we used a cervical approach, in 12 patients the cervical incision was combined with median sternotomy (6 in total) and in 1 patient with transverse sternotomy. RESULTS: Three patients (4.7%) died in the postoperative period (2 cardio-respiratory failure and 1 pulmonary embolism). The histologic study revelead 5 (7.9%) carcinomas. Postoperative complications were: dyspnea in 7 cases (11.1%), transient vocal cord paralysis in 5 patients (7.9%), temporary hypoparathyroidism in 6 patients (9.5%) and kidney failure in 1 case (1.6%). CONCLUSIONS: Cervicotomy is the approach of choice but in some limited cases (carcinoma, thyroiditis, retrovascular goiter, ectopic goiter) the sternotomy should be performed. Postoperative mortality and morbidity is very low, independent of surgical techniques.
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The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Compuestos Organoplatinos/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células en Anillo de Sello/tratamiento farmacológico , Esquema de Medicación , Femenino , Fluorouracilo/efectos adversos , Humanos , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Compuestos Organoplatinos/efectos adversos , Neoplasias Gástricas/patología , Tasa de SupervivenciaRESUMEN
Ependymomas outside the confines of the cranium and spinal cord are rare. Direct extension into the soft tissues of the sacrococcygeal area may occur from a primary ependymoma of the spinal cord, cauda equina or filum terminale. Alternatively they may occur as a primary pre-sacral, pelvic and abdominal tumour, or as a primary tumour of the skin and subcutaneous tissue of the sacrococcygeal area without any demonstrable connection with the spinal cord. The Authors report a case of myxopapillary ependymoma of the ischioanal fossa, demonstrated by MRI. To our knowledge, our case is the first lesion reported at this site.
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Ependimoma/diagnóstico , Neoplasias de la Médula Espinal/diagnóstico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum effects are still controversial. The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy. METHODS: In this study, 15 patients were assigned randomly to three groups according to the surgical procedure to be used: open cholecystectomy (OC), CO2 pneumoperitoneum cholecystectomy (PP), and laparoscopic gasless cholecystectomy (abdominal wall lifting [AWL]), respectively. A pulmonary artery catheter was used for hemodynamic monitoring in all patients. A subcutaneous multiplanar device (Laparo Tenser) was used for abdominal wall lifting. To avoid misinterpretation of results, conventional anesthesia was performed with all parameters, and the position of the patients held fixed throughout surgery. The following parameters were analyzed: mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), systemic vascular resistances index (SVRI), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistances index (PVRI), peak inspiratory pressure (PIP), end-tidal CO2 pressure (ETCO)2, CO2 arterial pressure (PaCO2), and arterial pH. RESULTS: All the operations were completed successfully. The Laparo Tenser allowed good exposition of the surgical field. A slight impairment of the cardiopulmonary functions, with reduction of SVRI, MAP, and CI and elevation of pulmonary pressures and vascular resistance, followed induction of anesthesia. However, these effects tended to normalize in the OC and AWL groups over time. In contrast, CO2 insufflation produced a complex hemodynamic and pulmonary syndrome resulting in increased right- and left side filling pressures, significant cardiac index reduction, derangement of the respiratory mechanics, and respiratory acidosis. All of these effects normalized after desufflation. CONCLUSIONS: Cardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery. Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions. In high-risk patients, gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations.
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Músculos Abdominales , Colecistectomía/efectos adversos , Hemodinámica/fisiología , Pulmón/fisiología , Neumoperitoneo Artificial/efectos adversos , Adulto , Análisis de Varianza , Anestesia General/métodos , Presión Sanguínea , Índice de Masa Corporal , Dióxido de Carbono/administración & dosificación , Presión Venosa Central , Colecistectomía/métodos , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Neumoperitoneo Artificial/métodos , Arteria Pulmonar/fisiología , Presión Esfenoidal Pulmonar , Volumen Sistólico , Instrumentos Quirúrgicos , Resistencia VascularRESUMEN
The development of thyroid tissue can occur in any moment of the migration of the thyroid along the thyroglossal duct from the tongue, resulting in lingual (at tongue base), sublingual (below the tongue), prelaryngeal (in front of the larynx), and substernal (in the mediastinum) ectopy. Thyroglossal duct cyst is the most common type of clinical abnormality related to thyroid ectopy. Surgical removal of such ectopic tissue is justified since some Authors describe thyroid cancer arising from aberrant thyroid tissue. The Authors report a case of thyroid ectopy in a patient who underwent 20 years before a left thyroid resection with isthmectomy; during the operation the surgeon described a hypertrophic pyramidal lobe which was left in situ and the patients did not receive any hormone suppressing therapy.
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Coristoma , Quiste Tirogloso , Femenino , Humanos , Persona de Mediana Edad , Glándula Tiroides , TiroidectomíaRESUMEN
Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to regulate immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. A poor prognosis in patients with multiple myeloma, renal cell carcinoma, ovarian cancer, or prostate cancer has been associated consistently with elevated IL-6 serum levels. The aim of this study was, therefore, to assess IL-6 serum levels in 68 advanced gastrointestinal cancer patients and to correlate them with prognosis. IL-6 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, patients with disseminated cancer displayed significantly higher IL-6 serum levels than patients without apparent metastases. On univariate analysis, both overall survival (OS) and time to disease progression (TTP) were shown to be affected by IL-6 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-6 serum levels while confirming the role of previously established variables, such as performance status, carcinoembryonic antigen (CEA) serum levels, and distant metastases. In conclusion, this study showed that IL-6 serum levels were elevated in advanced gastrointestinal cancer patients and correlated with both OS and TTP. However, they were shown not to be an independent prognostic factor.
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Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Interleucina-6/sangre , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores Sexuales , Neoplasias Gástricas/sangre , Neoplasias Gástricas/tratamiento farmacológico , Tasa de SupervivenciaRESUMEN
The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.
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Cromosomas Humanos Par 18 , Neoplasias Colorrectales/genética , ADN de Neoplasias/genética , Pérdida de Heterocigocidad , Invasividad Neoplásica/genética , Polimorfismo de Nucleótido Simple , Alelos , Teorema de Bayes , Neoplasias Colorrectales/patología , Humanos , Funciones de Verosimilitud , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa/métodosRESUMEN
The study evaluates the role of radio-guided surgery (RGS) with 111In-octreotide in the treatment of lung neoplasms. RGS with octreotide appears to be useful in surgery, above all during the intraoperative staging of the tumour; it can define with greater precision the extent of the resections extended towards the lung wall and ensure a radical approach in minimal lung resections.
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Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Octreótido/análogos & derivados , Radiofármacos , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , CintigrafíaRESUMEN
Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P = 0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
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Adenocarcinoma/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Células Escamosas/sangre , Interleucina-2/sangre , Neoplasias Pulmonares/sangre , Proteínas de Neoplasias/sangre , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/inmunología , Adenocarcinoma/mortalidad , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Ensayo de Inmunoadsorción Enzimática , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Tablas de Vida , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Análisis de Supervivencia , Células TH1/metabolismo , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the diagnostic and therapeutic approach to gallstone ileus. MATERIAL AND METHODS: A gallstone ileus report, diagnosed by integrated radiological approach, treated by minilaparotomy plus enterolithotomy and followed up for two years. RESULTS: Traditional radiologic findings, ultrasonography and computed tomography showed both the stone in the bowel lumen and the cholecystoduodenal fistula with air in the biliary tract. The enterolithotomy alone worked out the obstruction and no complication was observed. DISCUSSION: Integrated radiologic examinations are indicated in defining nature, site and seriousness of gallstone ileus. In most cases surgical treatment is mandatory to work out both the bowel occlusion and bilioenteric illness even though it is often wiser to perform an operation of enterolithotomy alone owing to the general and local conditions of the patient. After this surgical approach, bilioenteric fistula disappears in most cases with no residual lithiasis; in the cases in which fistula and/or lithiasis persist, a decisive surgical operation can be performed in a second step.
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Colelitiasis/cirugía , Enfermedades del Íleon/cirugía , Obstrucción Intestinal/cirugía , Laparotomía/métodos , Fístula Biliar/diagnóstico , Fístula Biliar/etiología , Fístula Biliar/cirugía , Colelitiasis/complicaciones , Colelitiasis/diagnóstico , Enfermedad Crónica , Enfermedades Duodenales/diagnóstico , Enfermedades Duodenales/etiología , Enfermedades Duodenales/cirugía , Enfermedades de la Vesícula Biliar/diagnóstico , Enfermedades de la Vesícula Biliar/etiología , Enfermedades de la Vesícula Biliar/cirugía , Humanos , Enfermedades del Íleon/diagnóstico , Enfermedades del Íleon/etiología , Fístula Intestinal/diagnóstico , Fístula Intestinal/etiología , Fístula Intestinal/cirugía , Obstrucción Intestinal/diagnóstico , Obstrucción Intestinal/etiología , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
The aim of this prospective randomized study was to investigate anorectal manometric findings in hemorrhoid patients and to evaluate the clinical benefits and physiological consequences of additioning a lateral internal sphincterotomy (LIS) to haemorrhoidectomy. Anorectal manometry was preoperatively performed in forty-eight consecutive patients with prolapsed piles; resting and squeeze pressures, sphincter length and rectoanal inhibitory reflex were recorded. Ten healthy volunteers served as controls. Six patients were excluded because no raised and pressures were found. Forty-two patients were randomised: Group 1 (n = 22) patients underwent haemorrhoidectomy plus LIS; Group 2 (n = 20) patients underwent haemorrhoidectomy alone. Postoperative course was carefully evaluated; all patients were questioned about continence and anorectal manometry was repeated twice. Sphincter anomalies were found in 87.5% of patients. Haemorrhoidectomy alone did not affect anal pressures, which returned into the normal ranges after sphincterotomy. Postoperative course was better in LIS group. Anal stricture was seen in four patients without sphincterotomy; no patients with LIS experienced and incontinence. This study shows that high and pressures are very frequent in hemorrhoid patients; they are not due to hypertensive and cushions and might have a pathogenetic role. Anorectal manometry is very useful to identify patients with raised anal pressures; in these cases additioning a lateral internal sphincterotomy to haemorrhoidectomy seems justified; it significantly improves postoperative course and can be safely performed.
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Canal Anal/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Hemorroides/cirugía , Adulto , Canal Anal/fisiopatología , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Hemorroides/fisiopatología , Humanos , Masculino , Manometría/instrumentación , Manometría/métodos , Manometría/estadística & datos numéricos , Persona de Mediana Edad , Dolor Postoperatorio/diagnóstico , Estudios Prospectivos , Recto/fisiopatologíaRESUMEN
Laparoscopic cholecystectomy is associated with a significant risk of gallbladder perforations with bile and stone spillage. The retrieval of dropped stones is sometimes impossible, and intraperitoneally retained stones can be the source of serious complications, such as inflammatory masses or abscesses. The authors describe a patient in whom a large retroperitoneal abscess developed as a result of missed stone fragments during cholecystectomy. Although several cases of intraperitoneal abscess have been reported in the literature, retroperitoneal collection is very uncommon. Crushed and infected stones seem to be the essential prerequisite for abscess formation. Therefore, every attempt should be made to avoid stone spillage and intra-abdominally retained stones. Conversion to open surgery has to be considered in the presence of adverse factors, such as primary acute cholecystitis or cholecystitis induced by previous sphincterotomy, or bilirubinate stones believed to be infected. Abdominal abscess treatment requires removal of missed stones by surgical incision or new laparoscopic procedure because simple percutaneous drainage is usually unsuccessful.
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Absceso/etiología , Colecistectomía Laparoscópica/efectos adversos , Colelitiasis/cirugía , Infecciones por Escherichia coli/etiología , Infecciones por Pseudomonas/etiología , Espacio Retroperitoneal , Absceso/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Espacio Retroperitoneal/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To investigate anorectal manometric findings in patients with haemorrhoids and to evaluate the clinical effects and physiological consequences of adding a lateral internal sphincterotomy (LIS) to haemorrhoidectomy. DESIGN: Randomised prospective study. SETTING: Teaching hospital, Naples. PATIENTS: 48 consecutive patients with prolapsed piles who had anorectal manometry; 10 healthy volunteers served as controls. INTERVENTIONS: Resting and squeeze pressures, sphincter length and rectoanal inhibitory reflex were recorded. 6 patients were excluded because anal pressures were not raised, so 42 patients were randomised. 22 patients had haemorrhoidectomy plus LIS; and 20 had haemorrhoidectomy alone. MAIN OUTCOME MEASURES: Morbidity, continence, and anorectal manometry. RESULTS: Sphincter anomalies were found in 87.5% (n = 42) of patients. Haemorrhoidectomy alone did not affect anal pressures, which returned to the normal ranges after sphincterotomy. Those who had LIS did better postoperatively than those who had did not. 4 patients who did not have a sphincterotomy developed anal strictures. No patient who had LIS developed incontinence of faeces. CONCLUSIONS: High anal pressures are common in patients with haemorrhoids suggesting that they may have a pathogenetic role; anorectal manometry is useful in the investigation of anal pressure patterns; and when indicated, lateral sphincterotomy avoids pain, urinary retention, and stenosis, and is safe.
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Canal Anal/cirugía , Incontinencia Fecal/etiología , Hemorroides/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Femenino , Hemorroides/etiología , Humanos , Masculino , Manometría , Persona de Mediana Edad , Dolor Postoperatorio/etiología , Estudios ProspectivosRESUMEN
Interleukin (IL)-10 is a Th2 type pleiotropic cytokine that has been found to be produced at the tumor site and to be increased in sera of patients suffering from different types of cancer. IL-10 has been shown to hinder a number of immune functions, i.e., T lymphocyte proliferation, Th1 type cytokine production, antigen presentation, and lymphokine-activated killer cell cytotoxicity. To assess its prognostic value, we measured serum levels of IL-10 in 118 patients with advanced solid tumors before treatment, after completion of therapy, and during follow-up. Other prognostic variables, to which IL-10 results were compared, were analyzed as well. IL-10 serum levels were found significantly elevated in cancer patients with respect to healthy controls. Of interest, a significant decrease in IL-10 serum levels was observed in the responder group, whereas a significant increase was recorded in the non-responder group. Using univariate and multivariate analyses, a significant relationship was shown between IL-10 serum levels and both overall survival (OS) and time to treatment failure (TTF). Stepwise regression analysis selected IL-10 serum level, performance status (PS), and stage as the best association of variables with significant impact on OS and TTF. In conclusion, this study shows that IL-10 has an independent prognostic significance in patients with advanced solid tumors and may be useful for monitoring disease progression.
Asunto(s)
Biomarcadores de Tumor , Interleucina-10/sangre , Neoplasias/sangre , Adulto , Anciano , Citotoxicidad Inmunológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/mortalidad , Neoplasias/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Linfocitos T/inmunologíaRESUMEN
STUDY OBJECTIVE: To investigate the prognostic significance of interleukin (IL)-10 serum levels in advanced non-small cell lung cancer (NSCLC) patients. DESIGN: IL-10 serum levels were measured before chemotherapy, on completion of therapy, and at follow-up by means of a commercially available enzyme-linked immunoassay. The results were then analyzed in comparison with other prognostic variables, and a model predicting overall survival (OS) and time to treatment failure (TTF) was finally generated. SETTING: University hospital. PATIENTS: Sixty consecutive patients with TNM stage III or IV NSCLC undergoing conventional platinum-based regimens. RESULTS: Elevated levels of serum IL-10 were found in cancer patients with respect to healthy control subjects (17.7 +/- 4.4 vs 9.2 +/- 1.5 pg/mL, respectively; p < 0.05), with patients with metastatic disease showing significantly higher levels than patients with undisseminated cancer (21.0 +/- 4.2 vs 14.3 +/- 1.2 pg/mL, respectively; p < 0.05). Following completion of treatment, patients were classified as responders if they had achieved either one of the following: complete response, partial response, or stable disease; and nonresponders, in case of progressive disease. Retrospective analysis of basal IL-10 serum levels in these two subgroups showed a significant difference between responders and nonresponders (15.2 +/- 2.2 vs 21.4 +/- 4.2 pg/mL, respectively; p < 0.05). Moreover, a further significant increase in IL-10 serum levels was observed in nonresponders at the end of therapy (21.4 +/- 4.2 vs 26.0 +/- 4.3 pg/mL, prechemotherapy and postchemotherapy, respectively; p < 0.05), whereas values in responders were found to have significantly decreased (15.2 +/- 2.2 vs 14.8 +/- 2.2 pg/mL, prechemotherapy and postchemotherapy, respectively; p < 0.05). Using univariate and multivariate analyses, both OS and TTF were shown to be affected by the mean pathologic levels of IL-10. Stepwise regression analysis identified IL-10 serum level and stage as the prognostic factors related to OS, and IL-10 serum level and performance status as the prognostic factors related to TTF. CONCLUSIONS: In conclusion, this study shows that the measurement of pretreatment IL-10 serum levels is of independent prognostic utility in patients with NSCLC and may be useful for detection of disease progression.