Spontaneously ruptured hepatocellular carcinoma on non-cirrhotic liver: A prospective case series.

BACKGROUND AND AIMS: Spontaneous ruptured hepatocellular carcinoma is an uncommon complication, and there are scarce data about non-cirrhotic patients. Tumor treatment is not standardized and the risk of peritoneal dissemination is unclear. AIM: we analyzed the treatment and survival in patients with rHCC on non-cirrhotic liver. METHODS: One hundred and forty-one non-cirrhotic patients with hepatocellular carcinoma diagnosed by histology were included in a multicenter prospective registry (2018-2022). Seven of them (5%) presented with hemoperitoneum due to spontaneous rupture. RESULTS: Liver disease was associated in three patients (42.9%). A single nodule was detected in three cases (42.9%). One patient had vascular invasion and none extrahepatic spread. Initial hemostatic therapy and sequential treatment was individualized. Patients with single nodule were treated: resection (one case) with recurrence at 4 months treated with TACE and sorafenib. TACE/TAE followed by surgery (two cases) one in remission 43 months later, the other had liver recurrence at 18 months and was transplanted. Patients with multiple lesions were treated: TAE/emergency surgery and subsequent systemic therapy (two cases), one received lenvatinib (1-year survival) and the other sorafenib (5-month survival). TAE and surgery with subsequent systemic therapy (one case). Initial hemostatic surgery, dying on admission (one case). No patient developed intraperitoneal metastasis. All patients with multiple lesions died by tumor. The 3-year survival rate was 42.9%. CONCLUSIONS: Initial hemostasis was achieved in all patients by TAE/TACE or surgery. Subsequent treatment was individualized, based on tumor characteristics, regardless of rupture. Long-time remission could be achieved in single nodule patients.

Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study.

PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and liver-only disease ineligible for chemoembolization. PATIENTS AND METHODS: NASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS). RESULTS: 42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3-4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1). CONCLUSIONS: The combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT. TRIAL REGISTRATION NUMBER: NCT03380130.

Manejo de las hemorragias en el enfermo oncológico avanzado / Management of bleeding in the advanced oncologic patient

Hemorrhage in the advanced or terminal cáncer patient represents a distressing and complex situation in the palliative care setting, potentially leading to death of the patient due to massive loss of circulating volume. Although it is a relatively rare event, it is an urgent and distressing clinical problem for the patient, family and health care providers(1). Its incidence in patients with advanced cancer varies from 6% to 14% in solid tumors, being higher in head and neck cancers and up to 30% in hematological neoplasms[],[]. Among the risk factors are those related to the tumor, treatments, systemic factors, among others, and it may present as an acute catastrophic event, severe episodic bleeding or continuous low volume exudation[],[]. Available recom- mendations for the management of terminal hemorrhage are based on: identificaron of high-risk patients, early establishment of general supportive measures, local and systemic measures and the use of emergency or crisis medications[]. Treatment should be individualized, including interventions on the underlying causes and on the risk-benefit ratio of interventions for mitigation or control of bleeding, within the context of survival expectations. In the palliative patient at the end of life, decision making should be based on providing adequate symptomatic control, comfort measures and improving quality of life

La hemorragia en el paciente oncológico avanzado o también denominada terminal representa una situación angustiante y compleja en el ámbito de los cuidados paliativos, que potencialmente puede generar la muerte del paciente debido a la perdida masiva de volumen circulante. Aunque es un evento relativamente raro, es un problema clínico urgente y angustiante para el paciente, su familia y proveedores de salud[]. Su incidencia en pacientes con cáncer avanzado varia del 6% al 14%, en tumores sólidos, siendo más alta en canceres de cabeza y cuello y hasta el 30% en neoplasias hematológicas[],[]. Dentro de los factores de riesgo se encuentran aquellos relacionados con el tumor, los tratamientos, factores sistémicos entre otros, y puede presentarse como un evento catastrófico agudo, hemorragias episódicas graves o exudación continua de bajo volumen[],[]. Las recomendaciones disponibles para el manejo de la hemorragia terminal se basan en: la identificación de pacientes con alto riesgo, la instauración temprana de medidas generales de soporte, medidas locales y sistémicas y el uso de medicamentos de emergencia o crisis[]. El tratamiento debe ser individualizado, incluyendo las intervenciones en las causas subyacentes y en la relación riesgo-beneficio de las intervenciones para la mitigación o control de la hemorragia, dentro del contexto de las expectativas de la supervivencia. En el paciente paliativo al final de la vida la toma de decisiones debe tener como pilar: brindar un adecuado control sintomático, medidas de confort y mejorar la calidad de vida

Radiological response to nivolumab in patients with hepatocellular carcinoma: A multicenter analysis of real-life practice.

BACKGROUND AND AIMS: Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment. METHODS: We reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment. RESULTS: From the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00-10.92]; median overall survival was 12.82 months (95 %CI 10.92-34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions. CONCLUSION: Imaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challenging.

A Model Based on Noninvasive Markers Predicts Very Low Hepatocellular Carcinoma Risk After Viral Response in Hepatitis C Virus-Advanced Fibrosis.

BACKGROUND AND AIMS: Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS: This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS: A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.

FGFR4 increases EGFR oncogenic signaling in lung adenocarcinoma, and their combined inhibition is highly effective.

OBJECTIVES: Lung adenocarcinoma accounts for approximately half of lung cancer cases. Twenty to 50% of tumors of this type harbor mutations affecting epidermal growth factor receptor (EGFR) expression or activity, which can be therapeutically targeted. EGFR inhibitors in this context exhibit high efficacy and are currently used in the clinical setting. However, not all adenocarcinomas harboring EGFR mutations respond to therapy, so predictive biomarkers of therapeutic outcomes, as well as novel therapies sensitizing these tumors to EGFR inhibition, are needed. MATERIALS AND METHODS: We performed in vitro gene overexpression/silencing and tumorigenic surrogate assays, as well as in vitro and in vivo combination treatments with Fibroblast Growth Factor Receptor (FGFR)/EGFR inhibitors. At the clinical level, we determined FGFR4 expression levels in tumors from patients treated with EGFR inhibitors and correlated these with treatment response. RESULTS: We describe a cooperative interaction between EGFR and FGFR4, which results in their reciprocal activation with pro-oncogenic consequences in vitro and in vivo. This cooperation is independent of EGFR activating mutations and increases resistance to different EGFR inhibitors. At the therapeutic level, we provide evidence of the synergistic effects of the combination of EGFR and FGFR inhibitors in high FGFR4-expressing, EGFR-activated tumors in vitro and in vivo. Correlated with these results, we found that patients treated with EGFR inhibitors relapse earlier when their tumors exhibit high FGFR4 expression. CONCLUSIONS: We propose a novel predictive biomarker for EGFR-targeted therapy, and a highly efficacious combinatory therapeutic strategy to treat EGFR-dependent; this may may extend the use of appropriate inhibitors beyond EGFR-mutated adenocarcinoma patients.

FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy.

INTRODUCTION: There is substantial evidence for the oncogenic effects of fibroblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed specifically in lung adenocarcinoma. METHODS: We performed FGFR1 and EGFR overexpression and co-overexpression assays in adenocarcinoma and in inmortalized lung cell lines, and we also carried out surrogate and interaction assays. We performed monotherapy and combination EGFR/FGFR inhibitor sensitivity assays in vitro and in vivo in cell line- and patient-derived xenografts. We determined FGFR1 mRNA expression in a cohort of patients with anti-EGFR therapy-treated adenocarcinoma. RESULTS: We have reported a cooperative interaction between FGFR1 and EGFR in this context, resulting in increased EGFR activation and oncogenic signaling. We have provided in vitro and in vivo evidence indicating that FGFR1 expression increases tumorigenicity in cells with high EGFR activation in EGFR-mutated and EGFR wild-type models. At the clinical level, we have shown that high FGFR1 expression levels predict higher resistance to erlotinib or gefitinib in a cohort of patients with tyrosine kinase inhibitor-treated EGFR-mutated and EGFR wild-type lung adenocarcinoma. Dual EGFR and FGFR inhibition in FGFR1-overexpressing, EGFR-activated models shows synergistic effects on tumor growth in vitro and in cell line- and patient-derived xenografts, suggesting that patients with tumors bearing these characteristics may benefit from combined EGFR/FGFR inhibition. CONCLUSION: These results support the extended the use of EGFR inhibitors beyond monotherapy in the EGFR-mutated adenocarcinoma setting in combination with FGFR inhibitors for selected patients with increased FGFR1 overexpression and EGFR activation.

Fiebre de origen oscuro como manifestación de lupus eritematoso sistémico / Fever of unknown origin as manifestation of systemic lupus erythematosus

Resumen: La fiebre de origen oscuro se caracteriza por un espectro clínico de pacientes que consultan por padecer fiebre como manifestación única o predominante, mayor o igual a 38.3ºC, de más de tres semanas de evolución y en quienes los resultados de la evaluación clínica y estudios paraclínicos iniciales no han identificado su causa. Se han agrupado cinco categorías que engloban las causas de la fiebre de origen oscuro, entre las que se encuentran las enfermedades infecciosas, neoplásicas, inflamatorias no infecciosas, misceláneas y de origen desconocido. El lupus eritematoso sistémico es una enfermedad de tipo autoinmunitario que afecta el tejido conectivo y tiene amplio rango de manifestaciones clínicas, entre las que destacan al inicio poliartritis, úlceras mucocutáneas y el eritema malar; el lupus eritematoso sistémico es una de las causas inflamatorias no infecciosas de fiebre de origen oscuro. Se comunica el caso clínico de una paciente de 51 años de edad, quien consultó al servicio de Medicina interna, por padecer un cuadro clínico de 30 días de evolución, con fiebre intermitente, diaria y cuantificada entre 38.5 y 39°C, asociada con pérdida significativa de peso; en quien se diagnosticó por hallazgos clínicos y paraclínicos lupus eritematoso sistémico, fue tratada con hidroxicloroquina y prednisolona, con desaparición de la fiebre y mejoría del estado general.

Abstract: Fever of unknown origin is defined as a clinical spectrum of patients who consulted for presenting fever as a single or predominant manifestation, greater or equal to 38.3ºC, more than 3 weeks of evolution, and in whom clinical evaluation results and initial paraclinical studies have not identified its cause. Five categories group the causes of fever of unknown origin which include infectious, neoplastic, inflammatory non-infectious, miscellaneous and of unknown origin. Systemic lupus erythematosus is an autoimmune disease that affects connective tissue and has a wide range of clinical manifestations, among which the presence of polyarthritis, mucocutaneous ulcers and malar erythema stand out at the beginning; systemic lupus erythematosus is one of the non-infectious inflammatory causes of fever of unknown origin. A clinical case report is made, of a 51-year-old woman, who consulted to Internal Medicine, with a clinical picture of 30 days of evolution, with intermittent fever, daily and quantified between 38.5 and 39ºC, associated with significant weight loss; to which it was diagnosed by clinical and paraclinical findings systemic lupus erythematosus, treated with hydroxychloroquine and prednisolone, achieving disappearance of the fever and improvement of the general state of the patient.

The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction.

The FGFR4-388Arg variant has been related to poor prognosis in several types of cancer, including lung cancer. The mechanism underlying this association has not been addressed in detail in patients with this pathology. Here, we report that this FGFR4 variant induces MAPK and STAT3 activation and causes pro-oncogenic effects in NSCLC in vitro and in vivo. This variant induces the expression of EMT-related genes, such as N-cadherin, vimentin, Snail1 and Twist1. Indeed, the induction of N-cadherin protein expression by this variant is essential for its pro-tumorigenic role. The presence of the FGFR4-388Arg variant correlates with higher N-cadherin expression levels in clinical NSCLC samples and with poorer outcome in patients with FGFR expression. These results support the prognostic role of this FGFR variant in lung cancer and show that these effects may be mediated by the induction of N-cadherin expression and an EMT phenotype.

Orthodontic fixed retainers: a systematic review / Retenedores fijos en ortodoncia: revisión sistemática

ABSTRACT Introduction: the objective of this study was to evaluate the periodontal effects of fixed retainers in the long term. Methods: a search in electronic databases (PubMed, Cochrane Library, Science Direct, Embase, ProQuest, Ebsco, Biomed Central, Medline, Lilacs, and Google Scholar) and a manual search with no language restrictions. The inclusion criteria were: randomized clinical trials and meta-analysis, prospective and retrospective studies, studies in humans, clinical and radiographical studies evaluating the periodontium, performed during the 1987-2014 period, up to 10 years of follow-up. Four authors extracted data from the selected studies independently. Results: after applying the inclusion criteria, we selected 4 studies in which a total of 405 patients were evaluated. All the studies were longitudinal and retrospective. There was a greater prevalence of gingival recessions, especially in mandibular incisors, which are more vulnerable. There were no significant changes in terms of alveolar bone index or calculus index. The survival rate of fixed retainers was 50% or higher. Due to the heterogeneity of the selected studies, including difference in study population, differences in methods to assess the intervention, and follow-up periods, it was impossible to quantify the variables to perform a meta-analysis. Conclusions: the selected studies had a middle level of evidence. The greatest gingival recessions occurred with the use of fixed retainers in a long time; however, there is no alteration of the alveolar bone level. The studies recommend encouraging patients to maintain good oral hygiene. The findings of this review should be cautiously taken due to the resulting level of evidence, and the general recommendation for clinicians is that, in the long run, these retainers appear to be safe to maintain the alignment of mandibular incisors, although more studies with greater scientific rigor are required. There were no conflicts of interest and this study did not have any kind of financial support.

RESUMEN. Introducción: el objetivo del presente estudio consistió en evaluar los efectos periodontales de los retenedores fijos a largo plazo. Métodos: se realizó una búsqueda en bases de datos electrónicas (PubMed, Cochrane Library, Science Direct, Embase, ProQuest, Ebsco, Biomed Central, Medline, Lilacs y Google Scholar) y una búsqueda manual sin restricción de lenguaje. Los criterios de inclusión fueron: ensayos clínicos aleatorizados y metaanálisis, estudios prospectivos y retrospectivos, estudios en humanos, estudios en los que se evaluara clínica y radiográficamente el periodonto, periodo comprendido entre 1987 y 2014, seguimiento hasta 10 años. Cuatro autores extrajeron independientemente los datos de los estudios seleccionados. Resultados: después de aplicar los criterios de inclusión, se seleccionaron 4 estudios en los que se evaluaron un total de 405 pacientes. Todos los estudios fueron longitudinales retrospectivos. Se encontró una mayor prevalencia de recesiones gingivales, especialmente de los incisivos mandibulares, que son más vulnerables. No mostraron cambios significativos ni el índice de hueso alveolar ni el índice de cálculo. La tasa de supervivencia de los retenedores fijos fue mayor del 50%. Debido a la heterogeneidad de los estudios seleccionados, entre los cuales se encuentra la diferencia en la población de estudio, diferencias en los métodos para evaluar la intervención y el tiempo de seguimiento, fue imposible cuantificar las variables para realizar un metaanálisis. Conclusiones: los estudios seleccionados tuvieron un nivel de evidencia medio. Se presentan mayores recesiones gingivales con el uso de los retenedores fijos a largo plazo; sin embargo, no hay alteración del nivel óseo alveolar. Los estudios recomiendan incentivar al paciente para que mantenga una buena higiene oral. Los resultados de esta revisión se deben tomar con cautela por el nivel de evidencia que arrojaron, y la recomendación general para el clínico es que, a largo plazo, estos retenedores parecen ser seguros para mantener el alineamiento de incisivos mandibulares, aunque se requieren más estudios con mayor rigor científico. No hubo conflictos de intereses y la investigación no contó con ningún tipo de financiamiento.

Effects of shiga toxin 2 on cellular regeneration mechanisms in primary and three-dimensional cultures of human renal tubular epithelial cells.

Shiga toxin (Stx)-producing Escherichia coli (STEC) causes post-diarrheal Hemolytic Uremic Syndrome (HUS), which is one of the most common causes of acute renal failure in children in Argentine. The aim of the present work was to study the effects of Shiga toxin type 2 (Stx2) on regenerative mechanisms of primary cultures of human cortical renal tubular epithelial cells (HRTEC) and three-dimensional (3D) cultures of HRTEC. Primary cultures of HRTEC were able to develop tubular structures when grown in matrigel, which showed epithelial cells surrounding a central lumen resembling the original renal tubules. Exposure to Stx2 inhibited tubulogenesis in 3D-HRTEC cultures. Moreover, a significant increase in apoptosis, and decrease in cell proliferation was observed in tubular structures of 3D-HRTEC exposed to Stx2. A significant reduction in cell migration and vimentin expression levels was observed in HRTEC primary cultures exposed to Stx2, demonstrating that the holotoxin affected HRTEC dedifferentiation. Furthermore, a decreased number of cells expressing CD133 progenitor marker was found in HRTEC cultures treated with Stx2. The CD133 positive cells also expressed the Stx receptor globotriaosylceramide, which may explain their sensitivity to Stx2. In conclusion, Stx2 affects the regenerative processes of human renal tubular epithelial cells in vitro, by inhibiting cell dedifferentiation mechanisms, as well as tubules restoration. The development of 3D-HRTEC cultures that resemble original human renal proximal tubules is a novel in vitro model to study renal epithelial repair mechanisms after injury.

Effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on primary cultures of human renal tubular epithelial cells.

Shiga toxin (Stx)-producing Escherichia coli (STEC) cause post-diarrhea Hemolytic Uremic Syndrome (HUS), which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB) that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC) and compare its effects with those produced by Shiga toxin type 2 (Stx2), in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2.

How to Attain an Ultralow Interfacial Tension and a Three-Phase Behavior with a Surfactant Formulation for Enhanced Oil Recovery: A Review. Part 2. Performance Improvement Trends from Winsor's Premise to Currently Proposed Inter- and Intra-Molecular Mixtures.

The minimum interfacial tension occurrence along a formulation scan at the so-called optimum formulation is discussed to be related to the interfacial curvature. The attained minimum tension is inversely proportional to the domain size of the bicontinuous microemulsion and to the interfacial layer rigidity, but no accurate prediction is available. The data from a very simple ternary system made of pure products accurately follows the correlation for optimum formulation, and exhibit a linear relationship between the performance index as the logarithm of the minimum tension at optimum, and the formulation variables. This relation is probably too simple when the number of variables is increased as in practical cases. The review of published data for more realistic systems proposed for enhanced oil recovery over the past 30 years indicates a general guidelines following Winsor's basic studies concerning the surfactant-oil-water interfacial interactions. It is well known that the major performance benefits are achieved by blending amphiphilic species at the interface as intermolecular or intramolecular mixtures, sometimes in extremely complex formulations. The complexity is such that a good knowledge of the possible trends and an experienced practical know-how to avoid trial and error are important for the practitioner in enhanced oil recovery.

Apparent equilibration time required for surfactant-oil-water systems to emulsify into the morphology imposed by the formulation. Part 2: Effect of sec-butanol concentration and initial location.

Winsor type I equilibrated surfactant-oil-water (SOW) systems produce o/w emulsions upon stirring. However, if the surfactant is initially dissolved in the oil phase, the attained type after inmediate emulsification is usually w/o. If the SOW system is partially equilibrated, it could result in a normal o/w emulsion, as if it were fully equilibrated. The minimum contact time for that to happen, the so-called apparent equilibration time tAPE, was previously shown (Langmuir 2002, 18, 607) to strongly depend on formulation, surfactant molecular weight, and oil viscosity. The present report shows that it depends on alcohol concentration and location in the unequilibrated system.