The European contribution to "Sugarbaker's protocol" for the treatment of colorectal peritoneal carcinomatosis.

INTRODUCTION: In 1981, Dr. PH Sugarbaker, challenging oncological orthodoxy, considered carcinomatosis to be a locoregional stage of the disease that was still susceptible to treatment with curative intent. To this end he developed a new therapeutic alternative based on the combined treatment. The macroscopic disease treated by maximum radical oncological cytoreductive surgery (through the peritonectomies described by him), followed by treatment of the residual microscopic disease with the direct intra-abdominal application of intraoperative chemotherapy with locoregional intensification, modulated by hyperthermia and early normothermic postoperative intra-abdominal chemotherapy. Using this new therapeutic regimen, known as "Sugarbaker s Protocol", his group has reported 45% survival rates in carcinomatosis of colorectal origin at 5 years, and, in selected groups of patients, 50% survival rates at 5 years. The scientific community, however, has criticized these results considering that: it is a personal experience, with a not homogenous treatment protocol with developmental modifications over time, that it is a retrospective non-randomized study, and finally that the cytostatics used in his protocol are obsolete. Various European groups have replied to these main criticisms confirming the good results that this new therapeutic alternative offers for patients with carcinomatosis of colorectal origin. The purpose of this article is to present these contributions. MATERIAL AND METHODS: All the articles published in the English language by European groups in the world s medical literature have been reviewed using the Pubmed-MEDLINE database to identify the relevant articles related to the treatment of carcinomatosis of colorectal origin using cytoreduction and intraperitoneal chemotherapy from January 1980 to January 2008. RESULTS: The European contribution during these 25 years in favour of the "Sugarbaker s Protocol" has consisted fundamentally in: a) one multicenter retrospective study; b) two randomized prospective phase III studies; and c) the use of oxaliplatin and irinotecan as new cytostatic agents in the protocols for intraperitoneal chemotherapy. At the same time, two new transcendental European contributions have been made in which the possibility has been considered of combined simultaneous treatment for patients with hepatic metastases and carcinomatosis, and the introduction, as a selection factor, of patients responsive to intravenous induction chemotherapy within the regimen of sandwich treatment (with systemic neoadjuvant and adjuvant chemotherapy) complementary to intraperitoneal chemotherapy. CONCLUSIONS: The results obtained by European groups using "Sugarbaker s protocol" and "Elias protocol" with oxaliplatin compel us to request that these treatments be considered by all professionals involved in the treatment of patients with colorectal carcinomatosis as the best treatment currently available for this condition. Furthermore a randomized, prospective, multicenter study should be carried out to clarify its value and the degree of scientific evidence. A validation of this treatment will change, in the future, the dogmatic consideration of carcinomatosis as an incurable disease stage.

[Prevalence and treatment of oncologic disease in the elderly --an impeding challenge]. / Prevalencia y tratamiento de la patología oncológica en el anciano. El reto que se avecina.

Life expectancy in Spain has more than duplicated during the last 20th Century, and is currently 75 years for men and 83 years for women. Predictions on the evolution of the National and global population anticipate a demographic shock in Spain when individuals older than 65 years eventually make up more than 33.5% of the Spanish population by year 2050. It is known that cancer is directly related with age, and that it is a disease of older people -at least 60% of all cancers are diagnosed in patients older than 65 years. The older people group is the most important group of patients in oncologic practice today. Predictions on the aging of the Spanish population show that cancer in the aging patient and its treatment must be considered a first-line health problem. The diagnosis of cancer is not associated with death in the majority of patients. Sixty percent of cancers are globally cured or chronified. This advanced prognosis has its toll not only in the expectancy of treatment but also in subsequent follow-up and post-treatment adverse effects that can be generated. A greater and better knowledge and understanding of the aging process will allow to identify and select those old patients that can benefit from prevention and treatment options, and more importantly will identify those other patients that are not candidates to treatments with curative intention because of their frail status. Progress in surgery, mainly in minimally invasive surgery, and its application to the field of oncologic surgery allows to forecast that a greater number of aging patients will benefit from treatment with curative intent. Age will not be a barrier for adequate treatment in healthy elderly patients, especially in those with long life expectancy and functional reserves. Fighting this healthcare discrimination is one of the main priorities in the strategy of improved health in the elderly. We present in this study and analyze the foreseen changes in the world s population, particularly in Spain; the association between cancer and age with its peculiar specificities; the general criteria for frailty in older patients, the limitations that aging generate for adjuvant treatments, and the new alternatives of treatment to be used in elderly oncologic patients for the most frequent tumors.

[Reversible alterations in the dentate nuclei and rapid-onset cerebral atrophy due to neurotoxicity caused by lithium]. / Alteraciones reversibles en los nucleos dentados y atrofia cerebral de rapida instauracion debido a neurotoxicidad por litio.

INTRODUCTION: Treatment with lithium can cause several neurological side effects, even at therapeutic levels. CASE REPORT: We report the case of a 49-year-old woman, with bipolar disorder and depression, undergoing treatment with lithium, antidepressants and antipsychotics, who was admitted to hospital due to a clinical picture of visual hallucinations with an elevated lithaemia of 2.1 mEq/L (therapeutic range: 0.6-1.2 mEq/L). The patient developed a severe encephalopathy that required the use of assisted ventilation in the intensive care unit. Initial magnetic resonance imaging showed a reversible bilateral symmetrical hyperintensity in the dentate nuclei in T2 and T2-FLAIR sequences. Over the following months she gradually developed a pancerebellar syndrome with evidence of a marked loss of bilateral volume in the cerebellum, above all at the expense of the vermis, which was accompanied by a permanent and disabling cerebellar syndrome. CONCLUSIONS: Although treatment with lithium can cause a variety of neurological side effects, they are usually reversible. However, they occasionally give rise to permanent and disabling sequelae, as in the case of the patient reported here, with a marked and progressive cerebellar atrophy, accompanied by permanent sequelae in the form of a disabling cerebellar syndrome. The cerebellar neurotoxicity of lithium must be taken into account in the broad differential diagnosis of cerebellar ataxia in adults.

TITLE: Alteraciones reversibles en los nucleos dentados y atrofia cerebral de rapida instauracion debido a neurotoxicidad por litio.Introduccion. El tratamiento con litio puede ocasionar diversos efectos adversos neurologicos, incluso con niveles terapeuticos. Caso clinico. Mujer de 49 años, con trastorno bipolar y depresion, en tratamiento con litio, antidepresivos y antipsicoticos, que ingreso por un cuadro de alucinaciones visuales con una litemia elevada de 2,1 mEq/L (rango terapeutico: 0,6-1,2 mEq/L). Progreso a una encefalopatia grave que requirio asistencia respiratoria en la unidad de cuidados intensivos. La resonancia magnetica cerebral inicial mostro una hiperintensidad simetrica bilateral reversible en los nucleos dentados en las secuencias T2 y T2-FLAIR. A lo largo de los meses posteriores desarrollo de forma progresiva un sindrome pancerebeloso con evidencia de una marcada perdida de volumen bilateral en el cerebelo, sobre todo a expensas del vermis, que se acompaño clinicamente de un sindrome cerebeloso permanente e invalidante. Conclusiones. Aunque el tratamiento con litio ocasiona efectos adversos neurologicos variados, estos suelen ser reversibles. Puede dar lugar a secuelas permanentes e incapacitantes, como la paciente descrita, con una atrofia cerebelosa marcada y progresiva, acompañada de secuelas permanentes en forma de sindrome cerebeloso invalidante. La neurotoxicidad cerebelosa del litio debe considerarse en el amplio diagnostico diferencial que representa la ataxia cerebelosa del adulto.

The effect of partial substitution of Ni by Mg on the structural, magnetic and spectroscopic properties of the double perovskite Sr2NiTeO6.

In this report, the structural, magnetic and spectroscopic properties of the freeze-drying synthesized Sr2Ni1-xMgxTeO6 (x = 0.0, 0.1, 0.2, 0.3 and 0.5) oxides are analyzed by means of X-ray powder diffraction (XRPD) and neutron powder diffraction (NPD), electron paramagnetic resonance, diffuse reflectance and magnetic susceptibility. The XRPD and NPD data analysis using the mode-crystallography approach have revealed that at room temperature (RT), all the compositions are monoclinically distorted with the space group I2/m. The high and low temperature analyses have shown that these materials suffer a series of three structural phase transitions. The EPR results have shown that the spectra of all the compositions are centred at g≈ 2.28, indicating a slightly distorted octahedral environment of Ni(2+), which is in agreement with the crystal structure analysis. The increase of the Mg(2+) content in Sr2Ni1-xMgxTeO6, provokes a decrease of the dipolar interaction effects and thus, the resonance becomes narrower. This resonance does not completely disappear which leads to the idea that the long-range magnetic order is not completely established when x≥ 0.3. The substitution of the Ni(2+) (S = 1) ions by Mg(2+) (S = 0) ions, also induces a weakening of the antiferromagnetic interactions, which is reflected in the diminishing of the absolute value of θ and the Néel temperature TN. The magnetic structure determination revealed the existence of an antiferromagnetic coupling for x- and z-spin components of the nickel atoms.

Peritoneal carcinomatosis of colorectal origin. Current treatment. Review and update.

Colorectal cancer is the most frequent tumor of the digestive tract. The high incidence of abdominal dissemination; the poor prognosis of these patients, with median survival consistently ranging from 5 to 9 months in all studies of peritoneal carcinomatosis from colorectal cancer; the failure of adjuvant systemic chemotherapy treatment with a maximal survival of 18 months despite the development of new cytostatic drugs, and new combinations of use, make it crucial to search for and develop new treatment strategies. We review the principles of Sugarbaker s treatment protocol, which involves the combination of maximum cytoreductive radical oncological surgery for the treatment of all macroscopically disseminated disease with maximum perioperative intraperitoneal intensification chemotherapy to treat residual microscopic disease. We present the results of several scientific papers, all of them phase II studies with more than 10 patients treated, published in the medical literature by the main groups working in this line of treatment, together with the only phase III study reported and published so far, and finally the results of a recently reported retrospective international multicenter study. With this new alternative therapeutic approach, overall mean survival is 40% at 36 months, and 20% at 5 years. Based on these results, this new therapeutic approach is proposed as the treatment of choice for these unfortunate patients.

Synthesis, structural, magnetic and phase-transition studies of the ferromagnetic La2CoMnO6 double perovskite by symmetry-adapted modes.

A powdered La2CoMnO6 double perovskite was synthesized by the solid-state reaction method, and its crystal structure was investigated by (mode-crystallography) Rietveld analysis using X-ray and neutron powder diffraction data. La2CoMnO6 material is a monoclinic perovskite at room temperature, adopting the space group P21/n (a(-)a(-)b(+)), , c ≈ 2ap and Z = 2. The P21/n phase can be described effectively by three distortion modes (GM4(+), X3(+), X5(+)) of the Fm3[combining macron]m (a(0)a(0)a(0)) parent phase. The comparative study of the material and those in the Ln2CoMnO6 and Ln2NiMnO6 families has shown a general trend in nearly all the materials, has served to select a common direction in the sub-space spanned by X5(+), tri-linearly coupled to the order parameters of the cubic to monoclinic first order phase transition. This direction has been used to parametrize the refinements and to perform reliable refinements in the high-temperature intermediate distorted trigonal phase, R3[combining macron] (a(-)a(-)a(-)), for which only one effectively acting irrep has been deduced: GM5(+), physically a tilt of the oxygen sharing octahedra of Co and Mn. Its temperature evolution up to the prototype cubic phase has been fitted in the framework of the Landau Theory of Phase Transitions, showing a behavior typical of a tricritical point. The low-temperature neutron powder diffraction data have served to solve the magnetic structure: three indistinguishable ferromagnetic models with the space groups P21/n and P2/n' are proposed.

Structural phase transitions and magnetic and spectroscopic properties of the double perovskites Sr2Co1-xMgxTeO6 (x = 0.1, 0.2 and 0.5).

The structural and magnetic properties of a series of ordered double perovskites with the formula Sr(2)Co(1-x)Mg(x)TeO(6) (x = 0.1, 0.2 and 0.5) are investigated by X-ray diffraction, low temperature neutron diffraction, electron paramagnetic resonance and magnetic susceptibility. The progressive substitution of the paramagnetic Co(2+) high spin ion by the diamagnetic Mg(2+), of about the same size, induces changes in the room temperature crystal structure, from a distorted P2(1)/n phase for the undoped Sr(2)CoTeO(6) oxide to the I4/m of the end member (Sr(2)MgTeO(6)). These perovskites experience structural transitions on heating, the temperature at which the transitions occur being smaller as x increases. The novel approach of mode-crystallography is used for the analysis. All oxides show antiferromagnetic exchange interactions between Co(2+) ions but the long range antiferromagnetic order is not achieved for the phase with x = 0.5. The low temperature neutron diffraction data have been evaluated using a full symmetry analysis. Results are consistent with an unquenched orbital contribution of a high spin Co(2+) ion.

Effects of triflusal in patients with prosthetic heart valves.

The biological effects of a new antiplatelet agent, triflusal, were evaluated in patients with cardiac valvular prostheses. Each patient received 900 mg/day of oral triflusal for 30 days. Triflusal significantly inhibited platelet aggregation induced by adenosine diphosphate (1 to 5 mumol) or epinephrine (12.5 mumol), showing a slight effect on bleeding time (basal: 6 +/- 1.7 min; 30 days of treatment: 8.0 +/- 2.7 min). Serum levels of thromboxane B2 were significantly reduced during treatment, but changes in serum levels of 6-keto-prostaglandin F1 alpha were not observed, suggesting that triflusal does not affect prostacyclin biosynthesis by the vascular wall. The results show that triflusal has a marked inhibitory and selective effect on platelet function in patients with cardiac valvular prostheses.

[Spinal cord hemorrhage complicating diagnostic lumbar puncture]. / Complicación espinal hemorrágica secundaria a una punción lumbar diagnóstica.

INTRODUCTION: Spinal cord hematoma is a serious and feared complication of lumbar puncture. We here describe two patients who developed a spinal cord hematoma following diagnostic lumbar punctures. CASE REPORTS: CASE 1: a 22-year-old male with a syndrome of cerebrospinal fluid hypotension, with normal coagulation parameters, underwent a traumatic, diagnostic lumbar puncture followed, a few hours later, by back pain irradiated to the legs. MRI showed the presence of a subdural hematoma from the lower dorsal region to the sacral region. A conservative approach, without surgery, was decided and he showed a complete recovery. CASE 2: a 69-year-old woman underwent a diagnostic lumbar puncture for the study of recent-onset headache with tinnitus and unstable gait. Puncture was traumatic and cerebrospinal fluid was normal. A few hours later, she complained of back pain and sciatica, and examination revealed a bilateral Lassegue sign. She required urinary catheterization. MRI showed an epidural hematoma from the T10 vertebra to the sacral area. Her outcome with a conservative approach was also excellent. CONCLUSIONS: Spinal cord hematomas can occur after a traumatic lumbar puncture in people without coagulation disorders or any other predisposing factor. Although surgery has been traditionally advocated in these cases, a conservative approach is an option when symptoms are mild and a close follow-up is possible.

[Incidence of lymphoid neoplasms in patients with HIV infection]. / Incidencia de neoplasias linfoides en pacientes con infección por el HIV.

BACKGROUND: The incidence, histologic type and clinical characteristics of the lymphoid neoplasms found in patients with HIV infection may be influenced by environmental factors. These characteristics were herewith investigated in the authors medium. METHODS: The medical records of the patients in whom lymphoma was diagnosed were reviewed studying the usual clinical, epidemiological, histological and biological variables. RESULTS: Fourteen patients: 10 with non Hodgkin lymphomas and four with Hodgkin disease were studied. The prevalence was 5% of the total number of patients with AIDS. Seven patients of the former and none of the latter had previously uncomplicated HIV infection. The following histologic types were observed: two Burkitt lymphoma, 4 undifferentiated lymphomas and 4 immunoblastic lymphomas among the non Hodgkin cases and two with mixed cellularity, one lymphocytic depletion and one undetermined among the Hodgkin's cases. Eighty percent of the patients with non Hodgkin lymphoma and 50% of the patients with Hodgkin disease presented a IV-B stage. The median of survival was 2.5 months (limits 1-8) for non Hodgkin cases and 11 months (limits 1-36) for the patients with Hodgkin disease. CONCLUSIONS: The prevalence of lymphoma in patients with AIDS in the authors' medium is similar to that referred in other studies although a high proportion of Hodgkin's disease may be found.