FDG PET/CT in colorectal cancer. / FDG PET/TC en el cáncer colorrectal.

Colorectal cancer is the third most frequent cancer worldwide. Although its incidence is increasing, mainly in those aged under50, mortality has decreased by 50% in the more developed countries, principally due to the adoption of new practices in prevention, diagnosis and treatment. In particular, the various diagnostic imaging modalities allow improved therapeutic decision-making, evaluation of the response and early detection of recurrence. The aim of this paper is to review the available scientific evidence on the value of positron emission tomography with 18F-FDG (18F-FDG PET/CT) in the colorectal cancer, with special emphasis on the indications of the guidelines and recommendations of the main international scientific associations regarding this imaging technique.

Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) vs choline-positron emission tomography-computed tomography (choline-PET/CT) for selecting treatments in recurrent prostate cancer.

OBJECTIVE: To determine the effectiveness of whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) in detecting metastases by comparing the results with those from choline-positron emission tomography-computed tomography (choline-PET/CT) in patients with biochemical relapse after primary treatment, and no metastases in bone scintigraphy, CT and/or pelvic MRI, or metastatic/oligometastatic prostate cancer (PCa). Patients with this disease profile who could benefit from treatment with stereotactic body radiation therapy (SBRT) were selected and their responses to these techniques were rated. MATERIALS AND METHODS: This was a prospective, controlled, unicentric study, involving 46 consecutive patients from our centre who presented biochemical relapse after adjuvant, salvage or radical treatment with external beam radiotherapy, or brachytherapy. After initial tests (bone scintigraphy, CT, pelvic MRI), 35 patients with oligometastases or without them were selected. 11 patients with multiple metastases were excluded from the study. WB-DW-MRI and choline-PET/CT was then performed on each patient within 1 week. The results were interpreted by specialists in nuclear medicine and MRI. If they were candidates for treatment with ablative SBRT (SABR), they were then evaluated every three months with both tests. RESULTS: Choline-PET/CT detected lesions in 16 patients that were not observable using WB-DW-MRI. The results were consistent in seven patients and in three cases, a lesion was observed using WB-DW-MRI that was not detected with choline-PET/CT. The Kappa value obtained was 0.133 (p = 0.089); the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB-DW-MRI were estimated at 44.93, 64.29, 86.11, and 19.15%, respectively. For choline-PET/CT patients, the sensitivity, specificity, PPV, and NPV were 97.10, 58.33, 93.06, and 77.78%, respectively. CONCLUSIONS: Choline-PET/CT has a high global sensitivity while WB-DW-MRI has a high specificity, and so they are complementary techniques. Future studies with more enrolled patients and a longer follow-up period will be required to confirm these data. The initial data show that the best technique for evaluating response after SBRT is choline-PET/CT. Trial registration number NCT02858128.

Biotinylated m4-toxin demonstrates more M4 muscarinic receptor protein on direct than indirect striatal projection neurons.

The striatum has nearly equal numbers of striatonigral and striatopallidal projection neurons. All are GABAergic and inhibitory, but they lie in separate neuronal circuits ('direct' and 'indirect', respectively) that appear to exert opposite effects on movement. Methods are needed to evaluate the function of each circuit. A potential way to control striatonigral neurons selectively is via M4 muscarinic receptors. The striatum has many more M4 receptors than other tissues, they are located on approximately half of all projection neurons, and mRNA for M4 receptors is prevalent only in striatonigral neurons. In order to more rigorously compare the distribution of M4 receptors on rat neurons in these pathways a toxin that binds with very high specificity to M4 receptors (m4-toxin) was biotinylated for use as a selective probe for M4 receptor protein. Pooled biotin-toxin complexes were found to retain high M4-specificity and affinity. Neurons were first labeled by retrograde transport of fluorescent microbeads (FluoSpheres) injected into the substantia nigra and globus pallidus. Coincident labeling of only 4% of the cells confirmed the validity of the retrograde labeling technique. Labeled neurons were probed for M4 receptor protein using biotinylated m4-toxin and fluorescent avidin. M4 receptors were found on 14% of indirect and 86% of direct neurons. It may be concluded that there is a relative abundance of M4 receptors controlling the direct pathway. This work supports the hypothesis that M4-selective drugs will prove useful to control the function of striatonigral neurons in the direct projection pathway.

Anti-muscarinic toxins from Dendroaspis angusticeps.

Toxins from the venom of the African green mamba, Dendroaspis angusticeps, fulfill a major need for selective ligands for some of the five genetically defined subtypes of muscarinic acetylcholine receptors (m1-m5). Two toxins have been found that are highly selective antagonists for m1 and m4 receptors (m1-toxin and m4-toxin, respectively). Two other toxins (MT1 and MT2) bind with high affinity to both m1 and m4 receptors, and are agonists. Components of the venom also modify the binding of radiolabeled antagonists to m2 receptors, but an m2-selective toxin has not yet been isolated, m1-Toxin can bind to m1 receptors at the same time as typical competitive antagonists, suggesting that this toxin binds to the N-terminal and outer loops of m1 receptor molecules, rather than within the receptor pocket where typical agonists and antagonists bind. The binding of toxins to the outer parts of receptor molecules probably accounts for their much higher specificity for individual receptor subtypes than is seen with smaller ligands. Toxins are useful for identifying, counting, localizing, activating and blocking m1 and m4 receptors with high specificity.

[Upper digestive hemorrhage caused by ulcerated periampullary leiomyoma]. / Hemorragia digestiva alta por un leiomioma periampular ulcerado.

Duodenal leiomyoma represents a very unusual cause for acute gastrointestinal bleeding. The authors report the case of a 49-year-old male with a massive bleeding from an ulcerated duodenal leiomyoma involving the ampulla of Vater. An emergency Whipple's pancreaticoduodenectomy was carried out under suspicion of local malignancy. It is emphasized that the proper diagnosis of smooth muscle tumors is often difficult, both clinically and from the pathological point of view.

[Disseminated encephalic cryptococcosis as a form of presentation of idiopathic T-CD4 lymphocytopenia]. / Criptococosis encefálica diseminada como forma de presentación de una linfocitopenia T-CD4 idiopática.

INTRODUCTION: The term idiopathic T-CD4 lymphocytopenia is used to describe a new syndrome, defined as reduced T-CD4 lymphocytes in persons with no evidence of HIV infection or other causes which would explain the immunosuppression (secondary to neoplasties, immunosuppressive treatment, hereditary immunodeficiencies, infections, etc.). The reduced number of T-CD4 lymphocytes leads to deterioration in cellular immunity and therefore this leads to a predisposition to develop tumors and opportunist infections in patients with such defects. CLINICAL CASE: We describe a case of depletion of T-CD4 lymphocytes, associated with disseminated encephalic cryptococcosis (multiple cortical, capsulo-ganglionar, thalamic and cerebellar cryptococcomas) in a patient with no evidence of HIV infection. The case we present fulfilled diagnostic criteria for idiopathic T-CD4 lymphocytopenia, a clinical condition seldom described in this country. We discuss the pathogenic mechanisms of cryptococcosis, the different varieties of Cryptococcus neoformans and their different roles as the cause of opportunist infections in humans. CONCLUSIONS: In view of the neurotrophism of this fungus, the neurological signs and symptoms should make one suspect the presence of Cryptococcus neoformans infection in non-HIV carriers with cellular immunity defects such as those present in idiopathic T-CD4 lymphocytopenia.

Whether to determine HER2 status for breast cancer in the primary tumour or in the metastasis.

Trastuzumab has substantially changed the prognosis of breast carcinomas. As HER2 over-expression/amplification is a prerequisite for treatment with trastuzumab, an accurate assessment of HER-2 status is the first step for successful treatment. In metastatic breast cancer, we routinely assess HER2 expression in the primary tumour, assuming that HER2 status remains stable through cancer progression. However, it is frequent to find reports that describe discordance between HER2 expression in primary and metastatic tumours. The aim of this paper was to verify whether HER2 status of breast carcinomas is maintained in the corresponding axillary metastasis. Immunohistochemistry was performed on 52 breast carcinomas and their matched axillary metastasis. HercepTest results were concordant in 46 out of 52 cases (88.5%). FISH proved that the differences observed were clinically relevant in only one of the 52 cases studied (98% concordance). We concluded that HER2 status was stable during axillary metastatic progression. Evaluation of gene HER2 status in axillary metastasis rather than in the primary can be useful in certain situations, e.g., small invasive component intimately mixed with in situ component and difficult to recognize in dark field, no tumor after biopsy, or axillary relapse (in this case we can find occasional de novo amplifications susceptible to trastuzumab treatment).