Tryptophan Modulation in Cancer-Associated Cachexia Mouse Models.

Cancer cachexia is a multifactorial syndrome that interferes with treatment and reduces the quality of life and survival of patients. Currently, there is no effective treatment or biomarkers, and pathophysiology is not clear. Our group reported alterations on tryptophan metabolites in cachectic patients, so we aim to investigate the role of tryptophan using two cancer-associated cachexia syngeneic murine models, melanoma B16F10, and pancreatic adenocarcinoma that is KPC-based. Injected mice showed signs of cancer-associated cachexia as reduction in body weight and raised spleen weight, MCP1, and carbonilated proteins in plasma. CRP and Myostatin also increased in B16F10 mice. Skeletal muscle showed a decrease in quadriceps weight and cross-sectional area (especially in B16F10). Higher expression of atrophy genes, mainly Atrogin1, was also observed. Plasmatic tryptophan levels in B16F10 tumor-bearing mice decreased even at early steps of tumorigenesis. In KPC-injected mice, tryptophan fluctuated but were also reduced and in cachectic patients were significantly lower. Treatment with 1-methyl-tryptophan, an inhibitor of tryptophan degradation, in the murine models resulted in the restoration of plasmatic tryptophan levels and an improvement on splenomegaly and carbonilated proteins levels, while changes in plasmatic inflammatory markers were mild. After the treatment, CCR2 expression in monocytes diminished and lymphocytes, Tregs, and CD8+, were activated (seen by increased in CD127 and CD25 expression, respectively). These immune cell changes pointed to an improvement in systemic inflammation. While treatment with 1-MT did not show benefits in terms of muscle wasting and atrophy in our experimental setting, muscle functionality was not affected and central nuclei fibers appeared, being a feature of regeneration. Therefore, tryptophan metabolism pathway is a promising target for inflammation modulation in cancer-associated cachexia.

[Cytomegalovirus reactivation in patients with immune-mediated gastritis]. / Reactivación de citomegalovirus en pacientes con gastritis inmunomediada.

INTRODUCTION: Reactivation of cytomegalovirus can complicate the evolution of patients with gastritis induced by immune checkpoint inhibitors. METHODS: The experience in our center is described and a review of the literature is performed. RESULTS: A case of severe gastritis induced by treatment with a programmed cell death receptor-1 (anti-PD1) inhibitor, associated with reactivation of cytomegalovirus (CMV) is described. In the systematic review, we identified 5 cases of immune-related gastritis associated with CMV reactivation. Ganciclovir treatment contributed to clinical improvement in most patients. CONCLUSION: The early identification of a CMV infection in patients with severe or refractory immune-related gastritis will allow the initiation of targeted treatment, and may avoid increasing immunosuppressive therapy.

A Patient with an Ileocecal MiNEN and a Synchronous Squamous Non-Small-Cell Lung Cancer: Case Report and Review of the Literature.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare tumors composed of two different histological components, one of which is of a neuroendocrine origin. Given its suggested underdiagnosis and consequent low prevalence, no clear diagnostic and treatment guidelines are available, and treatment usually follows regimens similar to that of the most aggressive component. On the other hand, multiple primary tumors (MPTs) are also rare neoplastic entities that usually confer a challenge regarding treatment options, for a regimen that comprises both the primary and the synchronous/metachronous malignancy should be used. Here, we discuss the challenging diagnostic and therapeutic management of a patient with an ileocecal MiNEN that presented along with a synchronous squamous non-small-cell lung cancer (SQ-NSCLC). The patient presented with intestinal obstruction symptoms for which he underwent an emergency resection of the ileocecal MiNEN. An initial CT scan showed an additional lung mass later identified as an SQ-NSCLC after bronchoscopy biopsy analysis. Given the rapid hepatic metastatic progression, palliative platinum-based chemotherapy was initiated, with an adequate response of the local and metastatic lesions of the MiNEN, but suggested platinum resistance and progression of the pulmonary neoplasm. Second-line treatment with pembrolizumab directed for the SQ-NSCLC was initiated; however, it was stopped after immune-mediated toxicities developed. A third-line chemotherapy scheme with carboplatin/gemcitabine was initiated, but central nervous system (CNS) progression developed, with the patient dying 11 months after initial diagnosis.

An unusual case of air within the bladder wall: bladder pneumatosis?

Emphysematous cystitis is a potentially life-threatening condition characterized by the amassing of gas within the wall of the bladder, as a result of infection by gas-forming organisms. However, the amassing of gas in the wall of the bladder does not always result from an infectious etiology. Here we report the case of a patient diagnosed with lung cancer and treated with chemotherapy, where there was air within the bladder wall accompanied by pneumoperitoneum. The presence of an infectious etiology was not clear, and the patient responded successfully to medical treatment. Although emphysematous cystitis is the most common diagnosis, the presence of gas within the wall of the bladder is a sign and not a disease per se. In our opinion, the case displays similar characteristics to those of pneumatosis cystoides intestinalis, and for this reason we refer to it as bladder pneumatosis.