Novel Treatment of Melanoma: Combined Parasite-Derived Peptide GK-1 and Anti-Programmed Death Ligand 1 Therapy.

Recent successes in the development of new therapies for metastatic melanoma, such as mitogen-activated protein kinase pathway inhibitors, anticytotoxic T lymphocyte-associated antigen-4, and programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) pathway-blocking antibodies, as well as combination strategies, all yielded promising results, changing the continually evolving landscape of therapeutic options for patients with melanoma. One promising new treatment modality is based on the use of immunomodulatory monoclonal antibodies that enhance the function of components of the antitumor immune response such as T cells or block immunologic checkpoints that restrain effective antitumor immunity. Program death-1 receptor and its ligand, PD-L1, is a major mechanism by which a tumor suppresses T cell-mediated antitumor immune responses. Studies in mice have shown that GK-1, an 18 amino acid peptide from Taenia crassiceps cisticerci, has the potential to be used as a primary or adjuvant component for the treatment of cancers by stimulating proinflammatory cytokines. The authors hypothesized that treatment with GK-1 in combination with anti-PD-L1 will increase survival in mice bearing melanoma tumors. C57BL/6 mice were injected with B16-F10-luc2 cells and separated into four groups: control, GK-1, anti-PD-L1, and GK-1/anti-PD-L1. The tumor sizes were measured and monitored using calipers and bioluminescence. The GK-1 peptide in combination with anti-PD-L1 showed significantly longer survival (34 days) compared with the other groups (23-27 days). This means an increase; survival increased 47.82% in the mice treated with GK-1+anti-PD-L1, 21.7% in mice treated with GK-1 alone, and 6.08% in those mice treated with anti-PD-L1 only. Blood samples were collected at days 0, 14, and at euthanization or end of the experiment and monitored for cytokines using mouse-specific V-PLEX Proinflammatory Panel. A decrease in TNF-α, IL-4, IL-5, IL-6, and IL-10 serum levels was observed in the GK-1/anti-PD-L1 combination group that may explain the beneficial effects of the combination treatment in prolonging the life of mice bearing melanoma. The data indicate that GK-1/anti-PD-L1 combined therapy affectively increases survival and warrants further clinical investigations.

[Jejunal perforation secondary to pulmonary mucoepidermoid carcinoma metastasis. Case report and review]. / Perforación yeyunal secundaria a metástasis de carcinoma mucoepidermoide pulmonar. Reporte de caso y revisión de la literatura.

BACKGROUND: The first reported case of intestinal perforation secondary to metastatic lung carcinoma was reported in 1957. Intestinal metastases are present in up to 1.8% of the cases, with small bowel obstruction as the most common clinical presentation. CLINICAL CASE: An 89 year-old male, who was diagnosed with a high-grade pulmonary mucoepidermoid tumour 2 months previously. The patient was admitted to the hospital for 3 days due to diffuse colic abdominal pain of moderate to severe intensity, accompanied by nausea and gastric vomiting, as well as 2 episodes of bloody bowel movements. On physical examination, the patient was noted to have tachycardia and tachypnoea, as well as clinical signs of acute abdomen. He had white cells of 24,900 per mm3, and 87% neutrophils. Exploratory laparotomy was performed, which showed a bowel perforation associated with a tumour mass 15cm beyond the angle of Treitz. Bowel resection and primary anastomosis were performed. The histopathological analysis reported the diagnosis of a high-grade mucoepidermoid tumour with small bowel and mesentery with disease-free surgical margins. Unfortunately the patient had a fatal outcome secondary to hospital-acquired pneumonia. CONCLUSION: The cases of metastases to small bowel are extremely rare, and to our knowledge this is first case reported in Mexico. The patient described went to the emergency room with gastrointestinal bleed and intestinal perforation that required urgent surgical intervention with small bowel resection and primary anastomosis. Unfortunately the patient died secondary to hospital acquired pneumonia.

Clinical Scenarios for Discordant Anti-Xa.

Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several "day to day" clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.

Hematological Effects, Serum, and Pulmonary Cytokine Profiles in a Melanoma Mouse Model Treated with GK1.

OBJECTIVE: In a previous study, we demonstrated the therapeutic efficacy of a subcutaneous injection of GK1 peptide in a melanoma mouse model, effectively increasing the mean survival time by 42.58%, delaying tumor growth, and increasing intratumoral necrosis compared with the control. As a first approach to investigate the anti-melanoma effect of GK1, this study was carried out to determine the hematological effects along with both serum and lung cytokine profiles in a melanoma lung metastatic model. MATERIALS AND METHODS: Thirteen C57BL6 female mice were transfected in the lateral tail vein with 2×10(5) B16-F0 melanoma cells. After 7 days, mice were separated in two different groups and treatments were initiated (day 0): The GK1-treated group (seven mice) were injected every 5 days intravenously with GK1 (10 µg) in the lateral tail vein, and the control group (six mice) were injected every 5 days with intravenous saline solution. Blood samples were collected every 5 days from day 0; tumor samples were obtained for cytokine measurements on the day of sacrifice. RESULTS: In the peripheral blood, mice treated with GK1 presented a statistically significant decrease in IFN-γ (p<0.05), and lymphocytes tended to be lower compared with the control mice (p=0.06). Lung metastatic analysis demonstrated a significant increase in IFN-γ and IL-12p70 (p<0.05); a significant decrease in IL-17, IL-4, IL-22, IL-23, and IL-12p40 (p<0.05); and a marginal decrease in IL-1ß (p=0.07) compared with the control. DISCUSSION: Our results suggest that an intratumoral increase of cytokines with antitumor activity along with an intratumoral decrease of cytokines with protumor activity could explain, in part, the anti-melanoma effects of GK1 in a lung metastatic melanoma mouse model. Further studies must be performed to elucidate the precise mechanisms of action for GK1 peptide against melanoma, and their eventual application in humans.

The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

PURPOSE: The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal. EXPERIMENTAL DESIGN: C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 µg/100 µL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 µL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C). RESULTS: The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (p<0.05) in the treated mice. The overall survival rates obtained with surgical treatment at 6 months were 83.33% for group A, 40% for group B, and 0% for group C, with significant differences (p<0.05) among the groups. CONCLUSIONS: The GK1 peptide demonstrated therapeutic properties in a mouse melanoma model, as treatment resulted in a significant increase in the mean survival time of the treated animals (42.58%). The potential for GK1 to be used as a primary or adjuvant component of chemotherapeutic cocktails for the treatment of experimental and human cancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

[Deep neck abscess. Factors related to reoperation and mortality]. / Absceso profundo de cuello. Factores asociados con la reoperación y mortalidad.

BACKGROUND: Deep neck abscesses are major complications that arise of odontogenic, pharyngeal, or cervicofacial foci, mainly in patients with morbidities that facilitate the spread to other spaces. Many of them require surgical treatment, and an appropriate evaluation and surgical drainage is required to obtain the best results. AIM: To identify factors which relate to reoperation and mortality in patient submitted to surgical treatment due to deep neck abscess. METHODS: Review of all patients with deep neck abscess who underwent surgical treatment in a Head and Neck Surgery Department in a third-level hospital during a two year period. RESULTS: There were 87 patients, 44 of which were female. The median age was 49 years old. Thirty-five patients (40%) had comorbidities, diabetes mellitus being the most common, found in 30 (34%) patients. Twenty-one patients (24%) required reoperation (primarily due to inadequate surgical drainage). The risk factors identified with it were presence of comorbidities (mainly diabetes mellitus) (p< 0.05), multiple deep neck spaces involvement (p< 0.001) and an ASA score of three or above (p< 0.01). Eight patients died, for a mortality of 9%. The factors related to mortality were multiple deep neck spaces involvement (p< 0.01), bilateral involvement (p< 0.05) and reoperation (p< 0.001). CONCLUSION: Deep neck abscesses appropriate evaluation and a complete surgical drainage of all deep space neck abscesses are primordial to avoid reoperation and improve survival.

Antecedentes: los abscesos profundos de cuello son complicaciones de infecciones, principalmente de origen odontogénico y de vías aéreas superiores, que afectan con mayor frecuencia a pacientes con morbilidades que favorecen la diseminación de la infección. Muchos requieren tratamiento quirúrgico, evaluación y drenaje apropiado para obtener los mejores resultados. Objetivo: identificar los factores relacionados con la reoperación y la mortalidad en pacientes con drenaje quirúrgico por absceso profundo de cuello. Material y métodos: estudio longitudinal, retrospectivo, observacional y comparativo efectuado con base en la revisión de todos los pacientes con absceso profundo de cuello que se operaron en un servicio de cabeza y cuello de un hospital de tercer nivel. Resultados: se estudiaron 87 pacientes, 44 de ellos eran mujeres. La mediana de edad fue de 49 años. El 40% tenían comorbilidades (35 pacientes) y la diabetes melltitus fue la más frecuente en 30 pacientes (34%). Se reoperaron 21 pacientes (24%), la mayoría por drenaje incompleto. Los factores de riesgo identificados fueron: comorbilidades (principalmente diabetes mellitus) (p< 0.05), mayor número de espacios afectados (p< 0.001) y una escala de ASA III o mayor (p< 0.01). La mortalidad fue de 9% (ocho pacientes). Los factores relacionados con mortalidad fueron: mayor número de espacios afectados (p< 0.01), afectación bilateral (p< 0.05) y reoperación (p< 0.001). Conclusión: en abscesos profundos de cuello la evaluación preoperatoria y el drenaje quirúrgico completo de todos los espacios afectados son primordiales para evitar la reoperación y mejorar la supervivencia.

[Surgical practice in the Mexican Empire]. / El ejercicio de la cirugía en el imperio mexica.

The prehispanic medicines of Mexico are considered as testimony of the splendor of the Meso-American cultures; their great scientific advance and technical allowed them to accumulate a vast collection of clinical and pathological data based on the observation and experimentation. They integrated a nomenclature medical surgical that reflected their advance in those fields of the knowledge, where the anatomy and surgery occupied a preponderant paper. The medicine was known generically as ticiotl, of where it derives the term tícitl for the doctor. In their concept health-illness the limits among the magic, religion and the empiricism for natural causes were not clear, therefore they considered that the divine, human or natural origin of the illnesses influenced in an important way in its nature. Inside this complex causal system, the illnesses caused by the gods, spirits and celestial beings were considered as hot, while those caused by beings of the other realm were cold. The practice of the medicine had a very established organization designing a very advanced system of specialties that allowed them to accumulate a vast experience for the handling of chronic and acute illnesses in different progression phases, which managed with an integral therapy that had a plurality of resources of vegetable origin, animal, and mineral. The surgery was designated as texoxotlaliztli and its cures tepatiliztli. The surgeon was designated as texoxotlaticitl and it developed advanced techniques in the handling of sutures, wounded, drainage of abscesses, fractures and joint dislocations, pterygium, tonsillitis, circumcision, and amputations.