Molecular classification and subtype-specific characterization of skin cutaneous melanoma by aggregating multiple genomic platform data

Abstract

Purpose

Traditional classification of melanoma is widely utilized with little apparent results making the development of robust classifiers that can guide therapies an urgency. Successful seminal research on classification has provided a wider understanding of cancer from multiple molecular profiles, respectively. However, it may ignore the complementary nature of the information provided by different types of data, which motivated us to subtype melanoma by aggregating multiple genomic platform data.

Methods

Aggregating three omics data of 328 melanoma samples, melanoma subtyping was performed by three clustering methods. Differences across subtypes were extracted by functional enrichment, epigenetically silencing, gene mutations and clinical features. Subtypes were further distinguished by putative biomarkers.

Results

Functional enrichment of the subtype-specific differential expression genes endowed subtypes new designation: immune, melanin and ion, in which the first subtype was enriched for immune system, the second was characterized by melanin and pigmentation, and the third was enriched for ion-involved transmission process. Subtypes also differed in age, Breslow thickness, tumor site, mutation frequency of BRAF, PTGS2, CDKN2A, CDKN2B and incidence of epigenetically silencing for IL15RA, EPSTI1, LXN, CDKN1B genes.

Conclusions

Skin cutaneous melanoma can be robustly divided into three subtypes by SNFCC⁺. Compared with the TCGA classification derived from gene expression, the subtypes we presented share concordance, but new traits are excavated. Such a genomic classification offers insights to further personalize therapeutic decision-making and melanoma management.

https://ift.tt/2sYE39e

MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse model

Abstract

Background and purpose

Recently, imaging and high-precision irradiation devices for preclinical tumor models have been developed. Image-guided radiation therapy (IGRT) including innovative treatment planning techniques comparable to patient treatment can be achieved in a translational context. The study aims to evaluate magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning with different treatment techniques for high-precision radiation therapy (RT).

Materials and methods

In an orthotopic pancreatic cancer model, MRI/CT-based radiation treatment planning was established. Three irradiation techniques (rotational, 3D multifield, stereotactic) were performed with the SARRP system (Small Animal Radiation Research Platform, Xstrahl Ltd., Camberley, UK). Dose distributions in gross tumor volume (GTV) and organs at risk (OAR) were analyzed for each treatment setting.

Results

MRI with high soft tissue contrast improved imaging of GTV and OARs. Therefore MRI-based treatment planning enables precise contouring of GTV and OARs, thus, providing a perfect basis for an improved dose distribution and coverage of the GTV for all advanced radiation techniques.

Conclusion

An MRI/CT-based treatment planning for high-precision IGRT using different techniques was established in an orthotopic pancreatic tumor model. Advanced radiation techniques allow considering perfect coverage of GTV and sparing of OARs in the preclinical setting and reflect clinical treatment plans of pancreatic cancer patients.

https://ift.tt/2JIwrSy

Gastrointestinal CMV Disease and Tuberculosis in an AIDS Patient: Synergistic Interaction between Opportunistic Coinfections

The AIDS pandemic has made diseases such as tuberculosis, CMV disease, and other opportunistic infections more prevalent; these diseases may even be found to be associated among themselves, and the natural history of each disease may present in an unusual manner. We report the case of a 41-year-old man with HIV (CD4 of 144 cells/dL) and HCV with hematochezia due to tuberculosis in the ileocecal valve and descending colon and CMV tissue invasive disease in the esophagus and descending colon. Coinfection among tuberculosis and cytomegalovirus in the gastrointestinal tract was described only once in a patient with a recent diagnosis of HIV that affected the distal ileum and ascending colon. We will discuss the peculiarities of the case and the behavior of the immune system in the face of simultaneous opportunistic infections. This is a challenging scenario that has scarce publications and is of great clinical importance.

https://ift.tt/2JEePEg

Burkitt’s lymphoma presenting as acute appendicitis: a case report

Abstract

Appendiceal lymphomas are exceedingly rare, constituting around 0.015% of all gastrointestinal lymphoma cases. Burkitt's lymphoma is the second most prevalent pathology, diagnosed in 25.9% of patients. We report a case of a 36-year-old male admitted with acute abdominal pain with 2 days of evolution, localized in the right lower quadrant associated with hyporexia, but no fever. On examination he presented abdominal tenderness on the right iliac fossa. A diagnosis of acute appendicitis was made clinically. At the post-operative follow up, 2 weeks later, he presented a low back pain of high intensity, associated with swelling of the abdomen, night sweats, daily fevers and weight loss. The histopathological exam of the appendix revealed diffuse and transmural lymphoid proliferation. Immunohistochemistry suggested high grade B-cell lymphoma indicative of Burkitt's lymphoma. This patient was staged as a IVxB lymphoma and was submitted into polychemotherapy with a complete clinical response in 8 months.

https://ift.tt/2Jrl565

Cecal ameboma mimicking obstructing colonic carcinoma

Abstract

Ameboma is a mass of granulation tissue with peripheral fibrosis and a core of inflammation related to amebic chronic infection. The initial presentations of colonic ameboma usually include obstruction and low gastrointestinal bleeding. It may mimic colon carcinoma or other granulomatous inflammatory conditions of the colon in both the clinical presentation and the endoscopic appearance. Here, we report a case of a 45-year-old male with a presentation of abdominal pain and constipation, as well as clinical, radiological and endoscopic presentation resembling colonic carcinoma, that was managed operatively with right hemicolectomy and post-operative histopathologic finding of cecal ameboma.

https://ift.tt/2HBVemc

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation

Abstract

Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

https://ift.tt/2Jsk8dI

Spontaneous adrenal hemorrhage. Report of two cases and review of pathogenesis, diagnosis and management

Abstract

Adrenal hemorrhage represents a relatively rare condition, usually associated with meningococcal septicemia. It is an underestimated cause of acute decompensation, multiorgan failure and death, usually diagnosed post-mortem. Depending on its etiology adrenal hemorrhage is categorized as traumatic and non-traumatic. The technical advancement of imaging modalities, has made diagnosis and management more efficient. Assessment of hemodynamic stability, exclusion of a hormonal active adrenal tumor and assessment for adrenal insuffi¬ciency, are of cardinal importance. Angiographic embolization has contributed significantly in better outcomes as emergency laparotomy is associated with high morbidity and mortality rates. Hereby we present two cases of spontaneous adrenal hemorrhage associated with extensive retroperitoneal bleeding and hemodynamic instability. Both underwent angiography with one requiring embolization with favorable outcome. Investigation for exclusion of underlying adrenal tumor, adrenal insufficiency and follow-up imaging are presented in detail for both cases.

https://ift.tt/2HBVaCY