Ibrutinib Monotherapy as Bridge-to-Transplant for Relapsed/Refractory Primary Oculo-Cerebral Lymphoma.

INTRODUCTION: Primary central nervous system lymphoma is an uncommon form of extranodal non-Hodgkin's lymphoma, with increasing incidence, a relatively aggressive course and a poor 5-year survival. Because of its localization, the therapeutic compounds used in this disease must be able to pass through the blood-brain barrier. Chemotherapy regimens based on high-dose methotrexate are currently the standard of care for all patients who can tolerate such drugs. Autologous stem cell transplantation is indicated for malignant lymphomas in the relapsed/refractory setting. METHODS: Three patients, with a median age of 60 years, range 53-64, were diagnosed with primary CNS lymphoma, and treated with ibrutinib monotherapy in the Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania, between September 2018 and November 2020 All the patients were relapsed-refractory following high-dose methotrexate chemotherapy. We present our experience using ibrutinib monotherapy-based treatment as a bridge-to-transplant option on a single-center case series and a review of the literature in this field. RESULTS: Two of the patients were given ibrutinib as a second line therapy, both achieving complete remission and being eligible for an autologous stem cell transplantation. The third patient achieved a short remission using six cycles of systemic chemotherapy, but was started on ibrutinib monotherapy, with limited results. CONCLUSION: Our data is limited, and these results should be confirmed by multicentric clinical trials and should be regarded as a single-center case series, with all its limitations. Still, it brings forward a new therapeutic option for this rare subtype of malignant lymphomas, which if left untreated has a dismal prognosis.

T4 retroperitoneal liposarcoma. Challenges of big size sarcomas surgical treatment.

Our article presents some of the challenges of the surgical treatment of T4 (>15 cm) retroperitoneal liposarcomas (up to 65∕56∕30 cm, 25.5 kg) series of cases treated by the Department of Surgical Oncology, Prof. Dr. Ion Chiricuta Oncology Institute, Cluj-Napoca (IOCN), Romania, with illustrations, insisting on important blood vessels and nerves dissection and preservation and discussions of strategies with references to important articles from the last 10 years specialty literature. Challenges do not come only from intraoperative difficulties but also from establishing the right attitude from the extent of resection and oncological safety point of view, the role of the pathologist being very important because histological subtype and completeness of the resections are the most important prognostic factors for such tumors. Despite all today available aids in decision making, like nomograms or high-resolution imagery, sometimes this decision is to be taken intraoperative based on surgeon's expertise and skills. That is why is strongly advised that such cases to be treated in high-volume specialized tertiary centers of surgical oncology.

A narrative review of central nervous system involvement in acute leukemias.

Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although asymptomatic or with unspecific symptoms, CNS leukemia should be assessed in both AML/ALL patients, through a combination of flow cytometry and cytological analysis of CSF. Intrathecal therapy (ITT) is a preventive measure for CNS involvement in AML and ALL, still much research is needed in finding the appropriate target that would dramatically lower CNS involvement in acute leukemia.

Current status of imaging diagnosis in the transplanted kidney. A review of the literature with a special focus on contrast-enhanced ultrasonography.

OBJECTIVES: Ultrasonographic scanning is currently the most widespread imaging diagnostic procedure. The method provides real-time morphological, vascular and elastographic information in a non-invasive manner. In recent years, harmonic vascular examination has become accessible using intravenous contrast agents. In urological pathology, this procedure is used in the detection and evaluation of vascular and ischemic complications, in the classification of complex cysts according to the Bosniak system, also in the renal lesions with uncertain etiology and in acute pyelonephritis for the detection of abscesses. The contrast agent (SonoVue) is angiospecific and can be used in patients transplanted immediately after surgery without adverse effects or impaired renal function. Thus, it is desirable to be used in the nephrological pathology of the renal graft and to develop diagnostic models based on the evaluation of renal microvascularization, as well as the quantitative data resulting from the graphical representation of the specific parameters. The purpose of this review is to evaluate the current state of the literature regarding the place and role of contrast substance ultrasound in the early diagnosis of acute renal graft dysfunction and to make a differential diagnosis of this pathological entity. METHOD: This review quantifies the role of contrast ultrasound in the diagnosis of acute complications of the renal graft. The research was conducted based on the databases PubMed, MedScape, Cochrane, according to the search criteria such as contrast-enhanced ultrasound + kidney transplant, "time intensity curves" + "kidney transplant", filtered for the period 2004-2018. RESULTS: In the nephrological pathology of the renal graft, contrast-enhanced ultrasound is a valuable tool, superior to Doppler ultrasound in predicting the evolution of the renal graft, identifying very small early defects in renal microvascularization. A number of studies succeeded in identifying acute graft dysfunction, some of which establish its etiology - humoral rejection versus acute tubular necrosis. On the other hand, the contrast-enhanced ultrasound parameters do not have the ability to distinguish between cellular and humoral rejection. CONCLUSIONS: If, at present, the histopathological examination is the only one that can differentiate with certainty the cause of acute renal graft dysfunction, we consider that contrast-enhanced ultrasound, as a non-invasive imaging technique, opens a favorable perspective for increasing the survival of the renal graft and decreasing the complications in the renal transplant. The combination of other ultrasound techniques, together with contrast-enhanced ultrasound, could lead to the development of new diagnostic models.

Contrast-enhanced ultrasonography in the initial evaluation of the kidney graft function: a pilot study.

AIM: Our study aimed to assess the usefulness of contrast-enhanced ultrasound (CEUS) in the initial evaluation of the graft function. MATERIALS AND METHOD: A cross-sectional study was conducted in the early postoperative period on patients with kidney transplantation, between September 2017 to November 2018. Two groups of patients were investigated; delayed graft function (DGF) and early graft function (EGF). All patients were examined by grey scale, Doppler ultrasound and CEUS. RESULTS: Nineteen patients, aged from 23 to 64 years (mean age 50 years), 7 in the DGF group and 12 in the EGF group were evaluated. The resistive index (RI) show significantly higher values in the DGF group at the level of upper interlobar artery (p=0.025) and medium interlobar artery (p=0.02). The CEUS investigation shows a greater region of interest (ROI) area (p=0.02) and lower values for wash-out area under the curve (WoAUC) (p=0.047) and respectively wash-in and wash-out area under the curve (WiWoAUC) (p=0.031) for the DGF group. The quality of fit (QoF) proved lower in the DGF group either for evaluation of global graft (p=0.012), cortex (p=0.025), or medulla (p=0.009).A significant relationship among all patients was found between the glomerular filtration rate (GFR) [ml/min] and the renal artery fall time (FT) [s] (p=0.012), WoAUC [a.u.] (p=0.03), and WiWoAUC [a.u.] (p=0.024). The arterial QoF [%] was associated with the arterial ROI area (p=0.048). CONCLUSIONS: Intensity CEUS parameters WoAUC and WiWoAUC may be useful to diagnose and follow-up grafts with delayed function. Additional studies on larger cohorts are required for the recommendation of CEUS as a routine evaluation of the transplanted kidney.

Prospective investigation of pain associated with ultrasound- and computed tomography-guided percutaneous biopsies in oncological patients.

AimsThe present study aims to investigate the pain, anxiety and other factors that are associated with percutaneous computed tomography (CT)- and ultrasound (US)-guided biopsies of tumors.Material and MethodsThe study prospectively included 60 consecutive patients, of which 24 underwent CT-guided biopsies and 36 US-guided biopsies. The location of targeted tumors was within the thorax, abdomen, pelvis, and limbs. A questionnaire containing numerical rate scales (0-10) regarding procedural and post-procedural pain, anxiety, and other associated parameters was filled out by each patient 2-6 hours after the procedure. CT and ultrasound parameters were compared.  The two groups were then pooled together in order to compare pain scores per targeted organ and to analyze the parameters that were associated with pain.ResultsThere was no significant difference between the CT and US group with the exception of the positional discomfort, which was higher in the CT group (p=0.003). The average procedural pain score (2.0) was significantly higher than the post-procedural pain (1.3, p=0.006) and the phlebotomy pain (0.8, p<0.0001). There was no significant difference between the targeted organs with regards to the pain score. The factors that showed a positive correlation with the procedural pain were procedure-related anxiety (p=0.005), positional discomfort (p=0.01), and phlebotomy pain (p=0.0008). The pre interventional use of an analgesic was negatively correlated with the procedural pain (p=0.02).ConclusionsCT- and US- guided percutaneous biopsies are associated with low levels of pain that are generally well tolerated by patients irrespective of the targeted organ.