Case Report: Long-Term Survival of a Dog With Chronic Lymphocytic Leukemia Treated With Chlorambucil, Prednisolone, and Imatinib

A 7-year-old castrated male Poodle dog presented with chronic progressive lymphocytosis. Hematologic and peripheral blood smear findings included remarkable lymphocytosis with well-differentiated small lymphocytes. Cytology of bone marrow aspirate showed hypercellular integrity with infiltration of small mature lymphocytes, accounting for 45% of all nucleated cells. Flow cytometry of blood and marrow samples revealed neoplastic lymphocytes predominantly expressing the CD21 molecule. B-cell chronic lymphocytic leukemia (CLL) was diagnosed on an immunophenotypic analysis. Administrations of prednisolone and chlorambucil were initiated and the response was unremarkable. Therefore, additional treatment with imatinib was provided, which resolved the hematologic abnormalities associated with CLL. Flow cytometry after ~1 year of treatment showed normalization of the count of lymphocytes positive for CD21 and resolved hematologic lymphocytosis. The dog was followed-up for 2 years, and there were no severe adverse effects. This case indicates that imatinib may be a good option as an adjunctive therapy with prednisolone and chlorambucil treatment for CLL in dogs without treatment response.

Automatic Radiotherapy Planning for Glioblastoma Radiotherapy With Sparing of the Hippocampus and nTMS-Defined Motor Cortex

BackgroundNavigated transcranial magnetic stimulation (nTMS) of the motor cortex has been successfully implemented into radiotherapy planning by a number of studies. Furthermore, the hippocampus has been identified as a radiation-sensitive structure meriting particular sparing in radiotherapy. This study assesses the joint protection of these two eloquent brain regions for the treatment of glioblastoma (GBM), with particular emphasis on the use of automatic planning.Patients and MethodsPatients with motor-eloquent brain glioblastoma who underwent surgical resection after nTMS mapping of the motor cortex and adjuvant radiotherapy were retrospectively evaluated. The radiotherapy treatment plans were retrieved, and the nTMS-defined motor cortex and hippocampus contours were added. Four additional treatment plans were created for each patient: two manual plans aimed to reduce the dose to the motor cortex and hippocampus by manual inverse planning. The second pair of re-optimized plans was created by the Auto-Planning algorithm. The optimized plans were compared with the “Original” plan regarding plan quality, planning target volume (PTV) coverage, and sparing of organs at risk (OAR).ResultsA total of 50 plans were analyzed. All plans were clinically acceptable with no differences in the PTV coverage and plan quality metrics. The OARs were preserved in all plans; however, overall the sparing was significantly improved by Auto-Planning. Motor cortex protection was feasible and significant, amounting to a reduction in the mean dose by >6 Gy. The dose to the motor cortex outside the PTV was reduced by >12 Gy (mean dose) and >5 Gy (maximum dose). The hippocampi were significantly improved (reduction in mean dose: ipsilateral >6 Gy, contralateral >4.6 Gy; reduction in maximum dose: ipsilateral >5 Gy, contralateral >5 Gy). While the dose reduction using Auto-Planning was generally better than by manual optimization, the radiated total monitor units were significantly increased.ConclusionConsiderable dose sparing of the nTMS-motor cortex and hippocampus could be achieved with no disadvantages in plan quality. Auto-Planning could further contribute to better protection of OAR. Whether the improved dosimetric protection of functional areas can translate into improved quality of life and motor or cognitive performance of the patients can only be decided by future studies.

One-Year Outcomes of the ROBUST II Study Evaluating the Use of a Drug-Coated Balloon for Treatment of Urethral Stricture

Objective To report 1-year results of the ROBUST II study investigating the safety and efficacy of a paclitaxel-coated balloon for the treatment of recurrent urethral strictures. Methods Subjects were adult men with a single anterior urethral stricture ≤ 3 cm in length and at least 2 prior stricture treatments. After treatment with the Optilume urethral drug-coated balloon (DCB), subjects were followed through 1 year. The primary safety endpoint was the rate of treatment-related serious complications at 90 days post-procedure. Efficacy outcomes included symptomatic assessments, erectile function measured using the International Index of Erectile Function (IIEF), Qmax, and anatomic success. Results Sixteen men with an average of 4.1 prior dilations were treated with the DCB. Anatomic success was achieved at 6 months in 73%. Average IPSS improved from 18.4 to 6.0 at 1 year (P < 0.001). Qmax improved from 6.9 mL/sec to 20.8 mL/sec (P < 0.001). There was no change in IIEF. Four subjects received additional treatment within 1 year. There were no treatment-related serious complications. Conclusions Short-term follow-up of men with urethral stricture treated with the Optilume DCB showed durable anatomic results at 6 months and sustained symptomatic improvement through 1 year. Treatment with the device was safe.

Therapeutic Advances in Diabetic Nephropathy

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) in the United States. Risk factor modification, such as tight control of blood glucose, management of hypertension and hyperlipidemia, and the use of renin–angiotensin–aldosterone system (RAAS) blockade have been proven to help delay the progression of DKD. In recent years, new therapeutics including sodium-glucose transport protein 2 (SGLT2) inhibitors, endothelin antagonists, glucagon like peptide-1 (GLP-1) agonists, and mineralocorticoid receptor antagonists (MRA), have provided additional treatment options for patients with DKD. This review discusses the various treatment options available to treat patients with diabetic kidney disease.

Immunotherapy toxicity: identification and management

The widespread adoption of immunotherapy has revolutionized the treatment of various cancer types, including metastatic triple-negative breast cancer (TNBC), which has long been associated with poor prognostic outcomes. In particular, immune checkpoint inhibitors (ICIs) that target and inhibit programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have shown promising results in the treatment of patients with metastatic TNBC. However, while manipulating the immune system to induce antitumor response, ICIs can also lead to a unique set of immune-related adverse events (IRAEs), which differ from standard chemotherapy toxicities due to their immune-based origin. These toxicities require highly specific management, including guidance from multidisciplinary specialists. The primary treatment strategy against IRAEs is systemic corticosteroid use, but additional treatment approaches may also involve supportive care, additional immunosuppression, and concurrent treatment delay or discontinuation. Given the rising prevalence of ICI therapy, it is essential to educate clinicians on the presentation and management of these potentially life-threatening events so that they are identified early and treated appropriately. Using data from recent clinical trials, this review will focus on known IRAEs, particularly those seen in patients with breast cancer, and will summarize their prevalence, severity, and outcomes. We will discuss optimal strategies for early recognition and management, as well as approaches toward cautious retreatment following resolution of IRAEs.

Mucoepidermoid Carcinomas of the Larynx

Objectives: Discussions regarding the specific management and outcomes for laryngeal MEC are limited to very small, single-institution case series. To look further into the diagnosis and management of these uncommon non-squamous cell carcinomas of the larynx, we present 3 recent cases of laryngeal MEC treated at our institution. Methods: Patients at a tertiary hospital treated for MEC between October 2019 and December 2020 were retrospectively identified. Chart review, imaging analysis, and histologic slide creation were completed for all patients. Results: We identified and treated 2 patients with high-grade supraglottic and 1 patient with intermediate-grade glottic MEC. These patients presented to our clinic with a primary complaint of either gradual, worsening dysphonia, dysphagia, or both. All patients underwent laryngovideostroboscopy as well as panendoscopy with directed submucosal biopsy, which was consistent with MEC. MRI was performed in 2 of the cases further elucidating the extent of submucosal spread. PET-CT was performed in all 3 cases, and none demonstrated evidence of regional or distal metastases. Surgically, high-grade MEC lesions were treated with a total laryngectomy. The intermediate MEC lesion was managed with a supracricoid partial laryngectomy (SCPL). Surgical margins were free of tumor in all cases with no nodal metastases by modified radical neck dissection. Radiation therapy was offered to both high-grade MEC patients and declined by one. Radiation was not recommended to the patient with intermediate-grade MEC as we believed that the risk of additional treatment outweighed the benefit. Conclusion: We believe that MEC of the larynx should be considered in patients with atypical submucosal laryngeal masses. Laryngovideostroboscopy, MRI, and PET imaging may be valuable in determining the extent of the lesions and planning appropriate surgery. Postoperative radiation therapy should be considered a per tumor grade in other more studied sites, as there is no data on efficacy in laryngeal MEC.

Tranexaminezuur in de gynaecologische en senologische heelkunde: een literatuuroverzicht

Tranexamic acid in gynecological and breast surgery: a literature review In gynecological and breast surgery, intra- or postoperative blood loss can cause many complications. A large number of interventions have already been described in literature to limit intraoperative blood loss. Tranexamic acid significantly reduces the amount of vaginal blood loss in women with menorrhagia and is also recommended as a treatment for postpartum hemorrhage. Tranexamic acid has been shown to be safe and efficient in limiting blood loss in many other surgical disciplines. In this literature review, the different applications of the use of tranexamic acid in gynecological and breast surgery are explained. The conclusion is that tranexamic acid can be a safe additional treatment that can reduce the total blood loss and the risk of postoperative complications and blood transfusion in various types of gynecological and breast surgery.

Effect of Charlson Comorbidity Index and Treatment Strategy on Survival of Elderly Patients After Endoscopic Submucosal Dissection for Gastric Adenocarcinoma: A Multicenter Retrospective Study

Background: The optimal treatment strategy for elderly patients with early gastric adenocarcinoma (EGAC) after non-curative endoscopic submucosal dissection (ESD) remains unclear. The purpose of this research was to explore the effectiveness of additional treatments after ESD and the factors affecting survival in elderly patients (≥60 years of age) with EGAC.Methods: A total of 639 elderly patients (≥60 years) treated with ESD for EGAC from 2006 to 2018 were retrospectively reviewed. Positive lymphatic infiltration, submucosal infiltration, and positive/indeterminate vertical resection margins are considered high risk factors in histology. According to the risk of lymph node metastasis in patients with EAGC and the treatment strategies adopted after ESD, patients were divided into three groups: there were 484 patients in group A with low risk, 121 patients in group B with high risk, without additional treatment, and 36 patients in group C with high risk, with additional treatment. The 5- and 8-year survival rate, as well as the prognostic factors of survival rate after ESD was studied.Results: The median follow-up time was 38, 40, and 49 months, respectively. There were 3, 4, and 3 deaths related to gastric adenocarcinoma in groups A, B, and C, while deaths from other diseases were 20, 5, and 3, respectively. There were significant differences in overall survival rates between groups (94.3; 86.4; 81.2%, p = 0.110), but there was no significant difference in disease-specific survival rates (98.4; 92.7; 92.4%, p = 0.016). In the multivariate analysis, the Charlson Comorbidity Index (CCI) ≥ 2 was an independent risk factor for death after ESD (hazard ratio 2.39; 95% confidence interval 1.20–4.77; p = 0.014).Conclusions: The strategy of ESD with no subsequent additional treatment for EGAC may be a suitable option for elderly patients at high risk, especially for CCI ≥ 2.

Aflibercept as Adjunctive Treatment for Filtration Surgery in Neovascular Glaucoma

Objective: To investigate intravitreal aflibercept (IVA) injection as an adjunctive treatment to trabeculectomy with mitomycin C (TMC) and panretinal photocoagulation (PRP) for neovascular glaucoma (NVG).Materials and Methods: PRP and IVA (2 mg/0.05 ml) injection were given, and TMC was performed within 2weeks after IVA. Additional PRP, laser suture lysis, subconjunctival 5-fluorouracil injection, and bleb needlingwere performed after TMC if indicated. Best corrected visual acuity (BCVA), intraocular pressure (IOP), surgicalcomplications, and number of anti-glaucoma medications were collected.Results: Five eyes from 5 consecutive patients were included. Two eyes had proliferative diabetic retinopathy (PDR), 2 central retinal vein occlusion, and 1 ocular ischemic syndrome (OIS) (mean initial IOP: 46.8±6.8 mmHg). NVI regression occurred in one eye after PRP alone, and in one eye after PRP and IVA resulting in a good IOP control with topical medical therapy. The other 3 underwent TMC. The preoperative IOP was 34 (OIS), 54 (PDR), and 50 (PDR) mmHg. The 3-month postoperative IOP decreased to 8, 8, and 4 mmHg, respectively, and to 21, 10, and 6 mmHg, respectively, at the last visit. Only the one OIS eye required postoperative topical IOP-lowering medications. Final BCVA was improved, unchanged, and decreased in 2, 2, and 1 eye, respectively. No intraoperative/postoperative complications or NVI recurrence were observed (mean follow-up: 10.7 months).Conclusion: Intravitreal aflibercept was shown to be a potentially effective additional treatment to PRP and TMC in patients with NVG.

TIGAR Enhanced Free Ca2+ Concentration in Hepatocellular Carcinoma Cells to Accelerate the Sustained Proliferation and Drug Resistance

Background: To study the role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in hepatocellular carcinoma (HCC) and drug resistance.Methods: HCC cells (HepG2 and SMMC7721) were used in this study. Fura 2-AM was used to assess cytosolic free Ca2+ concentrations ([Ca2+]i) within the two HCC cell lines. Nimodipine (NMDP), a Ca2+ antagonist, was used to reduce cytosolic [Ca2+]i level. Proliferation of HCC was measured using cell counting kit-8 (CCK-8). The roles of TIGAR and Ca2+ in drug resistance of HCC cells were assessed using epirubicin (Epi), 5-fluorouracil (5-FU), or cisplatinum (DDP).Results: Knockdown of TIGAR significantly suppressed cell viability, reduced [Ca2+]i, restrained protein expression of Ca2+-activated cysteine proteinases (Calpain1 and 2), as well as blocked the activation of nuclear factor kappa B (NF-κB) through an increase of cytoplasmic NF-κB and reduction of nuclear NF-κB. However, overexpression of TIGAR (oeTIGAR) resulted in the opposite. Evidence also shows that oeTIGAR suppressed the sensitivity of HCC to Epi, which was retarded by NMDP as an additional treatment. TIGAR interference could enhance the sensitivity of HCCs with high TIGAR expression to drugs.Conclusions: TIGAR promoted HCC progression and induced drug resistance, and the mechanism involved was [Ca2+]i-mediated activation of Calpain 1 and 2 and NF-κB signaling.