Improved Quality of Life in Metastatic Castration-Resistant Prostate Cancer Patients Receiving Consecutive Cycles of 177Lu-PSMA I&T.

The aim of this retrospective analysis was to evaluate health-related quality of life (HRQoL) for patients with metastatic castration-resistant prostate cancer (mCRPC) receiving consecutive cycles of 177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using the reliable and validated European Organisation for Research and Treatment of Cancer core quality-of-life (QoL) questionnaire. In addition, differences in HRQoL between patients with early discontinuation of treatment because of disease progression and patients who were defined as eligible for treatment continuation were analyzed. Methods: In total, 60 mCRPC patients were included in this analysis. The European Organisation for Research and Treatment of Cancer core QoL questionnaire was completed at baseline, before each treatment cycle up to the sixth treatment cycle, and at the time of PSMA-ligand PET/CT scans after the second and fourth treatment cycles. QoL assessment included global health status, functional scales, and symptom burden during treatment. Results: Global health was significantly improved at the second and fourth cycles of 177Lu-PSMA RLT (P = 0.014 and P = 0.039, respectively). In line with this, role and emotional functioning showed significant improvements at the second and fourth treatment cycles (role functioning, P = 0.045 and P = 0.048, respectively, and emotional functioning, P = 0.035 and P = 0.007, respectively). In addition, compared with baseline, fatigue and pain were significantly alleviated at the second and fourth treatment cycles (pain, P = 0.035 and P = 0.034, respectively, and fatigue, P = 0.042 and P = 0.041, respectively). Other aspects of HRQoL, even if not significantly improved, remained stable over time, except for deterioration of fatigue at the study's end (P = 0.014) and reduction of dyspnea at the second treatment cycle (P = 0.012). Patients with early discontinuation of treatment showed a concordant decline in HRQoL. Conclusion: mCRPC patients showed significant improvement in HRQoL in the course of treatment with 177Lu-PSMA RLT. Furthermore, patients with early discontinuation of treatment showed an analogous decline in HRQoL.

Does the pattern of lymphatic drainage influence the risk of nodal recurrence in trunk melanoma patients with negative sentinel lymph node biopsy?

Abstract Background: There are conflicting data regarding the prognostic value of the lymphatic basin drainage pattern in melanoma patients and the evidence is scant in the setting of negative sentinel lymph node biopsy. Objective: To investigate whether the pattern of lymphatic basin drainage influences the risk of nodal disease in patients with melanoma of the trunk and negative sentinel lymph node biopsy. Methods: A case series of patients with trunk melanoma and negative sentinel lymph node biopsy was retrospectively evaluated. Clinicopathological features, the pattern of lymphatic drainage and nodal, metastatic, and overall recurrence-free survival were reviewed. Results: Of the 135 patients included, multiple lymphatic basin drainage was identified in 61 (45.2%). Ten of the 74 (13.5%) patients with single drainage developed nodal recurrence, compared with 2 of the 61 (3.6%) patients with multiple drainages (p = 0.04). Nodal recurrence-free survival was significantly longer in the group with multiple drainages than in the group with single drainage (175.6 vs. 138.7 months; p = 0.04). In multivariate analysis, single drainage was associated with a higher risk of nodal recurrence (HR = 4.54; p = 0.05). No significant differences in metastatic and overall recurrence-free survival were found between groups. Study limitations: Retrospective analysis, single-center study, small sample, detailed histopathologic information not always present. Conclusions: In patients with trunk melanoma and negative sentinel lymph node biopsy, multiple lymphatic basin drainage may be an independent risk factor for nodal disease recurrence. This factor may help to identify patients with negative sentinel lymph node biopsy with a higher risk of nodal recurrence.

Does the pattern of lymphatic drainage influence the risk of nodal recurrence in trunk melanoma patients with negative sentinel lymph node biopsy?

BACKGROUND: There are conflicting data regarding the prognostic value of the lymphatic basin drainage pattern in melanoma patients and the evidence is scant in the setting of negative sentinel lymph node biopsy. OBJECTIVE: To investigate whether the pattern of lymphatic basin drainage influences the risk of nodal disease in patients with melanoma of the trunk and negative sentinel lymph node biopsy. METHODS: A case series of patients with trunk melanoma and negative sentinel lymph node biopsy was retrospectively evaluated. Clinicopathological features, the pattern of lymphatic drainage and nodal, metastatic, and overall recurrence-free survival were reviewed. RESULTS: Of the 135 patients included, multiple lymphatic basin drainage was identified in 61 (45.2%). Ten of the 74 (13.5%) patients with single drainage developed nodal recurrence, compared with 2 of the 61 (3.6%) patients with multiple drainages (p = 0.04). Nodal recurrence-free survival was significantly longer in the group with multiple drainages than in the group with single drainage (175.6 vs. 138.7 months; p = 0.04). In multivariate analysis, single drainage was associated with a higher risk of nodal recurrence (HR = 4.54; p = 0.05). No significant differences in metastatic and overall recurrence-free survival were found between groups. STUDY LIMITATIONS: Retrospective analysis, single-center study, small sample, detailed histopathologic information not always present. CONCLUSIONS: In patients with trunk melanoma and negative sentinel lymph node biopsy, multiple lymphatic basin drainage may be an independent risk factor for nodal disease recurrence. This factor may help to identify patients with negative sentinel lymph node biopsy with a higher risk of nodal recurrence.

Revisiting the acute kidney injury in Wistar rats experimentally envenomated wity Bothrops jararacussu venom.

There is no consensus on whether serotherapy prevents acute kidney injury (AKI) and there is no pharmacotherapy to impede the disease. We aimed to elaborate an AKI model induced by the administration of Bothrops jararacussu (Bj) venom for preclinical studies. Male Wistar rats were randomly divided into 3 different groups: (1) Bj-IV: intravenous administration of 0.4 mg/kg Bj; (2) Bj-IP: intraperitoneal administration of 2.0 mg/kg Bj; (3) Bj-IM: intramuscular administration of 3.5 mg/kg Bj. For each corresponding control group, a 0.9% saline solution was administered. Kidneys, blood and urine samples were collected 24 or 72 h after administration of the Bj venom for renal function analysis. The IV- and IP-Bj groups presented a moderate tubular injury (score 3) and a time-dependent kidney dysfunction. In the Bj-IM group, renal tubular injury was aggravated (score 4) with collagen deposition and renal dysfunction was observed in the first 24 h: hyperfiltration, proteinuria, albuminuria and decreased fractional sodium excretion (FENa), regardless of the administered dose. Over time, the glomerular lesion was intensified, with a decrease in glomerular filtration rate (GFR; 67%), blood urea-nitrogen (BUN; 68%) and urine volume decrease (71%). Proteinuria and tubular function returned to control levels after 72 h. We attributed the pronounced kidney injury and reduced filtration function in the Bj-IM to the muscle damage provoked by the IM administration. We concluded that the Bj-IM is the best preclinical model of AKI with the monitoring of the progression of renal function in the periods of 24 and 72 h.

Doxycycline treatment reestablishes renal function of Wistar rats in experimental envenomation with Bothrops jararacussu venom.

Acute kidney injury is one of the main complications of ophidian accidents and the leading cause of death in patients who survive the initial damage effects of venom. The hypothesis proposed in this investigation is that the pharmacological repositioning of doxycycline (doxy) attenuates renal injury provoked by Bothrops jararacussu (Bj) venom. Male Wistar rats were subjected or not (control) to experimental envenomation with Bj venom (3.5 mg/kg, im). Doxy (3 mg/kg, ip) was administered 2 h after envenoming. Envenomation with Bj venom promoted tissue damage in the renal cortex (moderate degree, score 3) in 24 h associated with decreased glomerular and tubular function, which promoted proteinuria and polyuria. Doxy treatment prevented the increase in urinary volume in 3 times, the increase in plasma creatinine in 33%, the increase in blood urea-nitrogen accumulation in 65%, the increase in urinary Na+ excretion in 2 times, marked proteinuria and kidney cortex injury induced by Bj envenomation. Bj venom promoted increase in protein content (66%) and reduction of 45% (Na++K+)-ATPase activity in the renal cortex. The enzyme was detected mainly in the luminal membrane. Doxy treatment was effective in preventing the mentioned alterations, maintaining (Na++K+)-ATPase in the basolateral membranes.