Evidence of the role of the vagal nerves as a monitor in the gastrointestinal-renal axis of natriuresis in human: Effects of vagotomy

This study aimed to investigate the mechanism of gastrointestinal regulation of natriuresis. Sixteen subjects without (group I) and sixteen subjects with a truncal vagotomy (group II), were given a daily diet of 18 mmol of sodium for 5 days (D1–D5). The sodium deficit for this period was calculated for each subject and on the morning of day-6 (D6), their cumulative deficit (E) was given as 3% NaCl. In both groups the subjects were divided to receive the hypertonic saline either orally (Ior, IIor) or intravenously (Iiv, IIiv). During the period of low sodium diet when compared to group II subjects of group I (1) had a greater weight loss (p < 0.005), (2) demonstrated a larger drop in pulse pressure (p < 0.005), (3) achieved a positive sodium equilibrium later (D5 vs D4) and (4) developed a greater sodium deficit (p < 0.005). During the two 12 h periods of D6, both Ior and Iiv exhibited greater natriuresis during the first 12 h period (p < 0.0001) whereas both IIor and IIiv did so during the second 12 h period (p < 0.0001). On D6 Ior excreted the greatest percentage of E (E%; 35.63% ± 3.12%, p < 0.0001) compared to Iiv (17.06% ± 1.78%), IIor (16.03% ± 3.54%) and IIiv (15.39% ± 2.77%) whereas E% was not different between the other subgroups. These results indicate that the differential natriuresis between oral and intravenous sodium loading in previously sodium deprived subjects, is due to a mechanism in which the vagal nerves play a significant role as part of neural reflex or via a natriuretic hormone. © 2017 Elsevier B.V

Evidence for Efficacy of Treatment with the Anti-PD-1 Mab Nivolumab in Radiation and Multichemorefractory Advanced Penile Squamous Cell Carcinoma

Penile squamous cell carcinoma (PeSCC) is a rare tumor and advanced PeSCC is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. We describe for the first time a case with advanced chemoradiation refractory PeSCC who had documented response to active immunotherapy with the immune checkpoint inhibitor, anti-programmed death-1 monoclonal antibody Nivolumab. The patient suffered from a poor prognosis human papillomavirus-negative PeSCC, with a somatic inactivation mutation of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in tumor cells, and treatment with Nivolumab resulted in a partial response to therapy and significant tumor shrinkage. Histology transitions and alterations in tumorinfiltrating cytotoxic CD8+ T-cell lymphocytes, programmed death ligand-1 expression on tumor cells and immune cells in tumor lesion biopsies pretreatment and posttreatment with Nivolumab were observed and described. In conclusion, in patients with metastatic PeSCC active immunotherapy combinations with an anti-programmed death-1/programmed death ligand-1 agent may be beneficial and further relative clinical studies are required. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

A retrospective open-label uncontrolled study of Epoetin zeta on the treatment of chemotherapy-induced anemia in solid tumors

Purpose: This is a single-center uncontrolled retrospective study to evaluate the efficacy and safety of the biosimilar epoetin zeta after approval in chemotherapy-induced anemia (CIA). Methods: Patients screened were >18 years old suffering from solid malignancies and CIA with Hg ≤10 or <11 g/dl if symptomatic anemia. Patients had measurable disease by TNM and Eastern Cooperative Oncology Group (ECOG). Patients were treated for at least 12 weeks and the primary endpoint was to determine the incidence of blood transfusions, and secondarily, the overall safety and efficacy defined as ≥1 g/dl rise in Hb concentration or ≥40,000 cells/μl rise in reticulocyte count. Quality of life was assessed with ECOG performance status (PS) and functional assessment of cancer therapy-anemia (FACT-An) score. Results: 1287 patients with median Hb 9.3 g/dl (range 8.3–10.6) were enrolled and included in the evaluation. Median age was 63 years (range 33–78). 74% of patients were stage III/IV. Patients received epoetin zeta subcutaneously at fixed 40,000-IU once weekly. Blood transfusions were given in 178 patients (13.8%; 95% CI 11.9–15.6%). Appropriate response was observed in 79% patients by week 4, 87% by week 8, and 91% by week 12. A mean Hb increase of 2.5 g/dl was observed by week 12 which correlated with an improvement in PS and Fact-An score. Thrombotic events occurred in 5.2% (95% CI 3.4–7.1%) of patients. Conclusions: Epoetin zeta is effective in palliation and treatment of CIA in patients with solid tumors. Overall, it is well tolerated and safe even in patients with increased disease burden. © 2017, Springer-Verlag Berlin Heidelberg

Efficacy and Safety of Neoadjuvant Treatment with Bevacizumab, Liposomal Doxorubicin, Cyclophosphamide and Paclitaxel Combination in Locally/Regionally Advanced, HER2-Negative, Grade III at Premenopausal Status Breast Cancer: A Phase II Study

Background: In the era of personalized therapy, targeted treatment in specific patient populations is mandated. Objective: We evaluated the efficacy and safety of neoadjuvant treatment on locally advanced breast cancer (LABC) with a monoclonal agent against vascular endothelial growth factor (VEGF), bevacizumab plus chemotherapy combination of liposomal doxorubicin, cyclophosphamide and paclitaxel (PLAC-B). Methods: Patients enrolled were at premenopausal status and characterized by human epidermal growth factor receptor 2 (HER2)-negative, hormone-receptor positive (estrogen receptor/progesterone receptor-positive [ER/PR+]) or triple-negative (TNBC), LABC (T > 3 cm), with high-grade ductal carcinoma. Patients had to have a measurable disease and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, with adequate hematologic, renal, and hepatic function. Patients received intravenous liposomal doxorubicin 30 mg/m 2 , cyclophosphamide 600 mg/m 2 , paclitaxel 120 mg/m 2 , and bevacizumab 8 mg/kg on day 1 of 15-day cycles for four cycles (four administrations as neoadjuvant treatment). The primary endpoint was complete clinical (cCR) and pathologic (pCR) response rates, while secondary endpoints included safety, breast-conserving surgery (BCS) conversion rate, and disease-free survival (DFS). Results: Sixty-two women were enrolled; 20 were ER/PR+ and 42 had TNBC. All underwent surgery, six received mastectomy, and 56 (90.3%) received BCS, with an equal conversion rate from initial indication for mastectomy. cCR was 25.8%. pCR in the breast and axilla occurred in 24 patients (38.7%). pCR was 42.9% for TNBC and 30% for ER/PR+. Hematologic adverse events (AEs) included neutropenia (74.2% total; 22.6% grade 3 [G3]) and febrile neutropenia (6.5% G3); non-hematologic G3 AEs included nausea (6.5%), mucositis (9.7%), and infection (3.2%), all of which were managed without negative sequelae. Over a 3-year follow-up, all patients were alive and DFS was 87.1%. Conclusion: PLAC-B as neoadjuvant treatment of this subpopulation with TNBC and ER/PR+ patients is effective and safe. Further studies are necessitated. © 2018, Springer International Publishing AG, part of Springer Nature

Capecitabine, Oxaliplatin, Irinotecan, and Bevacizumab Combination Followed by Pazopanib plus Capecitabine Maintenance for High-Grade Gastrointestinal Neuroendocrine Carcinomas

Objectives:Gastrointestinal neuroendocrine carcinoma (NEC) is a lethal, uncommon, and understudied neoplasm. We present the efficacy and safety of first-line capecitabine (CP), oxaliplatin, irinotecan, and bevacizumab (CAPOXIRI-BEV) combination followed by pazopanib plus CP maintenance therapy in patients with advanced high-grade poorly differentiated gastrointestinal NEC.Methods:This was a two-stage phase II study conducted at multiple institutions. Patients were consecutively enrolled and had advanced NEC of the colon or small bowel. Patients received irinotecan 125 mg/m2, oxaliplatin 80 mg/m2on day 1, CP 1000 mg/m2twice daily on days 1 to 14, plus bevacizumab 8 mg/kg on day 1 for six 21-day cycles. Maintenance therapy was given to those who responded (complete response/partial response) or had stable disease after 6 cycles with CAPOXIRI-BEV with pazopanib 800 mg daily plus CP 1600 mg/m2daily on days 1 to 14 every 3 weeks until disease progression or unacceptable toxicity. Patients who progressed on CAPOXIRI-BEV received standard etoposide-carboplatin. The primary endpoint was overall response rate.Results:Twenty-two patients were enrolled of whom 19 were evaluable. The median age was 60 years. The overall response rate (3 complete response/6 partial response) was 47.4% (95% confidence interval: 29.5-76.1), the overall disease control rate was 78.9% (95% confidence interval: 62.6-99.6), and, at median 30 (11 to 41 mo) months' follow-up, 5 patients (26.3%) were still alive. Median progression-free survival was 13 months, and the 1-year progression-free survival rate was 52.6%. The median overall survival was 29 months. The median overall survival of the 9 patients who responded versus those with stable disease/progressive disease was 30.5 versus 14 months, respectively. The median duration of response was 16 months. Predictable toxicity was observed.Conclusions:First-line CAPOXIRI-BEV followed by pazopanib plus CP maintenance therapy for advanced NEC demonstrates promising efficacy and predictable toxicity. Further investigation is warranted. © 2020 Lippincott Williams and Wilkins. All rights reserved