Stimuli-Responsive Hydrogel Microcapsules Harnessing the COVID-19 Immune Response for Cancer Therapeutics.

The combination of gene therapy and immunotherapy concepts, along recent advances in DNA nanotechnology, have the potential to provide important tools for cancer therapies. We present the development of stimuli-responsive microcapsules, loaded with a viral immunogenetic agent, harnessing the immune response against the Coronavirus Disease 2019, COVID-19, to selectively attack liver cancer cells (hepatoma) or recognize breast cancer or hepatoma, by expression of green fluorescence protein, GFP. The pH-responsive microcapsules, modified with DNA-tetrahedra nanostructures, increased hepatoma permeation by 50 %. Incorporation of a GFP-encoding lentivirus vector inside the tumor-targeting pH-stimulated miRNA-triggered and Alpha-fetoprotein-dictated microcapsules enables the demonstration of neoplasm selectivity, with approximately 5,000-, 8,000- and 50,000-fold more expression in the cancerous cells, respectively. The incorporation of the SARS-CoV-2 spike protein in the gene vector promotes specific recognition of the immune-evading hepatoma by the COVID-19-analogous immune response, which leads to cytotoxic and inflammatory activity, mediated by serum components taken from vaccinated or recovered COVID-19 patients, resulting in effective elimination of the hepatoma (>85 % yield).

Antibody response in elderly vaccinated four times with an mRNA anti-COVID-19 vaccine.

The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those not exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 IgG II Quant assay) and neutralizing capacities (spike SARS-CoV-2 pseudovirus Wuhan and Omicron BA.1 variant) were measured after the third and fourth doses of a COVID-19 mRNA vaccine among 46 elderly residents (median age 85 years [IQR 81; 89]) of an assisted living facility. Among participants never infected by SARS-CoV-2, the mean serum IgG levels against RBD (2025 BAU/ml), 99 days after the fourth vaccine, was as high as 76 days after the third vaccine (1987 BAU/ml), and significantly higher (p = 0.030) when the latter were corrected for elapsed time. Neutralizing antibody levels against the historical Wuhan strain were significantly higher (Mean 1046 vs 1573; p = 0.002) and broader (against Omicron) (Mean 170 vs 375; p = 0.018), following the fourth vaccine. The six individuals with an Omicron breakthrough infection mounted strong immune responses for anti-RBD and neutralizing antibodies against the Omicron variant indicating that the fourth vaccine dose did not prevent a specific adaptation of the immune response. These findings point out the value of continued vaccine boosting in the elderly population.

Routine Upper Gastrointestinal Fluoroscopy Before Laparoscopic Sleeve Gastrectomy: Is It Necessary?

BACKGROUND: Controversy exists regarding the clinical utility of routine preoperative upper gastrointestinal (GI) fluoroscopy in morbid obese patients undergoing laparoscopic sleeve gastrectomy (LSG). The aim of our study was to determine the efficacy of these studies in detecting hiatal hernias (HH). METHODS: The institution's prospectively maintained, IRB-approved database was retrospectively queried to identify all consecutive patients who underwent LSG between 2011 and 2017. All patients underwent routine preoperative upper GI fluoroscopy. Reports from all imaging studies were retrospectively reviewed and compared to the presence of an intraoperative HH. RESULTS: During the study period, a total of 1810 patients (854 males, 956 females) underwent LSG at our institution. Mean age was 40.95 ± 13 years (range 11-75), and mean BMI was 42.8 ± 5 kg/m2 (range 30-86). The overall prevalence of HH was 11.1% (201 patients). All HHs detected were repaired. Considering the intraoperative identification of HH the gold standard for diagnosis, the sensitivity and specificity of preoperative UGI fluoroscopy for HH detection were 32% (66/201) and 94% (1512/1609), respectively. The median operative time was significantly longer when concomitant LSG and HH repair was performed compared to LSG alone (76 min vs. 55 min, p < 0.001, respectively). The foreknowledge of HH had no influence on the median operative times (77 min vs. 75 min, predicted vs. incidental, respectively, p = 1.34). HH repair did not affect the complication rate (p = 0.3). CONCLUSION: Routine preoperative upper GI fluoroscopy holds a low sensitivity for HH detection. Health policy regulators should consider omitting this exam from routine preoperative evaluation for bariatric patients.

Predictive Value of the Neutrophil/Lymphocyte Ratio in Peritoneal and/or Metastatic Disease at Staging Laparoscopy for Gastric and Esophageal Adenocarcinoma.

BACKGROUND: Despite advances in imaging techniques, peritoneal and/or metastatic disease have been identified by staging laparoscopy in up to 50 % of patients with a negative preoperative imaging. Neutrophil to lymphocyte ratio (NLR) has been recently shown as a prognostic factor in gastric and esophageal cancers. METHODS: We retrospectively reviewed the medical records of 117 patients with early gastric and lower esophagus adenocarcinoma that were referred for staging laparoscopy in the last two years in the University College Hospital, London. Complete blood count was performed preceding staging laparoscopy. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; a high NLR was defined ≥3.28. We evaluated the predictive power of a high NLR for a positive staging laparoscopy. RESULTS: The median age was 66.7 years; 87 (74.4 %) were male. Forty-four percent of the tumors were located at the gastroesophageal junction, 18 % were esophageal, and 38 % were gastric. Twenty-five (21.4 %) patients were found to have peritoneal or metastatic disease on staging laparoscopy. NLR ≥3.28 was an independent predicting factor for the discovery of peritoneal and/or metastatic disease (OR 3.9, 95 % CI: 1.54-9.86, p = 0.005). The median value of NLR was significantly higher in patients for whom the laparoscopy had discovered peritoneal or metastatic disease, than in those it had not (3.3 vs. 2.2, p = 0.011). CONCLUSION: Our findings suggest that the NLR may be reliable for predicting the presence of peritoneal or metastatic involvement on staging laparoscopy, in patients with early gastric cancer or lower esophageal cancer.

The preoperative neutrophil/lymphocyte ratio does not correlate with the 21-gene recurrence score in estrogen receptor-positive breast cancer patients.

AIMS: The aim of this study was to examine the correlation, if any, between the preoperative neutrophil/lymphocyte ratio (NLR) and the OncotypeDX™ 21-gene recurrence score (RS) in patients with early-stage estrogen receptor (ER)-positive breast cancer (BC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients diagnosed with primary ER-positive BC who were referred for the RS assay. The correlation between the preoperative NLR and the RS was analyzed. RESULTS: For the 242 patients with sufficient data for analysis, the median age at diagnosis was 59.5 years. The tumor size ranged from 0.50 to 5.50 cm, with a mean size of 1.8 cm; 73.2% of the tumors were < 2 cm in size. Most of the tumors (66.3%) were of grade 2; the rest was nearly equally divided between grades 1 and 3. The test results for the progesterone receptor (PR) were positive in 86.6% of the cases. Lymph node metastases were present in 22.3% of the patients. The median RS was 18 (range 0-60) and the mean NLR value was 2.11 (range 0.49-7.49). We found no significant correlation between the NLR and the RS. CONCLUSION: Our data suggest that the preoperative NLR does not predict the 21-gene RS in patients with early-stage hormone-sensitive BC.

Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: retrospective analysis of a single institution experience.

The aim of the present retrospective study was to evaluate the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer (CRPC) and to identify predicting factors of response to DES. Patients treated with DES during the castration-resistant phase following the failure of prior treatment with LH-RH analogs during the castration-sensitive phase were retrieved from a prostate cancer database of our institution. Patients were treated with a daily dose of DES of 1-4 mg (mean, 2.6 mg) and anticoagulants for thromboembolic prophylaxis until disease progression. We analyzed their medical records, biochemical prostate-specific antigen (PSA) response and time to disease progression (TDP). Disease response and progression were identified according to the PCWG2 criteria. Patient data were examined using Kaplan-Meier survival analysis and statistical correlation tests with intra-patient comparison of the LH-RH and DES treatment phases. Forty-three DES-treated CRPC patients were found in our database through July 2011. The median age was 66 years. Sixty-three percent of the patients achieved a ≥50% decline in their serum PSA levels during DES therapy. Median TDP was 20.4 months for LH-RH analog treatment in the castration-sensitive phase, and 7.1 months for DES treatment in the castration-resistant phase. Durable responses (>1 year) were observed in 31% of the patients. Median overall survival was 57 months from the start of the DES therapy. There was no significant correlation between the TDP under LH-RH analogs and under DES therapy among the 38 patients eligible for correlation analysis. However, the magnitudes of serum PSA responses under DES and LH-RH analogs were significantly correlated with each other, and with the TDP under DES therapy. There were no treatment-related deaths. Four patients (9%) developed thromboembolic complications while under treatment, some of which appeared to be related to a discontinuation of thromboprophylaxis. In conclusion, DES confers substantial clinical benefit in the treatment of CRPC, with a relatively good safety profile when administered with thromboprophylaxis. The use of DES may be effective in CRPC, irrespective of the length of the hormone-sensitive period with LH-RH treatment. The magnitude of PSA response to previous treatment with LH-RH analogs, as well as to DES, was predictive of the duration of response to DES.

[Intravenous vinorelbine as first line chemotherapy in patients with castration-resistant prostate cancer].

BACKGROUND: Docetaxel-based chemotherapy remains the treatment of choice in castration-resistant prostate cancer (CRPC). Generally, elderly patients poorly tolerate these drugs. Vinorelbine has a favolable toxicity profile and may be useful in elderly or unfit patients with castration-resistant prostate cancer. PURPOSE: The aim of this retrospective analysis was to evaluate the efficacy and safety of vinorelbine in patients with CRPC. PATIENTS AND METHODS: We analyzed the medical records of patients with CRPC treated in our institution with intravenous vinorelbine as first line chemotherapy. RESULTS: A total of 25 patients were assessable for efficacy. The median age was 73 years (range, 51-87 years); 9 out of 25 patients (36%) had a > 50% reduction in PSA levels from baseline. Mean progression-free survival was 7.2 months. Mean overall survival was 20.7 months. Mean overall survival for 11 patients treated with second-line taxane-based chemotherapy was 27.5 months compared to 16.8 months for patients who did not receive second-line chemotherapy. Treatment was generally well tolerated. CONCLUSION: On the basis of this small retrospective survey, we conclude that intravenous vinorelbine seems to be a therapeutic option in elderly or unfit patients with CRPC.

Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin.

AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma (ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years (range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve (AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were re-evaluated and responses to therapy based on computer tomography (CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS (V19). RESULTS: A median of 10 cycles (range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.