PD1 ligand functionality a biomarker of response to anti PD1 treatment in patients with HNSCC.

Therapies targeting the PD-1/PD-L1 pathway have transformed head and neck squamous cell carcinoma (HNSCC) treatment. However, predicting the response to anti-PD-1 therapy remains a clinical challenge. This study evaluated the functional binding of PD-1 ligands in 29 HNSCC patients and compared it to the standard PD-L1 Combined Positive Score (CPS). The assessment of PD-1 ligands' functionality advances the current ability to predict the response of HNSCC patients to anti-PD-1 therapy.

Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model.

INTRODUCTION: Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model. METHODS: Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume. RESULTS: In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect. CONCLUSION: Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.

Mini-HoLEP (MILEP) vs HoLEP: a propensity score-matched analysis.

BACKGROUND AND PURPOSE: Minimal invasiveness improves outcome in many surgical fields including urology. We aimed to assess intraoperative performance and clinical outcome of miniaturized holmium laser enucleation of prostate (MiLEP) (22FR). METHODS: We ran a propensity score-matched analysis among all consecutive laser enucleations of prostate performed between 9/2022 and 2/2023. It resulted in two matched comparison groups: MiLEP 22 FR (n = 40) and holmium laser enucleation of prostate (HoLEP 26 Fr) (n = 40). Statistical analysis was performed. RESULTS: MiLEP was associated with significantly less intraoperative irrigation (20.5 L vs 15 L, p = 0.002E-3), less decrease in body core temperature (0.6°C vs 0.1°C, p = 0.003E-5), and less need for meatal dilation (25% vs 78%, p = 0.01E-3). These parameters were identified as being independent in the multivariate analysis. There was a trend toward less and a shorter period of postoperative stress incontinence (SI) for the MiLEP group compared to the HoLEP group: 15% and 42% (p = 0.01) at 1 month, 8% and 14% (p = 0.07) at 2 months, and 0 and 0.3% (p = 1) at 3 months, respectively. There were no differences in prostatic enucleation effectiveness, operative time, hospital stay, complications, and improvement in the international prostate symptom score and quality of life score. CONCLUSIONS: MiLEP is feasible and provides better maintenance of body core temperature, reduction in amount of fluid irrigation, and decrease in need for meatal dilation without affecting effectiveness in comparison with HoLEP. MiLEP may reduce early postoperative stress incontinence, thereby shortening the recovery period.

En bloc holmium laser enucleation of prostate in octogenarians and nonagenarians: clinical characteristics and outcome.

Extended longevity leads to greater numbers of elderly patients with benign prostatic hyperplasia (BPH) who seek surgical solutions. We assessed the clinical characteristics and outcomes of octogenarians and nonagenarians with BPH who underwent en bloc holmium laser enucleation of prostate (HoLEP). Retrospective cohort of all consecutive HoLEP patients treated in our medical center between January 2020 and January 2023. Cohort was divided into group aged < 80 years (n = 290) and group aged ≥ 80 years (n = 77). Their demographics, presentations, indications, and outcomes were compared. Octogenarians and nonagenarians had higher rates of indwelling catheters (p = 0.00001), chronic retention (p = 0.00006), larger prostates (p = 0.03), higher American Anesthesiology Association scores (p = 0.000001), and more antiplatelet medications (p = 0.0003) at presentation. They had longer operations (median 115 vs 90 min, respectively, p = 0.0008), longer hospital stay (median 2 vs 1 day, p = 0.01E-7), a higher complication rate (17% vs 7%, p = 0.02), and a higher transitory urinary incontinence (TUI) rate (54% vs 9%, p = 0.00001). TUI was more prevalent in the older group with indwelling catheters (61% vs, 13%, p = 0.00001). The functional outcome was similar for both age groups, and all patients could void spontaneously after the procedure. En-bloc HoLEP improves urinary symptoms and quality of life in patients ≥ 80 years of age despite larger prostates, more comorbidities, and higher complications rate, compared to younger men. HoLEP bestows a significant improvement in urologic quality of life regardless of age.

Can lymphocytes serve as a predictor of response to preoperative chemoradiation therapy for locally advanced rectal cancer?

Introduction: The aim of this study is to identify factors that may predict the response of locally advanced rectal cancer tumors (LARC) to neoadjuvant chemoradiotherapy (CRT) and to evaluate the effect of circulating lymphocytes on pathological tumor response. Methods: This retrospective study included neoadjuvant CRT-treated, LARC-diagnosed patients at the Rambam Health Care Campus in Haifa, Israel. CHAID analysis, t-test, χ2 test, and ROC curve analyses were performed to explore the association between pathological complete response (pCR) and several factors including patient demographics, tumor characteristics, type of treatment, and levels of circulating lymphocytes measured on a weekly basis. Results: Out of 198 patients enrolled in the study, pCR was achieved in 50 patients (25%). ROC curve and CHAID analyses showed that absolute lymphopenia was significantly associated with lower pCR rates (p=0.046 and p=0.001, respectively). Other factors that were found to have a significant impact were radiation therapy type (p=0.033) and tumor distance from the anal verge (p= 0.041). Conclusion: An absolute decrease in the level of circulating lymphocytes during preoperative CRT to LARC is associated with poorer tumor response to treatment and thus may serve as a predictive biomarker for treatment resistance.

First-line programmed death-1 inhibitor treatment for locoregionally advanced or metastatic cutaneous squamous cell carcinoma - A real-world experience from Israel.

Objective: Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. It is usually treated surgically, with very high cure rates. However, in 3%-7% of cases, cSCC metastasizes to lymph nodes or distant organs. Many of the affected patients are elderly with comorbidities who are not candidates for standard-of-care curative-intent treatment with surgery and/or radio-/chemotherapy. Immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) pathways, have recently emerged as a potent therapeutic option. The present report presents the Israeli experience with PD-1 inhibitors for the treatment of loco-regionally advanced or metastatic cSCC in a diverse and elderly population, with or without the addition of radiotherapy. Material and methods: The databases of two university medical centers were retrospectively searched for patients with cSCC treated with the PD-1 inhibitors cemiplimab or pembrolizumab between January 2019 and May 2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed. Results: The cohort included 102 patients of a median age 78.5 years. Evaluable response data were available for 93. The overall response rate was 80.6%: complete response in 42 patients (45.2%) and partial response in 33 (35.5%). Stable disease was recorded in 7 (7.5%) and progressive disease in 11 (11.8%). Median progression-free survival was 29.5 months. Radiotherapy was administered to the target lesion during PD-1 treatment in 22.5% of patients. mPFS was not significantly different in patients who treated with RT than patients how did not (NR vs 18.4 months, HR=0.93, 95%CI: 0.39 - 2.17, p<0.859). Any-grade toxicity was recorded in 57 patients (55%), including grade _3 in 25, of whom 5 (5% of cohort) died. Compared to toxicity-free patients, patients with drug toxicity had better progression-free survival (18.4 months vs not reached, HR=0.33, 95% CI: 0.13-0.82, p=0.012) and higher overall response rate (87% vs 71.8%, p=0.06). Conclusion: This retrospective real-world study showed that PD-1 inhibitors were effective in the treatment of locally advanced or metastatic cSCC and appeared to be amenable for use in elderly or fragile patients with comorbidities. However, the high toxicity warrants consideration against other modalities. Induction or consolidation radiotherapy may improve the results. These findings need to be corroborated in a prospective trial.

Case series report: radiation-induced oropharyngeal carcinoma.

The incidence of radiation-induced secondary primary tumors (SPTs) is estimated to be between 1 and 20%. The oropharynx is not a common site for postradiotherapy head and neck SPTs. We describe the cases of eight patients, each with an SPT of the oropharynx. These developed after a long median latency of 17.7 years with each receiving two-dimensional radiation therapy and delivery of at least 5000 cGy per pharynx, except for one who was treated with IMRT. Tumor histological commonalities revealed squamous cell carcinoma p16 negative staining, local invasion, and limited lymphatic spread, with posterior wall of the oropharynx and the base of the tongue being the most common locations. Limited and challenging treatment options have been reported such as surgery, reirradiation, or clinical trials. Radiation-induced SP oropharyngeal carcinoma has unique clinical and pathological features. Patients with this disease have limited treatment options, which should be discussed in a multidisciplinary tumor board meeting. For this population, lifelong follow-up may help in early diagnosis and improve outcomes.

The evolving treatment paradigm of locally advanced rectal cancer: a narrative review.

Background and Objective: Surgery is still considered the mainstay of treatment of locally advanced rectal cancer (LARC). Nevertheless, "curable" disease may still pose a great risk for both local and distant relapses. Since the early eighties of the past century, we have witnessed mounting evidence supporting the multi-modality approach to tackle this disease effectively. The multi-modality approach is variable between different positive trials. In this review, we discuss the treatment evolution of LARC, highlighting the key differences between the different contemporary strategies utilized. Based on current evidence, we sought to define distinct patient subgroups and to propose a treatment algorithm that best fits patient's risk. Methods: We conducted a literature search through PubMed and Google scholar. Eligible papers were phase 2/3 trials [in organ preservation (OP), observational and retrospective studies were also acceptable] published in English. We used keywords such as "locally advanced rectal cancer", "perioperative therapy in rectal cancer", "short course radiotherapy", "chemoradiation in rectal cancer", "interval to surgery", "Neoadjuvant therapy", "Organ preservation" and "Total neoadjuvant treatment [TNT]". Key Content and Findings: Various trials consistently demonstrated the benefit of preoperative radiotherapy in LARC, the role of adjuvant chemotherapy is controversial based on published studies, TNT was associated with a risk reduction in distant metastasis, and more reassuring evidence is accumulating regarding OP. Conclusions: The treatment landscape of LARC is rapidly changing. Clinicians should carefully tailor treatment strategy based on patient's risk.

Tyrosine kinase inhibitor treatment and long-term follow-up for metastatic malignant struma ovarii.

Metastatic malignant struma ovarii (MMSO) is a very rare disease (in the United States, less than one case in 10 million females annually). However, this incidence rate is due to a paucity of data regarding diagnosis, treatment, and follow-up. Herein, we describe the case of a 14-year-old female who presented with MMSO, which later metastasized and was followed up on for over 10 years. The patient underwent right oophorectomy surgery and was then treated with a combination of radioactive iodine followed by iodine scans to detect the absorption of radioiodine in the metastatic sites, and radiation therapy to treat skeletal lesions. She subsequently received treatment with the tyrosine kinase inhibitors (TKIs), sorafenib and then lenvatinib, as treatments for advanced disease, thereby achieving long-term disease stability. This case report, which adds to the limited data available on MMSO treatment, suggests that patients treated with a combination of radioactive iodine, radiation therapy, and TKIs can result in good responses and long-term overall survival.

Microscopic nuclei classification, segmentation, and detection with improved deep convolutional neural networks (DCNN).

BACKGROUND: Nuclei classification, segmentation, and detection from pathological images are challenging tasks due to cellular heterogeneity in the Whole Slide Images (WSI). METHODS: In this work, we propose advanced DCNN models for nuclei classification, segmentation, and detection tasks. The Densely Connected Neural Network (DCNN) and Densely Connected Recurrent Convolutional Network (DCRN) models are applied for the nuclei classification tasks. The Recurrent Residual U-Net (R2U-Net) and the R2UNet-based regression model named the University of Dayton Net (UD-Net) are applied for nuclei segmentation and detection tasks respectively. The experiments are conducted on publicly available datasets, including Routine Colon Cancer (RCC) classification and detection and the Nuclei Segmentation Challenge 2018 datasets for segmentation tasks. The experimental results were evaluated with a five-fold cross-validation method, and the average testing results are compared against the existing approaches in terms of precision, recall, Dice Coefficient (DC), Mean Squared Error (MSE), F1-score, and overall testing accuracy by calculating pixels and cell-level analysis. RESULTS: The results demonstrate around 2.6% and 1.7% higher performance in terms of F1-score for nuclei classification and detection tasks when compared to the recently published DCNN based method. Also, for nuclei segmentation, the R2U-Net shows around 91.90% average testing accuracy in terms of DC, which is around 1.54% higher than the U-Net model. CONCLUSION: The proposed methods demonstrate robustness with better quantitative and qualitative results in three different tasks for analyzing the WSI.

[ONCOLOGY CARE CHALLENGES TREATING COVID-19 CONFIRMED CANCER PATIENTS: A REVIEW AND RECOMMENDATIONS].

INTRODUCTION: The highly contagious virus, SARS-CoV-2 causing a human respiratory disease, COVID-19, imposed a global pandemic with significant short- and long-term health consequences. It has challenged the active treatment of oncology patients, having protocols that require frequent monitoring. Some patients' anxiety of the COVID-19 pandemic led to delays in treatment and impaired the effectiveness of anti-cancer therapy. Moreover, the stage migration term was coined to newly referred patients who postponed their doctor's appointment leading to late diagnosis. Prevention of COVID-19 disease among oncology patients is a priority, in order to avert morbidity, complications and mortality. In a recently published article, Waissengrin et al. compared the incidence of COVID-19 disease in oncology patients at Tel-Aviv Medical Center to the general population between March 2020 and October 2020. A lower rate of confirmed cases was demonstrated among oncology patients in comparison to the general population. This difference was attributed to the oncology patients' adherence to COVID-19 avoidance guidelines. In addition, no association was found between a specific type of cancer or oncological treatment and mortality from COVID-19. However, a significant correlation was presented between severe COVID-19 disease, old age and the presence of metastases. Waissengrin et al., support the importance of continuing the oncological care routine to avoid the devastating consequences of postponing treatments. Despite the development of a number of FDA-approved vaccines against the virus, the world is still facing challenges associated with the COVID-19 pandemic, e.g. variant B.1.617.2 ominous of yet more lockdowns due to a rapid rising wave of morbidity.

Anti-androgen for myoepithelial tumor: a potent therapy yet a potential misleader.

Myoepithelial tumor is a rare form of cancer, mainly arising from the salivary glands and extremities. Due to its rarity, no formal treatment guidelines exist. Here we report a case of a male patient diagnosed with metastatic myoepithelial tumor which was successfully treated with an androgen-receptor (AR) antagonist (bicalutamide), based on the results of molecular testing. Six years after the initiation of bicalutamide, patient was diagnosed with metastatic prostate cancer. To our knowledge, this is the first case described in literature that demonstrate the effectiveness of anti-androgens in treating myoepithelial tumor. Vigilance should be maintained when screening these patients for prostate cancer as their 'true' prostate specific antigen levels might be masked by the ongoing endocrine therapy.

Case report: ado-trastuzumab as second-line treatment in HER2 positive salivary duct carcinoma.

The objective of this report is to present the use and efficacy of ado-trastuzumab as an advanced line of therapy in salivary duct carcinoma (SDC) patient. An 84-year-old gentleman diagnosed with metastatic salivary duct tumor harboring overexpressed human epidermal growth factor receptor-2 has gone through resection surgery. The first line of treatment included initial doublet chemotherapy combined with trastuzumab, which was continued later as maintenance. PET-CT follow-up for 4 years has demonstrated no evidence of disease. However, upon recurrence, use of Ado-trastuzumab emtansine was prompted as second-line of treatment. This targeted patient-tailored therapy has accomplished a complete response. The effectiveness of ado-trastuzumab emtansine was notable within a short time period of two treatment cycles leading to full recovery. Specific agents aimed at altered oncogenes should be considered as a potential drug of choice in neoadjuvant HER2 positive SDC.

[VESICO-VAGINAL FISTULAS (VVF)].

INTRODUCTION: Vesico-vaginal fistula, is a known complication that can occur following damage to the bladder wall during pelvic surgery or prolonged birth. Prompt and accurate diagnosis and timely repair are essential for a quick solution to the problem, and a reduction in medico-legal claims. Successful treatment requires an accurate assessment of the size and the location of the fistula, determination of timing and the surgical technique. There is an approach that advocates postponing the surgery for several months until "tissue healing" subsides and some advocate immediate repair. In our department, the surgery is performed early, immediately upon diagnosis without delay. The aim of the work is to define the clinical manifestation of fistula after surgery, to analyze the factors, and to summarize the experience of an early intervention. METHODS: We reviewed the records of consecutive patients undergoing repair of urogenital fistulas at our institution. Patients with only vesico-vaginal fistulas were included. We recorded demographic characteristics, as well as surgical data, and postoperative complications were also collected. The follow-up period was at least 3 months. RESULTS: A total of 67 women with urogenital fistulas were identified, of whom 37 were only with vesico-vaginal fistulas. Iatrogenic injury, during hysterectomy was the main cause in 70.3%; 2 women were treated conservatively. A repair in the vaginal approach was performed in 31 women, and in 4 women the repair was performed in the abdominal approach, of them, two underwent urethral re-implantation simultaneously. Complications included sepsis in one case, and vaginal cuff dehiscence in another. The success rate of the repair was 92%. Recurrence occurred in 3 patients, of whom 2 had a history of previous radiation. CONCLUSIONS: A vesico-vaginal fistula can be successfully repaired by early repair, without delay, thus saving the patient considerable distress and discomfort.

Outcomes of Open Versus Arthroscopic Broström Surgery for Chronic Lateral Ankle Instability: A Systematic Review and Meta-analysis of Comparative Studies.

BACKGROUND: Nearly 20% of acute ankle sprains progress to chronic lateral ankle instability that requires surgical intervention. In recent years, there has been a growing interest in arthroscopic Broström techniques as an alternative to open surgery. PURPOSE: To review the most up-to-date evidence comparing the outcomes of open and arthroscopic Broström procedures for chronic lateral ankle instability. STUDY DESIGN: Systematic review; Level of evidence, 3. METHODS: This review was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Relevant comparative studies in English up to May 2020 were identified. The primary outcomes were (1) functional scores (Karlsson Ankle Function Score and American Orthopaedic Foot & Ankle Society [AOFAS] score) and (2) the 10-point visual analog scale (VAS) score for pain. The secondary outcomes were differences in (1) postoperative anterior drawer and talar tilt, (2) surgical time and complication rate, and (3) time to return to sports and weightbearing. RESULTS: A total of 408 patients in 8 studies met the inclusion criteria. Of these, 193 (47.3%) patients underwent open surgery, while 215 (52.7%) patients underwent arthroscopic surgery. There were significant differences between the open and arthroscopic repair groups in mean 6-month AOFAS scores (82.4 vs 92.25, respectively; mean difference [MD], 11.36; 95% CI, 0.14-2.56; I 2 = 90%; P = .03), 1-year AOFAS scores (80.05 vs 88.6; MD, -11.96; 95% CI, -21.26 to -2.76; I 2 = 82%; P = .01), 6-month VAS scores (1.7 vs 1.4; MD, -0.38; 95% CI, -0.54 to -0.21; I 2 = 78%; P < .001), and 1-year VAS scores (2.05 vs 1.45; MD, 0.31; 95% CI, 0.09-0.54; I 2 = 0%; P < .001). The mean time to weightbearing was 14.25 and 9.0 weeks in the open and arthroscopic repair groups, respectively (MD, 1.89; 95% CI, 1.24-2.54; I 2 = 99%; P < .001). There were no statistically significant differences in the remaining outcomes evaluated. CONCLUSION: While technically more demanding, arthroscopic Broström was superior to open Broström-Gould surgery in postoperative AOFAS scores, VAS pain scores, and time to return to weightbearing. The operative time, complication rate, talar tilt, and anterior drawer tests were excellent and statistically comparable. Long-term clinical trials are required before recommending arthroscopic Broström as the new gold standard.

Efficacy of the mRNA-Based BNT162b2 COVID-19 Vaccine in Patients with Solid Malignancies Treated with Anti-Neoplastic Drugs.

The BNT162b2 vaccine was shown to be highly effective in reducing the risk of COVID-19 infection in healthy individuals and patients with chronic disease. However, there are little data regarding its efficacy in patients treated for cancer. We analyzed the humoral response following vaccination with the second dose of BNT162b2 in 140 patients with solid malignancies who were receiving anti-cancer therapy at the time of vaccination and 215 participants who had not been diagnosed with cancer. Multivariate analysis was performed, followed by matching the two groups by age, gender and days from vaccination. The humoral response in the cancer patient group was significantly lower than in the non-cancer group: 20/140 seronegative (14.3%) vs. 3/215 (1.4%), p < 0.001; median IgG levels 2231 AU/mL (IQR 445-8023) vs. 4100 (IQR 2231-6774) p = 0.001 respectively. The odds ratio for negative serology results in cancer patients adjusted by age and gender was 7.35 compared to participants without cancer. This effect was observed only in chemotherapy treated patients: 17/73 seronegative (23.3%) vs. 3/215 (1.4%), p < 0.001; median IgG 1361 AU/mL vs. 4100, p < 0.001 but not in patients treated with non-chemotherapeutic drugs. Reduced immunogenicity to COVID-19 vaccine among chemotherapy-treated cancer patients, raises the need to continue exercising protective measures after vaccination in these patients.

Treatment of Rare Mutations in Patients with Lung Cancer.

Lung cancer is a worldwide prevalent malignancy. This disease has a low survival rate due to diagnosis at a late stage challenged by the involvement of metastatic sites. Non-small-cell lung cancer (NSCLC) is presented in 85% of cases. The last decade has experienced substantial advancements in scientific research, leading to a novel targeted therapeutic approach. The newly developed pharmaceutical agents are aimed towards specific mutations, detected in individual patients inflicted by lung cancer. These drugs have longer and improved response rates compared to traditional chemotherapy. Recent studies were able to identify rare mutations found in pulmonary tumors. Among the gene alterations detected were mesenchymal epithelial transition factor (MET), human epidermal growth factor 2 (HER2), B-type Raf kinase (BRAF), c-ROS proto-oncogene (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase (NTRK). Ongoing clinical trials are gaining insight onto possible first and second lines of medical treatment options intended to enable progression-free survival to lung cancer patients.

Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

BACKGROUND: This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe®) and the conventional fixed-size ice probe. MATERIALS AND METHODS: We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage. RESULTS: A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65-74 years), 7 (IQR: 6-7) and 5.9 ng/mL (IQR: 4.6-8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2-48.6 months). V-Probes® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003). CONCLUSIONS: The use of the V-Probe® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.

L-Glutaminase Synthesis by Marine Halomonas meridiana Isolated from the Red Sea and Its Efficiency against Colorectal Cancer Cell Lines.

L-glutaminase is an important anticancer agent that is used extensively worldwide by depriving cancer cells of L-glutamine. The marine bacterium, Halomonas meridian was isolated from the Red Sea and selected as the more active L-glutaminase-producing bacteria. L-glutaminase fermentation was optimized at 36 h, pH 8.0, 37 °C, and 3.0% NaCl, using glucose at 1.5% and soybean meal at 2%. The purified enzyme showed a specific activity of 36.08 U/mg, and the molecular weight was found to be 57 kDa by the SDS-PAGE analysis. The enzyme was highly active at pH 8.0 and 37 °C. The kinetics' parameters of Km and Vmax were 12.2 × 10-6 M and 121.95 µmol/mL/min, respectively, which reflects a higher affinity for its substrate. The anticancer efficiency of the enzyme showed significant toxic activity toward colorectal adenocarcinoma cells; LS 174 T (IC50 7.0 µg/mL) and HCT 116 (IC50 13.2 µg/mL). A higher incidence of cell death was observed with early apoptosis in HCT 116 than in LS 174 T, whereas late apoptosis was observed in LS 174 T more than in HCT 116. Also, the L-glutaminase induction nuclear fragmentation in HCT 116 was more than that in the LS 174T cells. This is the first report on Halomonas meridiana as an L-glutaminase producer that is used as an anti-colorectal cancer agent.