T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer

Purpose: Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown. Experimental Design: Therefore, we conducted a neoadjuvant, randomized study to quantify the immunologic effects of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy. Results: Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8+ T cell infiltration and PD-L1 expression as compared to a cohort of untreated, matched controls. However, the CD8+ T cell infiltrate was accompanied by a proportional increase in regulatory T cells (Treg), suggesting that adaptive Treg resistance may dampen the immunogenicity of ADT. Although Cy/GVAX followed by degarelix was associated with a modest improvement in time-to-PSA progression and time-to-next treatment as well as an increase in PD-L1, there was no difference in the CD8 T-cell infiltrate as compared to degarelix alone. Gene expression profiling demonstrated that CHIT1, a macrophage marker, was differentially upregulated with Cy/GVAX plus degarelix compared to degarelix alone. Conclusions: Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8+ T cells and Tregs, supports the development of regimens combining ADT with Treg-depleting agents in the treatment of prostate cancer

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Pentoxifylline and electromagnetic field improved bone fracture healing in rats

Yusuf Atalay,1 Nedim Gunes,2 Mehmet Dervis Guner,3 Veysi Akpolat,4 Mustafa Salih Celik,4 Rezzan Guner21Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Afyon Kocatepe University, Afyonkarahisar, 2Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Dicle University, Diyarbakir, 3Department of Orthopedics, Medicana Hospitals, Ankara, 4Department of Biophysics, Faculty of Medicine, Dicle University, Diyarbakir, TurkeyBackground: The aim of this study was to evaluate the effects of a phosphodiesterase inhibitor pentoxifylline (PTX), electromagnetic fields (EMFs), and a mixture of both materials on bone fracture healing in a rat model.Materials and methods: Eighty male Wistar rats were randomly divided into four groups: Group A, femur fracture model with no treatment; Group B, femur fracture model treated with PTX 50 mg/kg/day intraperitoneal injection; Group C, femur fracture model treated with EMF 1.5±0.2 Mt/50 Hz/6 hours/day; and Group D, femur fracture model treated with PTX 50 mg/kg/day intraperitoneal injection and EMF 1.5±0.2 Mt/50 Hz/6 hours/day.Results: Bone fracture healing was significantly better in Group B and Group C compared to Group A (P<0.05), but Group D did not show better bone fracture healing than Group A (P>0.05).Conclusion: It can be concluded that both a specific EMF and PTX had a positive effect on bone fracture healing but when used in combination, may not be beneficial.Keywords: bones, electromagnetic fields, fracture healing, phosphodiesterase inhibitor, pentoxifylline, rat

Andiferansiye Bağ Doku Hastalıklı Olguda Gluteal Kalsinozis: Cerrahi Rezeksiyonu Yapılmış Dev Lezyon

Calcinosis frequently accompanies rheumatologic diseases and mostly occurs after trauma, due to structural damage, hypovascularity, and tissue hypoxia. Calcinosis may be seen in a localized area or it may be widespread, causing muscle atrophy, joint contractures, and skin ulceration. Herein, we report a patient with localized form of calcinosis that occured without history of trauma and the patient also has a diagnosis of undifferentiated connective tissue disease. Turk J Phys Med Rehab 2011;57 Suppl 2: 358-60.Wo

Cyanoacrylate Associated Foreign Body Granulomatous Gastritis: A Report Of Three Cases

Granulomas are rarely seen in gastric biopsies mostly as an involvement of granulomatous diseases like sarcoidosis, Crohn's disease, infections, neoplasms, and vasculitis. Here, we claim cyanoacrylate as a foreign body type granuloma-causing agent in the stomach after vascular embolisation. We present cyanoacrylate associated gastric changes of three cases: two endoscopic biopsies and one gastric resection. In two cases, cyanoacrylate associated ulcers and granulomatous inflammation were observed in gastric mucosal biopsies following endoscopic examination after 7 months and 6 years of the glue injections, respectively. In the third case, the cyanoacrylate injection was performed 2 months prior to the surgery. Then the patient underwent distal pancreatectomy for pancreatic adenocarcinoma and during the operation a gastric mass was resected with a suspicion of tumoral infiltration. These three cases demonstrated that glue exposure causes active chronic inflammation with foreign body type granulomas, mucosal ulceration, and bleeding in the gastric mucosa. Even further, it can induce mass formation in the injection sites.PubMe

The Associations Between Lung Ultrasonography Scores in the First Day of Life and Clinical Outcomes

Objectives To investigate the role of lung ultrasonography (LU) in predicting noninvasive ventilation (NIV) failure and the relationship between lung ultrasonography scores (LUS) with clinical outcomes in neonatal respiratory failure (NRF)

Undifferentiated Embryonal Sarcoma Of The Liver In An Adult Patient

PubMe

Unusual presentation of a cutaneous malignancy: Giant merkel cell carcinoma with intra-abdominal metastasis

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy with uncertain histogenesis. Here, we present an unusual presentation of giant MCC of the skin with concomitant intra-abdominal metastasis to pancreas. A 53-year-old man was admitted to our clinic with a giant ulcerated mass in the gluteal region. Incisional biopsy of the mass revealed primary poorly differentiated neuroendocrine tumor of the cutaneous origin and confirmed the diagnosis of MCC. Clinically, the patient complained of abdominal discomfort and weight loss of 15 kg over the past 4 months. Intra-abdominal computerized tomographic examination demonstrated a heterogenous-appearing giant mass of the right upper quadrant invading the superior mesenteric artery and leading to obstruction of common biliary duct and a second mass (6 cm Χ 6 cm) located at the inferior pole of pancreas extending toward the duodenum. As the gluteal mass was prone to trauma and leading to massive hemorrhage, excision of the gluteal mass with 2 cm of tumor-free margin was performed. V-Y advancement flap based on the perforators of the inferior gluteal and profunda femoris artery was elevated to cover the resulting defect (22 cm Χ 17 cm). Although the patient was referred to medical oncology for further therapeutic management, he could only survive for 11 months from his initial diagnosis. We would like to emphasize that MCC has the potential to spread to unusual organs in short intervals and prompt evaluation and proper management is essential for optimal survival of these patients