Grade migration and important prognostic factors in a pathology specimen for radical radiotherapy in prostate cancer patients.

The study aimed to evaluate grade migration and prognosis depending on pathologic features in patients with prostate cancer treated with radical external beam radiotherapy. The study included 139 patients with an initial Gleason score of 7 (3+4 or 4+3) i.e., Grade Group 2-3 (GG2-GG3) treated between 2008 and 2013. The clinical outcome was assessed with respect to biochemical control (BC) and biochemical disease-free survival (bDFS). After re-evaluation, the majority of patients (96 patients - 69%) were up-graded from GG2-3. Finally, there were 4 patients (3%) with grade GG1, 12 patients (9%) - GG2, 27 patients (19%) - GG3, 51 patients (37%) - GG4 and 45 patients (32%) - GG5. In 42 patients (30%) a cribriform pattern was observed. Among the analyzed factors only the GGs were important for BC (p = 0.011) and the cribriform pattern was of borderline significance (p = 0.06). The 5-year biochemical control was 100% in GG1-3 and 84% in GG4-5. The 5-year biochemical control was 81% and 93%, if cribriform or no cribriform pattern was detected, respectively. In conclusion, re-evaluation and verification of pathology specimens in accordance with contemporary rules upgraded the Gleason score in the majority of patients. The aggressive behavior of prostate cancer starts to occur from GG 4. Cribriform pattern almost tripled the biochemical failure rate.

The role of endoscopic and demographic features in the diagnosis of gastric precancerous conditions.

INTRODUCTION: The diagnosis of atrophic gastritis (AG) and intestinal metaplasia (IM) is a crucial screening and surveillance strategy for gastric adenocarcinoma. OBJECTIVES: The main objective was to assess the performance of endoscopic diagnosis of gastric precancerous conditions in a real­life scenario. PATIENTS AND METHODS: A total of 2099 gastroscopies with biopsy to evaluate gastritis performed in 3 endoscopic centers from March 2018 to October 2019 were retrospectively analyzed. Endoscopic data regarding gastritis, atrophy, and intestinal metaplasia were compared with histopathological reports. RESULTS: The endoscopic diagnosis sensitivity was 69.5% for AG and 19.4% for IM. The specificity of endoscopic detection of AG was 69.5% and of IM, 97.9%. The endoscopic detection of gastritis was a risk factor for AG and IM diagnosis (odds ratio [OR], 5.1; 95% CI, 1.9-14.1 and OR, 14.5; 95% CI, 5.9-35.8, respectively) and the patient's age was a risk factor for AG, IM, dysplasia, and advanced stage of AG (ASAG) diagnosis (OR, 1.05; 95% CI, 1.04-1.06; OR, 1.035; 95% CI, 1.03-1.04; OR, 1.04; 95% CI, 1.02-1.06; and OR, 1.05; 95% CI, 1.02-1.09, respectively). The age threshold of 45 or 40 years with endoscopically diagnosed gastritis for obtaining biopsy would result in 96.3% and 95% ASAG or dysplasia diagnosis sensitivity, and in the reduction of the number of biopsies by 20.2% and 20.5%, respectively. CONCLUSIONS: The application of the age threshold with or without an endoscopic diagnosis of gastritis could reduce the number of mapping biopsies to detect advanced stages of atrophic gastritis or dysplasia with high sensitivity.

Assessment of sheep knee joint after ACL replacement with Achilles tendon autograft and PLA-based implant.

In this study, we propose a new approach in the anterior cruciate ligament (ACL) replacement to provide stability and integration with bone tunnel. A polylactide (PLA)-based tubular implant was used to support the graft stabilization in femoral and tibial bones and to stimulate the healing process after (ACL) replacement on a sheep model. The ACL was replaced with an autologous Achilles tendon split graft. The tendon-to-bone healing in the model was analyzed after 6 and 12 weeks. Two groups of animals were compared, i.e. the group with the PLA-based implant used in the ACL replacement and the control group without the implant. The knee joints were mechanically and clinically evaluated, including the histopathology tests, to determine their stability and integrity. The results indicated that the bioresorbable PLA-based tubular implant may facilitate integration of the tendon graft with bone. Remodeling the allograft inside the implant improves the joint mobility from the first week of healing: no pathological changes were observed at the surgery site and in the animals' mobility. After 6 and 12 weeks of healing no significant changes in the mechanical parameters of the knee joint were observed, regarding the joint failure force, knee displacement, angular mobility range and joint stiffness. Relatively small values of the non-destructive tests in the knee displacement, already 6 weeks after surgery, indicated the early stabilization of the knee joint. The studies showed that the failure forces of knee joints after the ACL replacement with the PLA-based implant are lower than those of an intact joint, although their biomechanical features, including strain-at- failure, are similar. The biomechanical parameters of the knee joint were significantly improved due to the selected method of attaching the autograft ends to the femoral and tibial bone surfaces. After 12 weeks the intra-tunnel tendon-bone site with the PLA implant revealed the better tibia-femur joint mechanical stability, linear force-strain function and the decreasing strain-to-failure value, as compared to the control group.

The Concentration of CMKLR1 Expression on Clinicopathological Parameters of Colorectal Cancer: A Preliminary Study.

Background and Objectives: Colorectal cancer (CRC) is the second-most common cause of cancer-related deaths worldwide. Angiogenesis is crucial for cancer growth, infiltration of surrounding tissues, and metastasis and plays a key role in the pathogenesis of CRC. Chemerin/chemokine-like receptor 1 (CMKLR1) is one of the biochemical pathways involved in the regulation of angiogenesis in solid tumors. The aim of the study was to assess the CMKLR1 level in tumor and margin tissues of CRC in relation to histopathological parameters: microvessel density (MVD), budding, tumor-infiltrating lymphocytes (TILs), TNM scale, and grading. Materials and Methods: The study involved 43 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of CMKLR1 a commercially available enzyme-linked immunosorbent assay kit was used. For 35 cases, we performed CD34 immunostaining. The MVD, budding, and TILs were assessed using a light microscope. Results: The levels of CMKLR1 in both tumor and margin were negatively correlated with MVD and budding. CMKLR1 concentration in margin was higher in tissues with lymphocytic infiltration. Conclusions: Low vascularity and low budding are associated with higher CMKLR1 expression. CMKLR1 might play a multifunctional role in CRC pathogenesis by influencing tumor budding and peritumoral lymphocytic infiltration.

Advanced Leiomyosarcoma of the Retroperitoneal Space in a Kidney Transplant Recipient with a History of Peritoneal Dialysis: A Case Report.

BACKGROUND Leiomyosarcoma frequently occurs in patients who are on immunosuppressive therapy. It is the second most common sarcoma in this population and is often associated with Epstein-Barr virus (EBV) infection. We present a case of advanced leiomyosarcoma of the retroperitoneal space in a kidney transplant recipient and discuss additional risk factors for oncogenesis. CASE REPORT A 44-year-old woman with a history of peritoneal dialysis and kidney transplantation was diagnosed with multiple liver lesions. PET-CT scanning showed a metabolically active tumor in the left lumbar region with numerous liver focal lesions. The histological examination of the liver lesion biopsy identified advanced retroperitoneal leiomyosarcoma with a high proliferative index and liver involvement. Unexpectedly, the relation with EBV infection was not proven. The patient was treated with first-line doxorubicin, with the simultaneous reduction of immunosuppression. Owing to disease progression after 6 cycles, the patient received second-line chemotherapy based on gemcitabine and docetaxel, which was terminated owing to unacceptable toxicity, despite an observed response. Third-line trabectedin-based therapy with good tolerance and stabilization of disease after 20 months was being maintained at the time of this report. CONCLUSIONS The increased cancer mortality in solid-organ transplant recipients requires an individualized approach and increased post-transplantation screening according to additional specific cancer risk factors. A further consideration is the hypothetical relevance of long-term peritoneal membrane irritation in peritoneal dialysis patients.

Recurrence of melanoma in the scar after excised Spitz nevus in a 17-year-old child

Abstract Melanoma in childhood is rare and its diagnosis is more difficult than in adults, as it often presents histologic features overlapping with the Spitz nevus. The authors report the case of a 17-year old boy who was first diagnosed with Spitz nevus, however, the final diagnosis made after the excision of the tumor arising in the scar was changed to melanoma. The case in this present study emphasizes the importance of the differential diagnosis of skin tumors in young patients.

Composite detection rate as an upper gastrointestinal endoscopy quality measure correlating with detection of neoplasia.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is commonly used diagnostic method with no widely accepted quality measure. We assessed quality indicator-composite detection rate (CDR)-consisting of detection of at least one of the following: cervical inlet patch, gastric polyp and post-ulcer duodenal bulb deformation. The aim of the study was to validate CDR according to detection rate of upper gastrointestinal neoplasms (UGN). METHODS: It was a multicenter, prospective, observational study conducted from January 2019 to October 2019. The endoscopic reports from 2896 symptomatic patients who underwent diagnostic EGD were analyzed. The EGDs were performed in three endoscopy units located in tertiary university hospital, private outpatient clinic and local hospital. RESULTS: 64 UGNs were detected. The mean CDR was 21.9%. The CDR correlated with UGN detection rate (R = 0.49, p = 0.045). Based on CDR quartiles, operators were divided into group 1 with CDR < 10%, group 2 with CDR 10-17%, group 3 with CDR 17.1-26%, and group 4 with CDR > 26%. Detection rate of UGN was significantly higher in the group 4 in comparison to group 1 (OR 4.4; 95% CI 2.2 - 9.0). In the multivariate regression model, patient age, male gender and operator's CDR > 26% were independent risk factors of UGN detection (OR 1.03; 95% CI 1.01 - 1.05, OR 2; 95% CI 1.2 - 3.5, and OR 5.7 95% CI 1.5 - 22.3, respectively). CONCLUSIONS: The CDR is associated with the detection of upper gastrointestinal neoplasms. This parameter may be a useful quality measure of EGD to be applied in general setting.

Recurrence of melanoma in the scar after excised Spitz nevus in a 17-year-old child.

Melanoma in childhood is rare and its diagnosis is more difficult than in adults, as it often presents histologic features overlapping with the Spitz nevus. The authors report the case of a 17-year old boy who was first diagnosed with Spitz nevus, however, the final diagnosis made after the excision of the tumor arising in the scar was changed to melanoma. The case in this present study emphasizes the importance of the differential diagnosis of skin tumors in young patients.

Leydig cell ovarian tumor - clinical case description and literature review.

Leydig cell ovarian tumors constitute not only a medical problem for clinicians but also a social problem - which is why women with symptoms of hirsutism relatively quickly contact physicians for medical consultation. Leydig cell ovarian tumor is a rare sex cord-gonadal stromal tumor which constitutes less than 0.5% of ovarian tumors. These cancers appear at all ages but the majority of the cases concern women in the perimenopause. In the majority of cases (70-85%), the growth is accompanied by androgen secretion, together with virilization and hirsutism. The presence of hormonally active ovarian cancers should be suspected in cases of rapidly growing symptoms of masculinization, especially when the level of free testosterone in the blood exceeds the upper limit for the given age more than three times. In diagnosing postmenopausal hyperandrogenism, it is necessary to take into account hormonally active ovarian tumors, as well as adrenal cancers. It is important to exclude other causes of hyperandrogenism, e.g. endocrinopathies (acromegaly or hypothyroidism), or iatrogenic and idiopathic factors. In order to make the diagnosis and implement the proper treatment method faster, an interdisciplinary team of physicians specializing in endocrinology, gynecology and oncology is crucial. This paper contains a study of two cases concerning Leydig cell ovarian tumors in women of postmenopausal age with symptoms of masculinization and hirsutism.

The new method, the old problem - role of contrast-enhanced spectral mammography in the diagnosis of breast cancer among Polish women.

PURPOSE: The aim of the study was to evaluate spectral mammography (CESM) in diagnosing breast cancer, which is based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). MATERIAL AND METHODS: The study included a group of 547 women who underwent spectral mammography and histopathological verification of the lesion, previously seen in mammography and/or ultrasound. In the group of 547 women, 593 focal lesions were diagnosed. All CESM examinations were carried-out with a digital mammography device dedicated to performing dual-energy CESM acquisitions. An intravenous injection of 1.5 ml/kg of body mass of non-ionic contrast agent was performed. RESULTS: The analysis includes 593 breast lesions, in this group cancer was detected in 327 (55.14%) lesions, and in 256 (43.17%) cases benign lesions were confirmed by histopathological examination and at least 12 months of observation. The method shows differentiation of benign and malignant lesions in the breast: sensitivity of 97.86%, specificity of 59.4%, PPV - 74.76%, NPV - 95.76%. CONCLUSIONS: Spectral mammography could be an ideal method to detect breast cancer. Thanks to the high NPV (95.76%), it facilitates the exclusion of cancer in situations where pathological contrast enhancement is not observed. The unsatisfactory specificity of the study (59.4%) would not make it safe to avoid a core needle biopsy of lesions that undergo contrast enhancement.

Aggressive Angiomyxoma in an 11-Year-Old Boy - Diagnostic and Therapeutic Dilemmas: An Unusual Case Report and Review of the Literature.

Aggressive angiomyxoma (AAM) is a rare tumor with a high risk of local recurrence. Scrotal AAM mimics common pediatric pathologies including hernia or hydrocele. We present 11-year-old boy who underwent macroscopically radical excision of right scrotal AAM. The patient has been already followed up for 29 months utilizing US every 6 months and MRI every 2 years. Residual scrotal mass has been visualized in MRI 3 months after surgery however no further growth was reported. Long term follow up with reliable local imaging is mandatory.

Effects of Polylactide Copolymer Implants and Platelet-Rich Plasma on Bone Regeneration within a Large Calvarial Defect in Sheep.

The aim of this study was to verify whether L-lactide/DL-lactide copolymer 80/20 (PLDLLA) and platelet-rich plasma (PRP) trigger bone formation within critical-sized calvarial defects in adult sheep (n = 6). Two craniectomies, each ca. 3 cm in diameter, were created in each animal. The first craniectomy was protected with an inner polylactide membrane, filled with PRP-polylactide granules, and covered with outer polylactide membrane. The second control craniectomy was left untreated. The animals were euthanized at 6, 7, 17, 19, 33, and 34 weeks after surgery, and the quality and the rate of reossification were assessed histomorphometrically and microtomographically. The study demonstrated that application of implants made of PLDLLA 80/20 combined with an osteopromotive substance (e.g., PRP) may promote bone healing in large calvarial defect in sheep. These promising proof-of-concept studies need to be verified in the future on a larger cohort of animals and over a longer period of time in order to draw definitive conclusions.

Protective Effect of Polyphenol-Rich Extract from Bee Pollen in a High-Fat Diet.

We have studied a preventive effect of polyphenol-rich bee pollen ethanol extract (EEP) against histological changes in the liver and cardiac blood vessels, abnormalities of lipid profile, and the levels of oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) caused by a high-fat diet in C57BL6 mice. Supplementing the diet with EEP in the doses of 0.1 g/kg body mass (BM) and 1 g/kg BM resulted in a decrease of total cholesterol by 31% and 35%, respectively. It also decreased the level of low density lipoproteins by 67% and 90%, respectively. No differences in the levels of high density lipoprotein and triacylglycerols were observed. EEP reduced the level of ox-LDL by 33% and 47%, ADMA by 13% and 51%, ACE by 17% and 30%, as well as ANG II by 11% and 15% in a dose-dependent manner, which proves a protective effect of EEP in a high-fat diet. EEP reduces and/or prevents hepatic steatosis and degenerative changes caused by a high-fat diet in C57BL6 mice, which indicates its hepatoprotective effect. EEP used with standard feed does not disturb a normal concentration of the assayed parameters.

Serum interleukin­17 levels predict inflammatory activity in patients with autoimmune hepatitis.

INTRODUCTION    The etiology of autoimmune hepatitis (AIH) is unclear, with molecular mimicry between host and viral/drug antigens being the most plausible mechanism initiating the immune cascade that induces hepatocyte injury. Finding a serologic parameter that closely relates to the liver histology would be beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES    We studied serum interleukin (IL)-17 levels and IL­17 activators (IL­6 and transforming growth factor ß1 [TGF-ß1]) in treatment-naive and immunosuppressed patients with AIH. We also analyzed the relationships between these cytokines and histological inflammation scores. PATIENTS AND METHODS    A total of 44 patients with confirmed AIH were enrolled to the study (22 treatment-naive patients and 22 patients in clinical remission after at least 3 years of immunosuppression). Liver biopsies were performed, and the histological grading of inflammatory activity was performed by a single pathologist. The control group comprised 30 healthy age- and sex­matched subjects. Serum IL­17, IL­6, and TGF­ß1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS    Serum IL­17, IL­6, and TGF­ß1 levels were higher in treatment-naive patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively). In treatment-naive patients, serum IL­17 negatively correlated with hepatic inflammation (r = -0.63, P = 0.01). A reduced serum IL­17 concentration correlated with an increased TGF­ß1 concentration in patients in clinical remission (r = -0.51, P = 0.03). CONCLUSIONS    Serum IL­17 levels may be a useful parameter for assessing disease activity in patients with AIH.

Hepatic chemerin mRNA in morbidly obese patients with nonalcoholic fatty liver disease.

The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin concentration, and immunohistochemical staining for chemerin and and chemokine receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with metabolic and histopathological features. Chemerin mRNA was assessed by quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression with specific antibodies, while serum chemerin concentration was assessed with commercially available enzyme-linked immunosorbent assays. Serum chemerin concentration reached 874.1 ±234.6 ng/ml. There was no difference in serum chemerin levels between patients with BMI < 40 kg/m2 and ≥ 40 kg/m2. Serum chemerin concentration tended to be higher in patients with hepatocyte ballooning, greater extent of steatosis, and definite nonalcoholic steatohepatitis (NASH). Liver chemerin mRNA was observed in all included patients and was markedly, but insignificantly, higher in those with BMI ≥ 40 kg/m2, hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning, and NAFLD activity score (NAS) but seemed not to be a primary driver regulating liver necroinflammatory activity and fibrosis. The lack of association between serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not the liver is the main source of chemerin in morbidly obese women.

Vaspin mRNA levels in the liver of morbidly obese women with nonalcoholic fatty liver disease.

The aim of this study was to evaluate hepatic vaspin mRNA in morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to look for its relationships with metabolic and histopathological features. The study included 56 severely obese women who underwent intraoperative wedge liver biopsy during bariatric surgery. Hepatic vaspin mRNA was assessed by quantitative real-time PCR. Vaspin mRNA found in all included patients was markedly higher in patients with body mass index (BMI) ≥ 40 kg/m2 (4.59 ±3.09 vs. 0.44 ±0.33; p = 0.05). An evident but statistically insignificant difference in vaspin mRNA levels was observed between patients with and without hepatocyte ballooning (4.77 ±4.23 vs. 0.45 ±0.29, respectively), with and without steatosis (4.80 ±4.20 vs. 0.41 ±0.29, respectively), without and with fibrosis (0.25 ±0.80 vs. 6.23 ±7.2, respectively), and those without and with lobular inflammation (0.27 ±1.0 vs. 5.55 ±10.1, respectively). There was marked difference in vaspin mRNA between patients with simple steatosis/borderline nonalcoholic steatohepatitis (NASH) compared to those with definite NASH (0.24 ±0.96 vs. 10.5 ±10.4). Adiposity is an undoubted confounding factor influencing vaspin levels. Hepatic vaspin mRNA seems to be markedly elevated in morbidly obese patients with more advanced NAFLD and when hallmarks of NASH were observed. Pointing to non-linear mRNA levels within the NAFLD spectrum and an evident increase in patients with fibrosis and definite NASH, the detrimental action of vaspin cannot be excluded.