Pediatric renal cell carcinomas: where do they fit in the new histologic classification of renal cell carcinoma?

Genetic, immunohistochemical, and histologic data has led to the reclassification of renal cell carcinoma in the last decade. Recent studies suggest that renal cell carcinomas in children and young adults may represent a distinct group of tumors. These tumors have unique genetic findings (most commonly t(x;1)(p11:q21)), a predominantly papillary architecture, numerous calcifications, granular cytoplasm, and a possible relationship with neuroblastoma.     

Red blood cell alloimmunization and antigen matching in sickle cell disease – the African perspective

In sickle cell disease (SCD), blood transfusion facilitates improved blood and tissue oxygenation, reduces the propensity to sickling by diluting host cells, and suppresses the production of red blood cells (RBCs) containing sickle haemoglobin (HbS). Delivery of RBC transfusions to patients with SCD varies by method (simple vs. exchange) and frequency (episodic vs. chronic). However, due to the genetic differences between blood donors and recipients, repeated transfusions increase the risk of developing alloantibodies to RBC antigens. The antigens most frequently involved belong to the Rh, Kell, Kidd, Duffy, Lewis, and MNS blood group systems. Consequences of RBC alloimmunization include delays and difficulties in obtaining compatible blood for future transfusions, the occurrence of delayed haemolytic transfusion reactions (DHTRs), the hyperhaemolysis syndrome and autoimmunization. In Europe and USA, RBC alloimmunization rates ranging from 18% to 76% have been reported in SCD while other multiply transfused (OMT) patients had alloimmunization rates of 5% to 20% indicating that SCD patients are at a higher risk of developing RBC alloantibodies. To prevent alloimmunization in SCD patients, the standard practice in Europe and USA is to determine their extended RBC phenotype (ABO, Rh, Kell, Kidd, Duffy, Lewis, MNS) before commencing transfusion therapy and perform antigen matching for C, E and K antigens for patients without prior alloantibody formation. However in Africa, lower RBC alloimmunization prevalence rates of 6–10% have been reported in SCD patients and no differences were observed between SCD and OMT patients. This may be explained by the presumed high phenotypic compatibility between donors and SCD patients who were all Black Africans. Also, a low transfusion load (a median 3 U of blood were transfused) in SCD patients might have led to the poor response to alloantigenic challenge. Anti-K alloimmunization was notably rare among African SCD patients compared to anti-S. In many African countries, pre-transfusion immunohaematologic testing includes neither the detection of RBC alloimmunization nor preventive antigen matching. Most transfusion laboratories are understaffed and underequipped; they perform ABO/D typing plus room temperature saline cross-matches and do not screen for RBC alloantibodies. Hence, immunized SCD patients are not diagnosed and do not have the opportunity of receiving antigen-negative blood. Furthermore, data on the occurrence of DHTRs are lacking. Introducing pre-transfusion RBC alloantibody screening in all African countries will significantly improve the transfusion management of SCD patients. A program of limited phenotype matching for C, E and S antigens is recommended to prevent additional alloantibody formation in immunized SCD patients in Africa.     

Prognostic role of PPAR-γ and PTEN in the renal cell carcinoma

Objective: To explore association of peroxisome proliferator-activated receptor gamma (PPAR-γ) and phosphatase and tensin homolog (PTEN) expressions with prognosis of renal cell carcinoma (RCC). Methods: Our study subjects included 87 RCC tissues, 28 paracarcinoma tissues and 21 normal renal tissues. PPAR-γ and PTEN detection was conducted using immunohistochemistry staining. The association of PPAR-γ and PTEN with the clinical parameters and prognosis of RCC was analyzed. Kaplan-Meier method and Cox’s proportional hazards regression model were used for exploring the relation between variables and prognosis. Results: Among normal renal tissues, para-carcinoma tissues and renal cell carcinomas, positive PPAR-γ expression presented with a progressive tendency (P < 0.001), while positive PTEN expression a degressive tendency (P < 0.001). PPAR-γ expressions were closely related to tumor size, clinical stage and lymph node metastases (all P < 0.05). PTEN expressions were in close association with tumor size, Fuhrman grading, lymph node metastases (all P < 0.05). PPAR-γ expressions were in a negative relation with PTEN expressions (r = -0.417, P < 0.001). Negative PPAR-γ expressions confer a significantly higher overall survival rate than positive PPAR-γ expressions (P = 0.015), while negative PTEN expressions confer a significantly lower overall survival rate than positive PTEN expressions (P = 0.003). Clinical staging, Fuhrman grading, lymph node metastases, PPAR-γ and PTEN were independent prognostic factors for prognosis (all P < 0.05). Conclusion: PPAR-γ and PTEN expressions are related to the clinical parameters and prognosis of RCC and may be a biomarker for prognosis of RCC.     

Is there sugar in the Alzheimer's disease?

Epidemiological and immunohistochemical studies focus the interest on the contribution of carbohydrates in the pathophysiology of Alzheimer's disease. Diabetes mellitus increases the risk. In the extracellular (senile) plaques, which contain aggregates of amyloid proteins, and in the neurofibrillary tangles within the cytoplasm of neurons, advanced glycation end products were detected. It is discussed whether it is a cause or an effect of the Alzheimer's disease. The vascular origin of the lesions is also considered.     

Is the renal space closed?

The aim of this study is to verify the aperture or the closure of the renal space. The study is undertaken on histological sections of fetuses in the horizontal and sagittal planes. On each side, the kidney and the suprarenal gland are disposed in a space that is closed on all sides. The anterior and posterior layers of the renal fascia fuse at the upper pole of the space to become continuous with the inferior fascia of the diaphragm. Likewise, they merge at the lower pole and at the lateral border of the space to become continuous with the fasciae of the parietal muscles. At the medial border of the space, the two layers merge to continue medially with the peri-aortocaval connective tissue; they penetrate the hilum and beneath it enclose the ureter.     

Can renal oncocytoma be distinguished from chromophobe renal cell carcinoma by the presence of fibrous capsule?

The most important differential diagnosis of chromophobe renal cell carcinoma (CRCC) is renal oncocytoma. Due to overlapping morphological characteristics of renal oncocytoma and CRCC, particularly its eosinophilic variant, making a correct diagnosis can be challenging. To date, no data are available on the presence of the tumor fibrous capsule as a diagnostic feature in differentiating these tumors. The main purpose of this study was to establish the presence and compare the thickness of the tumor fibrous capsule between two tumor groups. A total of 37 tumors—18 cases of CRCC (three eosinophilic and 15 classic) and 19 cases of renal oncocytoma—were analyzed. Four slides of each tumor stained with hematoxylin and eosin were first scanned at low-power magnification (×40) to assess the presence of the capsule. If present, the capsule was measured in three different thickest areas at higher magnification (×200). The mean value of capsule thickness was calculated and taken into consideration. The capsule was present in 12 (66.7%) cases of CRCCs and in only two (10.5%) cases of renal oncocytomas. Statistical analysis showed significant difference between the presence of fibrous capsule in these two observed tumor groups (P?=?0.001). Average thickness of capsule in CRCCs was 337.7 μm, and 115.4 μm in renal oncocytomas, but the median was not statistically significant (P?=?0.198). Studies with a larger number of cases are needed to conclude if this characteristic could be a low-cost, reliable microscopic feature in differentiating between CRCC and renal oncocytoma.     

Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome.     

Underactivation of the adiponectin–adiponectin receptor 1 axis in clear cell renal cell carcinoma: implications for progression

Energy-sensing pathways, normally coordinated by 5′ AMP-activated protein kinase (AMPK), are dysregulated in renal cell carcinoma (RCC). Obesity can accentuate the pre-existing pro-tumorigenic metabolic machinery in RCC cells through its associated obesogenic hormonal milieu, characterized by lower circulating levels of adiponectin. In RCC patients, low adiponectin levels associate clinically with more aggressive disease. We investigated the adiponectin signaling pathway in RCC, focusing on adiponectin receptor 1 (AdipoR1) and associated activation of AMPK. AdipoR1 protein in RCC and normal surrounding renal tissues was determined by Western blot analysis and immunohistochemistry. Anti-tumorigenic effects of adiponectin in RCC cells in vitro were investigated via VEGF and MMP ELISA and invasion assays. Using in vivo models of RCC, the effect of AdipoR1-knockdown (shRNA) on tumor latency, growth and dissemination were determined. AdipoR1 protein was significantly reduced in clear cell RCC specimens. Adiponectin treatment inhibited VEGF, MMP-2 and MMP-9 secretion and activity and invasive and migratory capacities of RCC cells. AMPKα1-knockdown (shRNA) attenuated adiponectin’s effects. In cells stably expressing AdipoR1-specific shRNA, AMPK activation by adiponectin was significantly reduced compared to cells expressing control shRNA. In vivo, AdipoR1 knockdown increased the growth, dissemination and angiogenesis of RCC. These findings suggest that deficiencies in the entire adiponectin hormonal axis (the hormone and its receptor) result in underactivation of AMPK leading to increased angiogenic and invasive capacities of RCC. The established link between obesity and RCC can therefore be further explained by the adiponectin deficiency in obese individuals together with reduced AdipoR1 protein in RCC.     

Is Pakistan prepared for the COVID-19 epidemic? A questionnaire-based survey

COVID-19 is a pandemic that began in China in December 2019. World health organization (WHO) has expressed fears that Pakistan might emerge as the next epicenter of this pandemic. We hypothesize that at present the Pakistani masses are not prepared to face any threat of a looming epidemic. The main aim of this study was to evaluate the basic knowledge of educational and health care workers (HCWs) regarding COVID-19, its control, and prevention. Knowledge about origin, symptoms, and spread of viral infection was assessed. In this cross-sectional survey, a self-designed questionnaire was distributed among 302 HCWs including physicians (10.9%), nurses (1.32%), lab staff (1.65%), and academic individuals including faculty and students (86.42%) of different organizations. Results were analyzed using the χ² test. Obtained results validate our null hypothesis that Pakistani masses are not well aware of the COVID-19 and strategies for the prevention and control of infection. The study concluded that individuals belonging to the front-line workers and high literacy groups are not prepared for the alarming situation in the country. Effectual implementation of infection control programs should be practiced, and it depends on awareness, training, and cooperation of individuals.     

Is the incidence of Balkan endemic nephropathy decreasing?

Balkan Endemic Nephropathy (BEN) is a non-inflammatory, slowly progressing, familial, primarily tubulo-interstitial, bilateral renal disease that affects rural populations in several Balkan countries. Our study describes a time trend of the incidence of BEN in eight villages of Vratza District, Bulgaria, for the period 1965-1987, based on three various data sets. The data suggest that after the initial peak between 1967 and 1970, the incidence remained quite stable for the period 1970-1984, and declined after 1984. However, the study also demonstrates under-recording of BEN cases and less complete case identification, especially after 1979. Migration of population might also have contributed to an apparent decline in registered cases. We detected cases of BEN in villages that previously were BEN-free. We recommended a rigorous monitoring of BEN in all afflicted countries, before concluding that the incidence of BEN is decreasing.     

Are molecular features of a chromophobic cell renal cell carcinoma correlated with clinical findings?

Lipids extracted from three human renal neoplasms have been characterized by means of 13C magnetic resonance spectroscopy. The presence of free cholesterol, high levels of unsatured fatty acids, and phosphatidylcholine, and a very high fatty acids/cholesterol ratio makes the lipid profile of a rare chromophobe cell carcinoma very similar to that of an oncocytoma. On the contrary, clear cell carcinomas are mainly characterized by the presence of almost fully esterified cholesterol and by a markedly lower level of unsatured fatty acids. Since chromophobic cell carcinomas have a more favourable prognosis than clear cell carcinomas, their analogy in the lipid composition with a benign renal neoplasm could have a clinical significance. In particular, our report suggests that cholesteryl esters and high levels of unsatured fatty acids could be a marker of a poor (clear cell carcinomas) or a good (chromophobic cell carcinomas) prognosis, respectively. More in depth studies are required of the molecular composition of the neoplastic pathologies that add new knowledge, with potential clinical implications.     

Is immunosuppression therapy in renal allograft recipients teratogenic? A single-center experience

Autosomal dominant myoclonus-dystonia syndrome (MDS) is characterized by myoclonic and/or dystonic movements with onset as early as infancy. In most families, MDS is caused by mutations in the gene SGCE, which encodes epsilon -sarcoglycan and is located on chromosome 7q21. Data from several sources, including multi-generation pedigrees revealing parent-of-origin effects on MDS penetrance, suggest that SGCE is maternally imprinted. We present a 32-month-old patient with an interstitial deletion affecting chromosome 7q21, and a phenotype including myoclonus, microcephaly, short stature, dysmorphic face and language delay. We used fluorescence in situ hybridization (FISH) to estimate the size of our patient's deletion (9.0-15 Mbp) and to confirm absence of SGCE on the affected chromosome. Polymerase chain reaction (PCR) analysis of polymorphic markers in the region revealed that the paternally inherited chromosome contained the deletion, consistent with a model of maternal SGCE imprinting. Our patient is the first case of MDS caused by complete deletion of SGCE, and represents a new contiguous gene disorder. The case underscores the need to consider chromosomal deletions in patients whose phenotypes are more complex than the classic presentation of a known disease.     

Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification

Sassa N, Tsuzuki T, Fukatsu A, Majima T, Kimura T, Nishikimi T, Yoshino Y, Hattori R & Gotoh M (2012) Histopathology 61 , 620–628 Is pT3 urothelial carcinoma of the renal pelvis a homogeneous disease entity? Proposal for a new subcategory of the pT3 classification Aims: The prognosis of urothelial carcinoma of the renal pelvis (UCRP) is heterogeneous, especially in pT3 patients. The degree of tumour parenchymal invasion is not considered for pathological tumour (pT) staging. The aim of this study was to investigate whether quantitative assessment of invasion provides a better estimation of prognosis for UCRP in pT3 patients. Methods and results: We reclassified pT3 cases into two subcategories: pT3a, in which UCRP extended only into the renal medulla; and pT3b, in which UCRP extended into the renal cortex and/or in which UCRP exhibited peripelvic fat invasion. We examined our proposed pT classification and other pathological parameters, including necrosis, lymph–vascular invasion (LVI), 1973 World Health Organization (WHO) grading, WHO/International Society of Urological Pathology grading, adjuvant chemotherapy, and pathological lymph node metastasis (pN). The study included 275 patients. Among 96 patients with pT3, there was a statistically significant difference between the pT3a and pT3b subcategories in cancer‐specific survival (P < 0.001). Our proposed pT classification, as well as necrosis, LVI, 1973 WHO grading, and pN, demonstrated prognostic differences in univariate analysis, whereas in multivariate analysis, only our proposed classification (P = 0.008) and pN (P = 0.002) were statistically significant. Conclusions: The pT3b subcategories should be regarded as true pT3, having the established features of that stage, whereas pT3a has a better prognosis.     

Does e-pain plan improve management of sickle cell disease associated vaso-occlusive pain crisis? A mixed methods evaluation

PurposeThere is limited application and evaluation of health information systems in the management of vaso-occlusive pain crises in sickle cell disease (SCD) patients. This study evaluates the impact of digitization of paper-based individualized pain plans on process efficiency and care quality by examining both objective patient data and subjective clinician insights.MethodsRetrospective, before and after, mixed methods evaluation of digitization of paper documents in Children's Hospital of Pittsburgh of UPMC. Subjective perceptions are analyzed using surveys completed by 115 clinicians in emergency department (ED) and inpatient units (IP). Objective effects are evaluated using mixed models with data on 1089 ED visits collected via electronic chart review 28 months before and 22 months after the digitization.ResultsSurveys indicate that all clinicians perceived the digitization to improve the efficiency and quality of pain management. Physicians overwhelmingly preferred using the digitized plans, but only 44% of the nurses had the same response. Analysis of patient records indicates that adjusted time from analgesic order to administration was significantly reduced from 35.50 to 26.77 min (p < .05). However, time to first dose and some of the objective quality measures (time from administration to relief, relief rate, admission rate, and ED re-visit rate) were not significantly affected.DiscussionThe relatively simple intervention, high baseline performance, and limited accommodation of nurses’ perspectives may account for the marginal improvements in process efficiency and quality outcomes. Additional efforts, particularly improved communication between physicians and nurses, are needed to further enhance quality of pain management.ConclusionThis study highlights the important role of health information technology (HIT) on vaso-occlusive pain management for pediatric patients with sickle cell disease and the critical challenges in accommodating human factor considerations in implementing and evaluating HIT effects.