Analytical review of 664 cases of penetrating buttock trauma

A comprehensive review of data has not yet been provided as penetrating injury to the buttock is not a common condition accounting for 2-3% of all penetrating injuries. The aim of the study is to provide the as yet lacking analytical review of the literature on penetrating trauma to the buttock, with appraisal of characteristics, features, outcomes, and patterns of major injuries. Based on these results we will provide an algorithm. Using a set of terms we searched the databases Pub Med, EMBASE, Cochran, and CINAHL for articles published in English between 1970 and 2010. We analysed cumulative data from prospective and retrospective studies, and case reports. The literature search revealed 36 relevant articles containing data on 664 patients. There was no grade A evidence found. The injury population mostly consists of young males (95.4%) with a high proportion missile injury (75.9%). Bleeding was found to be the key problem which mostly occurs from internal injury and results in shock in 10%. Overall mortality is 2.9% with significant adverse impact of visceral or vascular injury and shock (P < 0.001). The major injury pattern significantly varies between shot and stab injury with small bowel, colon, or rectum injuries leading in shot wounds, whilst vascular injury leads in stab wounds (P < 0.01). Laparotomy was required in 26.9% of patients. Wound infection, sepsis or multiorgan failure, small bowel fistula, ileus, rebleeding, focal neurologic deficit, and urinary tract infection were the most common complications. Sharp differences in injury pattern endorse an algorithm for differential therapy of penetrating buttock trauma. In conclusion, penetrating buttock trauma should be regarded as a life-threatening injury with impact beyond the pelvis until proven otherwise

Histological Risk Classification Predicts Malignancy and Recurrence in Paragangliomas

Background: Mid-term outcome information in risk stratified patient cohort is needed to inform prognosis in individual patients with paragangliomas (PGL), adjuvant therapy choice and future research. The objective is to define the outcome relevance of a novel risk stratification scheme for PGLs. Design: A classification scheme for PGLs was devised and specimen were assessed for invasion capacity (infiltrative edges with broad fibrous bands, extra-adrenal extension [recording capsular, microscopic periadrenal and gross periadrenal], capsular and peritumoral vascular invasion [recording thin- and thick-walled blood vessels]), tumorigenic expansion (expansile nodules with diffuse areas, hypercellular homogenous areas, necrosis [recording multifocal and confluent subtypes]) and mitogenic activity (MFC/10HPF, presence of atypical mitotic figures). Patients were prospectively stratified as low risk or high risk (presence of at least one feature of invasive capacity and two features of tumorigenic expansion). Patients underwent systematic treatment and follow up for their PGLs in a tertiary referral center. Results: The multilevel analysis based on 78 patients identified statistically significant differences in clinical and biochemical presentation between low risk and high risk patients for gender (p<0.05), noradrenalin (4.6±8.5 vs 11.6±16.9), dopamine (0.6±0.3 vs 1.7±2.4), size of lesion (49.8±19.5 vs 89.2±45.8) and malignancy, 0% vs 21.6% (p<0.01), treatment modalities for MIBG therapy, 0% vs 40.5% (p<.0001), MVR, 0% vs 23.3% (p<.001) and lymph node dissection, 13.5% vs 40.5% (p<0.01) and distant metastases, 0% vs 21.6% (p<0.01). Disease free survival was significantly lower in HR patients 0% vs 78.4% (p=0.004). Histological risk stratification predicts DFS with AUC of 0.8 (95% CI: 0.69-0.90; p<0.01). 7/37 patients with HR had a synchronous diagnosis of malignancy based on other criteria and 4 patients suffered local recurrence. Conclusions: Stratification as low risk excluded a synchronous diagnosis of malignancy and disease recurrence of a follow-up interval of 1-75 months (median 12 months). A high-risk status is associated with high risk of malignancy and disease recurrence.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma– SIZEPASS

AimWe seek a simple and reliable tool to predict malignant behavior of pheochromocytoma and paraganglioma (PPGL).MethodsThis single-center prospective cohort study assessed size of primary PPGLs on preoperative cross-sectional imaging and prospectively scored specimens using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS). Multiplication of PASS points with maximum lesion diameter (in mm) yielded the SIZEPASS criterion. Local recurrence, metastasis or death from disease were surrogates defining malignancy.Results76 consecutive PPGL patients, whereof 58 with pheochromocytoma and 51 female, were diagnosed at a mean age of 52.0 ± 15.2 years. 11 lesions (14.5%) exhibited malignant features at a median follow-up (FU) of 49 months (range 4-172 mo). Median FU of the remaining cohort was 139 months (range 120-226 mo). SIZEPASS classified malignancy with an area under the curve (AUC) of 0.97 (95%CI 0.93-1.01; p&lt;0.0001). Across PPGL, SIZEPASS &gt;1000 outperformed all known predictors of malignancy, with sensitivity 91%, specificity 94%, and accuracy 93%, and an odds ratio of 72 fold (95%CI 9-571; P&lt;0.001). It retained an accuracy &gt;90% in cohorts defined by location (adrenal, extra-adrenal) or mutation status.ConclusionsThe SIZEPASS&gt;1000 criterion is a lesion-based, clinically available, simple and effective tool to predict malignant behavior of PPGLs independently of age, sex, location or mutation status

Urinary Steroid Profiling for the Preoperative Identification of Adrenocortical Adenomas with Regression and Myelolipomatous Changes

Background: Adrenocortical neoplasms are classically divided into adenomas (ACA) and carcinomas (ACC). Heterogeneous appearance and greater size are criteria to suggest malignancy, along with the urinary steroid profile (USP). The presence of regression and myelolipomatous changes in adenomas (ACA-RML) can contribute to confusion with ACC and its USP remains unknown. Objective: To evaluate the features of ACA-RML in comparison with other adrenocortical neoplasms. Design: We selected consecutive ACA (11), ACA-RML (7) and ACC (13) cases for which USP analysis was performed before surgery and tissue was available for histological evaluation (King's College Hospital, 2005-2012). Cases were classified according to WHO and Armed Forces Institute of Pathology criteria. USPs were obtained by gas chromatography/mass spectrometry. Total excretion of individual steroids and indices (sums and ratios chosen to reflect steroid metabolic activity) were compared between ACA-RML, ACA, and ACC. Steroids that have proved to be useful markers of ACC were also compared empirically between groups, including tetrahydro-11-deoxycortisol, pregnene3,16,20-triols, 16a- and 21-hydroxypregnenolone and tetrahydro-11-deoxycorticosterone. Results: In comparison with ACA, tumors in ACA-RML were significantly larger (8.5±2.4 vs. 3.5±1.0, P=0.002), presented in older patients and showed relatively higher incidence in males. Mitotic figure counts were significantly lower (0.39±0.04 vs. 0.93±0.11 in ACA, p=0.001) and revealed higher frequency of apoptotic cells (100% vs. 9% in ACA, p= 0.001). The USP of ACA-RML showed no diagnostic features of ACC, along with lower levels of DHA and DHA metabolites. Conclusions: ACA-RML reveals distinctive histological features, and lack of USP markers of malignancy. It is important to recognize ACA-RML because its size and heterogeneous appearance raise the possibility of ACC; in this context, USP is an important tool for a correct preoperative diagnosis. Category: Endocrine PathologyUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Simple and effective bacterial-based intratumoral cancer immunotherapy

Background We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund’s adjuvant (CFA)) in three preclinical species and in human cancer patients. Methods Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well as survival and tumor immunohistochemistry in dogs. Tumor biopsies were taken from human cancer patients on day 5 (all patients) and day 28 (some patients) of treatment and analyzed by histology. CT scans are provided from one patient. Results Significantly extended survival was observed in mouse P815 and 4T1 tumor models. Complete tumor regressions were observed in all three non-human species (6/186 (3%) of mouse mastocytomas; 3/14 (21%) of canine mastocytomas and 2/11 (18%) of equine melanomas). Evidence of systemic immune responses (regression of non-injected metastases) was also observed. Analysis of immune cells infiltrating mastocytoma tumors in mice showed that early neutrophil infiltration was predictive of treatment benefit. Analysis of the site of mastocytoma regression in dogs weeks or months after treatment demonstrated increased B and T cell infiltrates. Thus, activation of the innate immune system alone may be sufficient for regression of some injected tumors, followed by activation of the acquired immune system which can mediate regression of non-injected metastases. Finally, we report on the use of CFA in 12 human cancer patients. Treatment was well tolerated. CT scans showing tumor regression in a patient with late-stage renal cancer are provided. Conclusion Our data demonstrate that intratumoral injection of CFA has major antitumor effects in a proportion of treated animals and is safe for use in human cancer patients. Further trials in human cancer patients are therefore warranted. Our novel treatment provides a simple and inexpensive cancer immunotherapy, immediately applicable to a wide range of solid tumors, and is suitable to patients in developing countries and advanced care settings.g Canberra trial: Canberra Hospital Private Practice Fund, Janice and Ron Parker Fund. Mouse preclinical studies: Lea Chapuis Memorial Fund. Canine preclinical studies: The John and Mary Kibble Trust (grants CT22492, CT21335) and the William Peter Richards Bequest for research into veterinary pathology. CSEC, ERA, and AAA was supported by Australian Government Research Training Program Stipend Scholarships. CSEC and K-MS were supported by Max Lindemann Memorial Foundation, Miam

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c.) with keyhole limpet hemocyanin (KLH) or human papillomavirus (HPV)16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002) or 6 mg/animal poly I:C12U (p = 0.001) when compared with immunization with KLH alone. Notably, poly ICLC—but not CpG-C given at the same dose—also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell–activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01). This was paralleled by the reduced production of the homeostatic T cell–attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants for virus-specific Th1 and humoral immune responses in nonhuman primates