Survival in patients with neuroendocrine tumors of the colon, rectum and small intestine.

BACKGROUND: Neuroendocrine neoplasms (NENs) of the colon, rectum and small intestine (SI) are increasing in incidence and prevalence. We evaluated the 5-year overall survival (OS), and cancer-specific survival (CSS). METHODS: The Surveillance, Epidemiology, and End Results (SEER) 18 registry from 2000 to 2017 was accessed to identify patients with colonic, rectal, and SI NENs. RESULTS: 46,665 patients were diagnosed with NENs of the colon (n = 10,518, 22.5%), rectum (18,063, 38.7%), and SI (18,084, 38.8%). By tumor site alone, patients with well-differentiated neuroendocrine tumors (NETs) of the rectum had improved 5-year OS (HR 0.72, 95% CI 0.68-0.77, p < 0.001). However, patients with rectal poorly-differentiated neuroendocrine carcinomas (NECs) who underwent oncologic resection had lower 5-year OS (35.1%) compared to colon (41.9%), and SI (72.5%). CONCLUSIONS: Surgical resection may improve 5-year OS for NECs of the SI and colon, except in the rectum where survival was reduced. More frequent surveillance and timely initiation of systemic therapy should be considered for rectal NECs.

Internal state effects on behavioral shifts in freely behaving praying mantises (Tenodera sinensis).

How we interact with our environment largely depends on both the external cues presented by our surroundings and the internal state from within. Internal states are the ever-changing physiological conditions that communicate the immediate survival needs and motivate the animal to behaviorally fulfill them. Satiety level constitutes such a state, and therefore has a dynamic influence on the output behaviors of an animal. In predatory insects like the praying mantis, hunting tactics, grooming, and mating have been shown to change hierarchical organization of behaviors depending on satiety. Here, we analyze behavior sequences of freely hunting praying mantises (Tenodera sinensis) to explore potential differences in sequential patterning of behavior as a correlate of satiety. First, our data supports previous work that showed starved praying mantises were not just more often attentive to prey, but also more often attentive to further prey. This was indicated by the increased time fraction spent in attentive bouts such as prey monitoring, head turns (to track prey), translations (closing the distance to the prey), and more strike attempts. With increasing satiety, praying mantises showed reduced time in these behaviors and exhibited them primarily towards close-proximity prey. Furthermore, our data demonstrates that during states of starvation, the praying mantis exhibits a stereotyped pattern of behavior that is highly motivated by prey capture. As satiety increased, the sequenced behaviors became more variable, indicating a shift away from the necessity of prey capture to more fluid presentations of behavior assembly.

Prognostic Factors in Gastrointestinal Leiomyosarcomas: An Analysis Using the Surveillance, Epidemiology, and End Results (SEER) Database.

Background Gastrointestinal leiomyosarcomas (LMSs) from intramural smooth muscle are extremely rare, with limited literature. This paper evaluates the epidemiology and survival and prognostic factors in LMSs of the gastrointestinal tract. Methods Clinical data from the Surveillance, Epidemiology and End Results (SEER) 18 registry from 2001 to 2016 with additional treatment fields were compared between primary tumor sites using the chi-squared test for categorical variables and ANOVA for continuous variables. A five-year survival rate analysis was performed for overall and cancer-specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox proportional models using the variables age group, tumor location, grade, stage, surgery, and chemotherapy. Results We identified a total of 523 patients diagnosed with LMSs of the gastrointestinal tract. The median age of diagnosis was 66 years, with no significant difference between tumor sites for age, sex, and race. The five-year overall survival was 77.3%, and the cancer-specific survival was 90.3%. In the multivariate analysis, grade and stage of tumor were the only factors significantly affecting survival in this cohort. Conclusion While surgical status significantly affected survival in the univariate analysis, when adjusted for other factors, the HR for death was not significantly different by surgical therapy. Grade 3 tumors and tumors with distant metastasis at diagnosis were associated with worse survival among these patients.

The Schistosomiasis Consortium for Operational Research and Evaluation Rapid Answers Project: Systematic Reviews and Meta-Analysis to Provide Policy Recommendations Based on Available Evidence.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research to inform global health practices related to the control and elimination of schistosomiasis. The greatest part of the SCORE investment has been in multiyear, long-term efforts, including cluster-randomized trials of gaining and sustaining control of schistosomiasis, trials on elimination of schistosomiasis, and diagnostic test development and evaluation. In the course of planning and conducting SCORE studies, critical questions were raised that could be answered relatively quickly by collecting, collating, and synthesizing existing data. Through its Rapid Answers Project (RAP), the SCORE conducted seven systematic reviews, including four associated meta-analyses, on issues related to screening for schistosomiasis, enhancing mass drug administration, treatment impacts, and the efficacy of snail control for prevention of human schistosomiasis. This article summarizes the findings of the seven RAP reports and provides links to the studies and their supporting information.

Ectopic Endometriosis Seeded to the Rectus Muscle.

Endometriosis is a pathological condition whereby endometrial glands and stroma are located outside the physiologically expected location, the uterus. A lesion is usually located in the pelvis but can also occur in the diaphragm, bowel, pleural cavity, or surgical scar. It is a benign estrogen-dependent condition. Here, we present the case of a 40-year-old woman with ectopic endometriosis.

Predatory behavior changes with satiety or increased insulin levels in the praying mantis (Tenodera sinensis).

At any given moment, behavior is controlled by a combination of external stimuli and an animal's internal state. As physiological conditions change, vastly different behaviors might result from the same stimuli. For example, the motivation to hunt and hunting strategy are influenced by satiety. Here, we describe how sensory responsiveness and motor activity of a praying mantis (Tenodera sinensis) change as the insect feeds, leading to an altered hunting strategy. We further show that these changes can be induced by injection of insulin, which likely functions as a metabotropic indicator. Praying mantises directed their attention toward real and simulated prey less often as they fed and became sated. The range of distance and azimuth at which prey was detected decreased as did pursuit of prey, while opportunistic close-range attacks persisted. Together, these sensorimotor changes are indicative of a behavioral paradigm shift from 'pursuit' to 'ambush'. A similar effect was induced in starved praying mantises injected with 0.05 ml of 200 µg ml-1 bovine insulin. These experiments showed that insulin injection into the circulating hemolymph is sufficient to decrease prey orientation as well as in prey-directed locomotor behaviors (tracking and pursuit). The effects of prey consumption and insulin injection were similarly dose dependent. These results suggest that insulin is a signal of internal, physiological conditions that can modify responses to external stimuli. A change in hunting strategy thus results from coordinated effects of a neurohormone on a set of independent sensorimotor processes and the overall activity level of the animal.

A Giant Adrenal Mass in a Super Obese Patient.

Giant pheochromocytomas (Pheo) are rare entities requiring clinical suspicion coupled with strategic diagnostic evaluation to confirm the diagnosis. The majority of cases are discovered incidentally. The diagnosis consists of biochemical evaluation and imaging study to localize the mass. Pathological examination confirms the diagnosis. The female patient in this case report presented with chest pain, palpitation of three weeks duration and was found on evaluation to have an abdominal mass concerning for pheochromocytoma. She was treated with surgical resection. The pheo measured 20.5 x 18 x 10 cm and weighed 2,582 grams. Pathological examination confirmed the diagnosis of pheochromocytoma.

Large Unilateral Adrenal Mass with Surrounding Brown Fat: A Case Report.

Pheochromocytomas are rare tumors derived from chromaffin cells located in the adrenal and extra adrenal tissues. Pheochromocytomas are diagnosed biochemically and localized using different imaging modalities. The definitive management is surgical resection. Brown adipose tissues are normally present during fetal development, with regression over time. Brown adipose tissues are thermogenic and usually located in the neck, mediastinum, and retroperitoneum. Here, we report a case of a unilateral pheochromocytoma surrounded by brown fat. The abnormal stimulation of brown fat noted on positive emission tomography scan (PET) resolved after the pheochromocytoma was resected.

Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis.

BACKGROUND: Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity. METHODOLOGY/PRINCIPAL FINDINGS: This review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome. CONCLUSION/SIGNIFICANCE: While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.

Anal Melanoma in an Elderly Woman Masquerading as Hemorrhoid.

Anal melanoma is a rare and aggressive neoplasm of the anal canal seen in the elderly population in the six or seventh decade of their lives. Presentation is usually nonspecific and diagnosis is often delayed or missed initially. The management is surgical and prognosis is poor. Here we present a case of anal melanoma in an elderly patient masquerading as hemorrhoid.

Retroperitoneal Mass Masquerading as Failure to Thrive in a 91-year-old Woman.

Failure to thrive (FTT) is a state of overall decline. Patients often present with weight loss, poor appetite, malnutrition, and decreased physical functioning. The etiology is multifactorial including chronic diseases, functional impairments, and acute illnesses. Evaluation for reversible causes is paramount, and treatment is aimed at maintaining or improving functional status. We present a case of a 91-year-old woman with a retroperitoneal mass that was found on workup for failure to thrive.

Systematic Review and Meta-analysis of the Impact of Chemical-Based Mollusciciding for Control of Schistosoma mansoni and S. haematobium Transmission.

BACKGROUND: Programs for schistosomiasis control are advancing worldwide, with many benefits noted in terms of disease reduction. Yet risk of reinfection and recurrent disease remain, even in areas with high treatment coverage. In the search for means to better prevent new Schistosoma infections, attention has returned to an older strategy for transmission control, i.e., chemical mollusciciding, to suppress intermediate host snail species responsible for S. mansoni and S. haematobium transmission. The objective of this systematic review and meta-analysis was to summarize prior experience in molluscicide-based control of Bulinus and Biomphalaria spp. snails, and estimate its impact on local human Schistosoma infection. METHODOLOGY/PRINCIPAL FINDINGS: The review was registered at inception with PROSPERO (CRD42013006869). Studies were identified by online database searches and hand searches of private archives. Eligible studies included published or unpublished mollusciciding field trials performed before January 2014 involving host snails for S. mansoni or S. haematobium, with a primary focus on the use of niclosamide. Among 63 included papers, there was large variability in terms of molluscicide dosing, and treatment intervals varied from 3-52 weeks depending on location, water source, and type of application. Among 35 studies reporting on prevalence, random effects meta-analysis indicated that, on average, odds of infection were reduced 77% (OR 0.23, CI95% 0.17, 0.31) during the course of mollusciciding, with increased impact if combined with drug therapy, and progressively greater impact over time. In 17 studies reporting local incidence, risk of new infection was reduced 64% (RR 0.36 CI95% 0.25, 0.5), but additional drug treatment did not appear to influence incidence effects. CONCLUSION/SIGNIFICANCE: While there are hurdles to implementing molluscicide control, its impact on local transmission is typically strong, albeit incomplete. Based on past experience, regular focal mollusciciding is likely to contribute significantly to the move toward elimination of schistosomiasis in high risk areas.

Neuromechanical model of praying mantis explores the role of descending commands in pre-strike pivots.

Praying mantises hunt by standing on their meso- and metathoracic legs and using them to rotate and translate (together, 'pivot') their bodies toward prey. We have developed a neuromechanical software model of the praying mantis Tenodera sinensis to use as a platform for testing postural controllers that the animal may use while hunting. Previous results showed that a feedforward model was insufficient for capturing the diversity of posture observed in the animal (Szczecinski et al 2014 Biomimetic and Biohybrid Syst. 3 296-307). Therefore we have expanded upon this model to make a flexible controller with feedback that more closely mimics the animal. The controller actuates 24 joints in the legs of a dynamical model to orient the head and translate the thorax toward prey. It is controlled by a simulation of nonspiking neurons assembled as a highly simplified version of networks that may exist in the mantid central complex and thoracic ganglia. Because of the distributed nature of these networks, we hypothesize that descending commands that orient the mantis toward prey may be simple direction-of-intent signals, which are turned into motor commands by the structure of low-level networks in the thoracic ganglia. We verify this through a series of experiments with the model. It captures the speed and range of mantid pivots as reported in other work (Yamawaki et al 2011 J. Insect Physiol. 57 1010-6). It is capable of pivoting toward prey from a variety of initial postures, as seen in the animal. Finally, we compare the model's joint kinematics during pivots to preliminary 3D kinematics collected from Tenodera.

Antimicrobial susceptibility and antibiotic resistance gene transfer analysis of foodborne, clinical, and environmental Listeria spp. isolates including Listeria monocytogenes.

The aims of this study were to assess antibiotic resistance pheno- and genotypes in foodborne, clinical, and environmental Listeria isolates, as well as to elucidate the horizontal gene transfer potential of detected resistance genes. A small fraction of in total 524 Listeria spp. isolates (3.1%) displayed acquired antibiotic resistance mainly to tetracycline (n = 11), but also to clindamycin (n = 4) and trimethoprim (n = 3), which was genotypically confirmed. In two cases, a tetracycline resistance phenotype was observed together with a trimethoprim resistance phenotype, namely in a clinical L. monocytogenes strain and in a foodborne L. innocua isolate. Depending on the applied guidelines, a differing number of isolates (n = 2 or n = 20) showed values for ampicillin that are on the edge between intermediate susceptibility and resistance. Transferability of the antibiotic resistance genes from the Listeria donors, elucidated in vitro by filter matings, was demonstrated for genes located on transposons of the Tn916 family and for an unknown clindamycin resistance determinant. Transfer rates of up to 10(-5) transconjugants per donor were obtained with a L. monocytogenes recipient and up to 10(-7) with an Enterococcus faecalis recipient, respectively. Although the prevalence of acquired antibiotic resistance in Listeria isolates from this study was rather low, the transferability of these resistances enables further spread in the future. This endorses the importance of surveillance of L. monocytogenes and other Listeria spp. in terms of antibiotic susceptibility.

Meta-analysis of urine heme dipstick diagnosis of Schistosoma haematobium infection, including low-prevalence and previously-treated populations.

BACKGROUND: Urogenital schistosomiasis remains highly endemic in Africa. Current control is based on drug administration, targeted either to school-age children or to high-risk communities at-large. Urine dipsticks for detection of microhematuria offer an inexpensive means for estimating infection prevalence. However, their diagnostic performance has not been systematically evaluated after community treatment, or in areas with continuing low prevalence. The objective of the present study was to perform meta-analysis of dipstick accuracy for S. haematobium infection in endemic regions, with special attention to performance where infection intensity or prevalence was low. METHODOLOGY/PRINCIPAL FINDINGS: This review was registered at inception with PROSPERO (CRD42012002165). Included studies were identified by computerized search of online databases and hand search of bibliographies and existing study archives. Eligible studies included published or unpublished population surveys irrespective of date, location, or language that compared dipstick diagnosis of S. haematobium infection to standard egg-count parasitology. For 95 included surveys, variation in dipstick sensitivity and specificity were evaluated according to study size, age- and sex-specific participation, region, local prevalence, treatment status, and other factors potentially affecting test performance. Independent of prevalence, accuracy was greater in surveys of school-age children (vs. adults), whereas performance was less good in North Africa, as compared to other regions. By hierarchical ROC analysis, overall dipstick sensitivity and specificity for detection of egg-positive urine were estimated at 81% and 89%, respectively. Sensitivity was lower among treated populations (72%) and in population subgroups having lower intensity infection (65%). When the insensitivity of egg count testing was considered (and diagnosis inferred instead from combined hematuria and egg-count findings), overall dipstick sensitivity/specificity were 82%/97%, with significantly better sensitivity (92%) in high prevalence settings. CONCLUSIONS/SIGNIFICANCE: This analysis suggests that dipsticks will continue to serve as very useful adjuncts for monitoring community prevalence following implementation of population-based control of urogenital schistosomiasis.

pDB2011, a 7.6 kb multidrug resistance plasmid from Listeria innocua replicating in Gram-positive and Gram-negative hosts.

pDB2011, a multidrug resistance plasmid isolated from the foodborne Listeria innocua strain TTS-2011 was sequenced and characterized. Sequence analysis revealed that pDB2011 had a length of 7641 bp and contained seven coding DNA sequences of which two were annotated as replication proteins, one as a recombination/mobilization protein and one as a transposase. Furthermore, pDB2011 harbored the trimethoprim, spectinomycin and macrolide-lincosamide-streptogramin B resistance genes dfrD, spc and erm(A), respectively. However, pDB2011 was only associated with trimethoprim and spectinomycin resistance phenotypes and not with phenotypic resistance to erythromycin. A region of the plasmid encoding the resistance genes spc and erm(A) plus the transposase was highly similar to Staphylococcus aureus transposon Tn554. The dfrD gene was 100% identical to dfrD found in a number of Listeria monocytogenes isolates. Additionally, assessment of the potential host range of pDB2011 revealed that the plasmid was able to replicate in Lactococcus lactis subsp. cremoris MG1363 as well as in Escherichia coli MC1061 and DH5α. This study reports the first multidrug resistance plasmid in L. innocua. A large potential for dissemination of pDB2011 is indicated by its host range of both Gram-positive and Gram-negative bacteria.

Tn6198, a novel transposon containing the trimethoprim resistance gene dfrG embedded into a Tn916 element in Listeria monocytogenes.

OBJECTIVES: To characterize Tn6198, a novel conjugative transposon from the clinical Listeria monocytogenes strain TTH-2007, which contains the tetracycline and trimethoprim resistance genes tet(M) and dfrG, respectively, and to assess its transferability in vitro and in situ. METHODS: The complete sequence of Tn6198 was determined using a primer walking strategy. Horizontal gene transfer studies were performed by filter matings, as well as on the surface of smear-ripened cheese and smoked salmon. The presence of Tn916-like circular intermediates was determined by PCR. Antibiotic resistance was determined by the broth microdilution method and microarray hybridization. RESULTS: Sequencing of Tn6198 revealed that a 3.3 kb fragment containing dfrG was integrated between open reading frames 23 and 24 of Tn916. Furthermore, an additional copy of Tn916 was present in L. monocytogenes TTH-2007. Both elements were transferred simultaneously and separately in vitro to recipients L. monocytogenes 10403S and Enterococcus faecalis JH2-2 by conjugation, resulting in either tetracycline- and trimethoprim-resistant or solely tetracycline-resistant transconjugants. On the surface of cheese and salmon, only L. monocytogenes 10403S transconjugants were detected. CONCLUSIONS: This study reports the first Tn916-like element associated with a trimethoprim resistance gene, as well as the first fully characterized transposon conferring multidrug resistance in L. monocytogenes. This is of concern, as trimethoprim is administered to listeriosis patients with ß-lactam allergy and as Tn6198 has a large potential for dissemination, indicated by both intra-species and inter-genus transfer.

Listeria fleischmannii sp. nov., isolated from cheese.

A study was performed on three isolates (LU2006-1(T), LU2006-2 and LU2006-3), which were sampled independently from cheese in western Switzerland in 2006, as well as a fourth isolate (A11-3426), which was detected in 2011, using a polyphasic approach. The isolates could all be assigned to the genus Listeria but not to any known species. Phenotypic and chemotaxonomic data were compatible with the genus Listeria and phylogenetic analysis based on 16S rRNA gene sequences confirmed that the closest relationships were with members of this genus. However, DNA-DNA hybridization demonstrated that the isolates did not belong to any currently described species. Cell-wall-binding domains of Listeria monocytogenes bacteriophage endolysins were able to attach to the isolates, confirming their tight relatedness to the genus Listeria. Although PCR targeting the central portion of the flagellin gene flaA was positive, motility was not observed. The four isolates could not be discriminated by Fourier transform infrared spectroscopy or pulsed-field gel electrophoresis. This suggests that they represent a single species, which seems to be adapted to the environment in a cheese-ripening cellar as it was re-isolated from the same type of Swiss cheese after more than 5 years. Conjugation experiments demonstrated that the isolates harbour a transferable resistance to clindamycin. The isolates did not exhibit haemolysis or show any indication of human pathogenicity or virulence. The four isolates are affiliated with the genus Listeria but can be differentiated from all described members of the genus Listeria and therefore they merit being classified as representatives of a novel species, for which we propose the name Listeria fleischmannii sp. nov.; the type strain is LU2006-1(T) ( = DSM 24998(T)  = LMG 26584(T)).

Gallbladder neurofibroma presenting as chronic epigastric pain - Case report and review of the literature.

CONTEXT: Benign nonepithelial neoplasms of the gallbladder are unusual. The majority of gallbladder neurofibromas are found incidentally in the gallbladder specimens following cholecystectomy. There have been only few reports in the literature describing this rare entity. In this study we report a case of gallbladder neurofibroma presenting as chronic epigastric pain in a young patient. CASE REPORT: A thirty two year old otherwise healthy man presented to our clinic with chronic epigastric pain symptom after eating. Physical examination, laboratory and radiologic workups were unremarkable for signs of biliary tract diseases. Past medical and surgical histories were significant only for neurofibromatosis type I. Due to persistent symptomatology, the patient was taken to the operating room for a diagnostic laparoscopy followed by laparoscopic cholecystectomy. Open conversion was necessitated because of the presence of a gallbladder mass preventing safe anatomic dissection. Surgical pathology revealed plexiform neurofibroma with noninflamed gallbladder. The postoperative course was unremarkable and the patient was pain free at 3 weeks postoperatively. CONCLUSIONS: Benign neoplasms such as gallbladder neurofibroma should be included in the differential diagnosis for chronic epigastric pain symptom in a young otherwise healthy patient with neurofibromatosis. Diagnostic laparoscopy should be considered in an individual presenting with this condition.