Digital imaging software versus the "eyeball" method in quantifying steatosis in a liver biopsy.

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.

A 52-Year-Old Man With Chest Pain and Dyspnea.

CASE PRESENTATION: A 52-year-old man came to the cardiac surgery clinic for pulmonary thromboendarterectomy (PTE) evaluation. He had initially appeared at an outside hospital 1 year earlier, with chest pain and shortness of breath. He had no known chronic conditions. A CT pulmonary angiogram (CTPA) at that time showed a filling defect at the bifurcation of the main pulmonary artery. A transthoracic echocardiogram revealed mild mitral valve regurgitation, but otherwise the results were normal. As he was hemodynamically stable and not hypoxemic, he was treated solely by anticoagulation. Despite adhering to prescribed apixaban, he developed progressive dyspnea and reduced exercise tolerance over the subsequent year. A repeat CTPA performed 12 months after the initial presentation showed a persistent filling defect at the level of the pulmonary artery bifurcation, with a new extension now completely occluding the right main pulmonary artery. A pulmonary angiogram confirmed this complete occlusion, and right heart catheterization revealed precapillary pulmonary hypertension, with a mean pulmonary artery pressure of 50 mm Hg. His anticoagulation was transitioned to enoxaparin for presumed apixaban treatment failure, and an investigation for hypercoagulable conditions was initiated. His lupus anticoagulant test result was positive, but he did not meet the criteria for antiphospholipid syndrome because he was negative for anticardiolipin and ß2-glycoprotein antibodies. Assays for antithrombin III, protein C, prothrombin gene, and factor V Leiden mutations produced normal results.

An unusual case of carcinoma with mesonephric-like features with a spindle cell component diagnosed on the Pap test of the uterine cervix: Cytomorphologic and immunophenotypic features and diagnostic pitfalls.

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the cervix, endometrium, and ovary. In contrast to mesonephric carcinomas (MC), mesonephric-like adenocarcinomas are not associated with mesonephric remnants. Both entities have a similar appearance with regards to varying histomorphology patterns, including glandular, tubular, spindled, solid, and papillary, and have a specific immunophenotype and molecular features. We present a case of a 54-year-old HPV-negative woman with a Pap test that exhibits high-grade malignancy. The cell block displayed malignant cells with positive stains for PAX8, GATA3, and TTF1 by immunohistochemistry. The diagnosis of adenocarcinoma with mesonephric like features was rendered. MLA can be challenging on the small specimens and often misinterpreted as other endometrial neoplasms. Furthermore, the accurate diagnosis carries a well-described risk of aggressive clinical behavior.

Gastric Mucosal Devitalization (GMD): Using the Porcine Model to Develop a Novel Endoscopic Bariatric Approach.

BACKGROUND AND AIMS: As the pig model has similar gastrointestinal anatomy and physiology to humans, we used pigs to create a gastric mucosal devitalization (GMD) model in preparation for clinical translation of this technique as an endoscopic bariatric therapy (EBT). The aims of this study were to determine the ablation parameters and technique for a successful, safe, and feasible large surface area GMD that produces weight loss. METHODS: We performed GMD using argon plasma coagulation (APC) in 3 phases. Phase 1 assessed the ablation energy required to accomplish selective mucosal ablation using ex vivo pig stomachs (n = 2). Phase 2 assessed the optimal percentage of mucosal surface area to be treated and was performed on 10 pigs. Phase 3 assessed feasibility, efficacy, and safety with 8 pigs randomized into GMD (n = 4) or sham (SH, n = 4) and survived for 1 month. Body weights (GMD, n = 4, SH, n = 4) were measured daily in phase 3 for 1 month, and relative body weights were calculated and analyzed using one-tailed Student's t-test. Percent body fat was compared between GMD and SH at baseline and 1 month post-GMD. RESULTS: Phase 1 identified the optimal ablation parameters (120 W) that were then used in phase 2. Phase 2 revealed a trend that was suggestive that the optimal percent surface area to ablate was similar to that which is removed at laparoscopic sleeve gastrectomy. In phase 3, GMD was performed over 70% surface area of the greater curvature of the stomach in four pigs. GMD pigs had significantly lower relative body weight increase compared to SH at 1 month (1.375 ± 0.085 vs 1.575 ± 0.047, p = 0.0435). MRI showed a significantly lower body fat mass at 1 month in GMD pigs (5.9 ± 0.4% vs 12.7 ± 2.3%, p = 0.026) compared to SH. CONCLUSIONS: GMD resulted in decreased weight gain in the GMD group as evidenced by a lower relative body weight at 1 month. GMD in an animal model appears to show promise as a potential weight loss therapy.

Phase I Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844).

PURPOSE: Epigenetic modulators improve immune checkpoint inhibitor (ICI) efficacy and increase CD8+ effector:FoxP3+ regulatory T cell ratios in preclinical models. We conducted a multicenter phase I clinical trial combining the histone deacetylase inhibitor entinostat with nivolumab ± ipilimumab in advanced solid tumors. PATIENTS AND METHODS: Patients received an entinostat run-in (5 mg, weekly × 2) prior to the addition of ICIs. Dose escalation followed a modified 3+3 design [dose level (DL)1/2: entinostat + nivolumab; DL 3/4: entinostat + nivolumab + ipilimumab]. Blood and tissue samples were collected at baseline, after entinostat run-in, and after 8 weeks of combination therapy. Primary endpoints included safety and tolerability, and the recommended phase II dose (RP2D). Secondary endpoints included antitumor activity and change in tumor CD8/FoxP3 ratio pre- and post-therapy. RESULTS: Thirty-three patients were treated across four dose levels. Treatment-related adverse events (AE) included fatigue (65%), nausea (41%), anemia (38%), diarrhea (26%), and anorexia (26%). Grade 3/4 AEs included fatigue (n = 7, 21%), anemia (n = 9, 27%), and neutropenia (n = 4, 12%). The RP2D was 3 mg entinostat weekly, 3 mg/kg every 2 weeks nivolumab, and 1 mg/kg every 6 weeks ipilimumab (max four doses). The objective response rate by RECIST 1.1 was 16%, including a complete response in triple-negative breast cancer. A statistically significant increase in CD8/FoxP3 ratio was seen following the addition of ICIs to entinostat, but not post-entinostat alone. CONCLUSIONS: The combination of entinostat with nivolumab ± ipilimumab was safe and tolerable with expected rates of immune-related AEs. Preliminary evidence of both clinical efficacy and immune modulation supports further investigation.

G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis.

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon.

LIN28B induces a differentiation program through CDX2 in colon cancer.

Most colorectal cancers (CRCs) are moderately differentiated or well differentiated, a status that is preserved even in metastatic tumors. However, the molecular mechanisms underlying CRC differentiation remain to be elucidated. Herein, we unravel a potentially novel posttranscriptional regulatory mechanism via a LIN28B/CDX2 signaling axis that plays a critical role in mediating CRC differentiation. Owing to a large number of mRNA targets, the mRNA-binding protein LIN28B has diverse functions in development, metabolism, tissue regeneration, and tumorigenesis. Our RNA-binding protein IP (RIP) assay revealed that LIN28B directly binds CDX2 mRNA, which is a pivotal homeobox transcription factor in normal intestinal epithelial cell identity and differentiation. Furthermore, LIN28B overexpression resulted in enhanced CDX2 expression to promote differentiation in subcutaneous xenograft tumors generated from CRC cells and metastatic tumor colonization through mesenchymal-epithelial transition in CRC liver metastasis mouse models. A ChIP sequence for CDX2 identified α-methylacyl-CoA racemase (AMACR) as a potentially novel transcriptional target of CDX2 in the context of LIN28B overexpression. We also found that AMACR enhanced intestinal alkaline phosphatase activity, which is known as a key component of intestinal differentiation, through the upregulation of butyric acid. Overall, we demonstrated that LIN28B promotes CRC differentiation through the CDX2/AMACR axis.

Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy.

Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAF V600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAF V600E Lgr5 CreMin (BLM) mice, tumors have similarities to human BRAF V600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti-PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy. SIGNIFICANCE: Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene-microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAF V600E Lgr5 CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade.This article is highlighted in the In This Issue feature, p. 1601.

The number of microspheres in Y90 radioembolization directly affects normal tissue radiation exposure.

PURPOSE: In Y90 radioembolization, the number of microspheres infused varies by more than a factor of 20 over the shelf-life of the glass radioembolization device. We investigated the effect of the number of Y90 microspheres on normal liver tissue. METHOD: Healthy pigs received lobar radioembolization with glass Y90 microspheres at 4, 8, 12, and 16 days post-calibration, representing a > 20× range in the number of microspheres deposited per milliliter in tissue. Animals were survived for 1-month post-treatment and the livers were explanted and scanned on a micro CT system to fully characterize the microscopic distribution of individual microspheres. A complete 3D microdosimetric evaluation of each liver was performed with a spatially correlated analysis of histopathologic effect. RESULTS: Through whole-lobe microscopic identification of each microsphere, a consistent number of microspheres per sphere cluster was found at 4, 8, and 12 days postcalibration, despite an 8-fold increase in total microspheres infused from days 4 to 12. The additional microspheres instead resulted in more clusters formed and, therefore, a more homogeneous microscopic absorbed dose. The increased absorbed-dose homogeneity resulted in a greater volume fraction of the liver receiving a potentially toxic absorbed dose based on radiobiologic models. Histopathologic findings in the animals support a possible increase in normal liver toxicity in later treatments with more spheres (i.e., ≥ day 12) compared to early treatments with less spheres (i.e., ≤ day 8). CONCLUSION: The microdosimetric evidence presented supports a recommendation of caution when treating large volumes (e.g., right lobe) using glass 90Y microspheres at more than 8 days post-calibration, i.e., after "2nd week" Monday. The favorable normal tissue microscopic distribution and associated low toxicity of first week therapies may encourage opportunities for dose escalation with glass microspheres and could also be considered for patients with decreased hepatic reserve.

Does Etiology of Pancreatitis Matter? Differences in Outcomes Among Patients With Post-Endoscopic Retrograde Cholangiopancreatography, Acute Biliary, and Alcoholic Pancreatitis.

OBJECTIVES: We compared outcomes of acute alcoholic pancreatitis (AAP), acute biliary pancreatitis (ABP), and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS: This was a retrospective cohort study conducted at a tertiary care center between June 2007 and June 2012. RESULTS: A total of 300 (68%) patients were diagnosed with AAP, 88 (20%) with ABP, and 55 (12%) with PEP. Longer length of hospital stay (LOHS) was more common in ABP (23%) as compared with AAP (10%) and PEP (7%, P = 0.025). Pseudocyst (P = 0.048), organ failure (OF) (P = 0.01), need for interventions (P ≤ 0.001), and mortality (P = 0.002) occurred more in ABP as compared with other groups. Systemic inflammatory response syndrome was associated with LOHS of more than 10 days (P = 0.01) and multi-OF (P = 0.05). Chronic pancreatitis was associated more with pseudocyst (P < 0.001) and mortality (P = 0.03). Serum urea nitrogen of greater than 25 g/dL predicted LOHS of more than 10 days (P = 0.02), OF (P < 0.001), multi-OF (P < 0.001), and persistent OF (P < 0.001). CONCLUSIONS: Acute biliary pancreatitis is a more severe disease compared with PEP and AAP. Chronic pancreatitis, systemic inflammatory response syndrome, and high serum urea nitrogen are important predictors of morbidity.

Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic.

Mucus-invasive bacterial biofilms are identified on the colon mucosa of approximately 50% of colorectal cancer (CRC) patients and approximately 13% of healthy subjects. Here, we test the hypothesis that human colon biofilms comprise microbial communities that are carcinogenic in CRC mouse models. Homogenates of human biofilm-positive colon mucosa were prepared from tumor patients (tumor and paired normal tissues from surgical resections) or biofilm-positive biopsies from healthy individuals undergoing screening colonoscopy; homogenates of biofilm-negative colon biopsies from healthy individuals undergoing screening colonoscopy served as controls. After 12 weeks, biofilm-positive, but not biofilm-negative, human colon mucosal homogenates induced colon tumor formation in 3 mouse colon tumor models (germ-free ApcMinΔ850/+;Il10-/- or ApcMinΔ850/+ and specific pathogen-free ApcMinΔ716/+ mice). Remarkably, biofilm-positive communities from healthy colonoscopy biopsies induced colon inflammation and tumors similarly to biofilm-positive tumor tissues. By 1 week, biofilm-positive human tumor homogenates, but not healthy biopsies, displayed consistent bacterial mucus invasion and biofilm formation in mouse colons. 16S rRNA gene sequencing and RNA-Seq analyses identified compositional and functional microbiota differences between mice colonized with biofilm-positive and biofilm-negative communities. These results suggest human colon mucosal biofilms, whether from tumor hosts or healthy individuals undergoing screening colonoscopy, are carcinogenic in murine models of CRC.

Multiple Immune-Suppressive Mechanisms in Fibrolamellar Carcinoma.

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8+ cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1+ tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1+ tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8+ T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC.

Evaluation of Peritumoral Fibrosis in Metastatic Colorectal Adenocarcinoma to the Liver Using Digital Image Analysis.

Objectives: It is challenging to separate peritumoral fibrosis from fibrosis due to chronic liver disease in mass-directed liver biopsies. We evaluated the distance that peritumoral fibrosis extends from metastatic colorectal adenocarcinoma in liver. Methods: Peritumoral and distant uninvolved liver trichrome stains from 25 cases were analyzed using digital image analysis. Fibrosis was quantitated at concentric intervals from each tumor and in uninvolved liver. Results: There was a 3.9 fold (range 0.9-18.6) median increase in fibrosis in the first 0.5 mm of peritumoral liver compared to distant liver. Fibrosis levels returned to baseline at median 2.5 mm (interquartile range 1.5-5.0 mm) from tumor. Conclusions: Fibrosis is markedly increased in peritumoral liver. Fibrosis levels returned to baseline by 5 mm from tumor in approximately 75% of cases. Pathologists should be cautious of fibrosis in mass-directed liver biopsies without at least 5 mm of liver tissue distal to the mass.

Stylet slow-pull versus standard suction for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic lesions: a multicenter randomized trial.

BACKGROUND AND STUDY AIM: Standard endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) procedures involve use of no-suction or suction aspiration techniques. A new aspiration method, the stylet slow-pull technique, involves slow withdrawal of the needle stylet to create minimum negative pressure. The aim of this study was to compare the sensitivity of EUS-FNA using stylet slow-pull or suction techniques for malignant solid pancreatic lesions using a standard 22-gauge needle. PATIENTS AND METHODS: Consecutive patients presenting for EUS-FNA of pancreatic mass lesions were randomized to the stylet slow-pull or suction techniques using a 22-gauge needle. Both techniques were standardized for each pass until an adequate specimen was obtained, as determined by rapid on-site cytology examination. Patients were crossed over to the alternative technique after four nondiagnostic passes. RESULTS: Of 147 patients screened, 121 (mean age 64 ±â€Š13.8 years) met inclusion criteria and were randomized to the stylet slow-pull technique (n = 61) or the suction technique (n = 60). Technical success rates were 96.7 % and 98.3 % in the slow-pull and suction groups, respectively (P > 0.99). The sensitivity for malignancy of EUS-FNA was 82 % in the slow-pull group and 69 % in the suction group (P = 0.10). The first-pass diagnostic rate (42.6 % vs. 38.3 %; P = 0.71), acquisition of core tissue (60.6 % vs. 46.7 %; P = 0.14), and the median (range) number of passes to diagnosis (2 1 2 3 vs. 1 1 2; P = 0.71) were similar in the slow-pull and suction groups, respectively. CONCLUSIONS: The stylet slow-pull and suction techniques both offered high and comparable diagnostic sensitivity with a mean of 2 passes required for diagnosis of solid pancreatic lesions. The endosonographer may choose either technique during FNA.

MODIFIED ALVARADO SCORE IN CHILDREN WITH DIAGNOSIS OF APPENDICITIS.

Background: Appendicitis is one of the most common abdominal emergency. Some predictive scoring systems are recommended to decrease the rate of negative appendectomy. Aim: To evaluate sensitivity, specificity, positive predictive value, and negative predictive value of modified Alvarado score in children who underwent appendectomy. Methods: Four hundred children with initial diagnosis of appendicitis were randomly selected from patients who underwent appendectomy. Modified Alvarado score was used for evaluation of the appendicitis, that was confirmed using histology. Results: Of modified Alvarado score components, anorexia; nausea and vomiting and rebound tenderness were significantly more common in children with positive appendectomy in contrast to patients with negative appendectomy. Sensitivity, specificity, positive predictive value, and negative predictive value for modified Alvarado score were: 91.3%; 38.4%; 87.7%; and 51.2% respectively. Conclusion: Alvarado score has high sensitivity but low specificity for diagnosis of acute appendicitis in children.

Racional: A apendicite é uma das emergências abdominais mais comuns. Alguns sistemas de pontuação preditivos são recomendados para diminuir a taxa de apendicectomia negativa. Objetivo: Avaliar a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do escore de Alvarado modificado em crianças submetidas à apendicectomia. Métodos: Quatrocentos crianças com diagnóstico inicial de apendicite foram selecionadas aleatoriamente de pacientes submetidos à apendicectomia. A pontuação de Alvarado modificada foi utilizada para avaliação do quadro, que foi confirmado por meio de histologia. Resultados: Anorexia; náuseas, vômitos e desconforto abdominal foram significativamente mais comuns em crianças com apendicectomia positiva, em contraste com casos negativos pelo escore de Alvarado modificado. A sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para o escore de Alvarado modificado foram: 91,3%; 38,4%; 87,7%; e 51,2%, respectivamente. Conclusão: O escore de Alvarado possui alta sensibilidade, mas baixa especificidade para o diagnóstico de apendicite aguda em crianças.

Modified alvarado score in children with diagnosis of appendicitis / Escore alvarado modificado em crianças com diagnóstico de apendicite

ABSTRACT Background: Appendicitis is one of the most common abdominal emergency. Some predictive scoring systems are recommended to decrease the rate of negative appendectomy. Aim: To evaluate sensitivity, specificity, positive predictive value, and negative predictive value of modified Alvarado score in children who underwent appendectomy. Methods: Four hundred children with initial diagnosis of appendicitis were randomly selected from patients who underwent appendectomy. Modified Alvarado score was used for evaluation of the appendicitis, that was confirmed using histology. Results: Of modified Alvarado score components, anorexia; nausea and vomiting and rebound tenderness were significantly more common in children with positive appendectomy in contrast to patients with negative appendectomy. Sensitivity, specificity, positive predictive value, and negative predictive value for modified Alvarado score were: 91.3%; 38.4%; 87.7%; and 51.2% respectively. Conclusion: Alvarado score has high sensitivity but low specificity for diagnosis of acute appendicitis in children.

RESUMO Racional: A apendicite é uma das emergências abdominais mais comuns. Alguns sistemas de pontuação preditivos são recomendados para diminuir a taxa de apendicectomia negativa. Objetivo: Avaliar a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do escore de Alvarado modificado em crianças submetidas à apendicectomia. Métodos: Quatrocentos crianças com diagnóstico inicial de apendicite foram selecionadas aleatoriamente de pacientes submetidos à apendicectomia. A pontuação de Alvarado modificada foi utilizada para avaliação do quadro, que foi confirmado por meio de histologia. Resultados: Anorexia; náuseas, vômitos e desconforto abdominal foram significativamente mais comuns em crianças com apendicectomia positiva, em contraste com casos negativos pelo escore de Alvarado modificado. A sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para o escore de Alvarado modificado foram: 91,3%; 38,4%; 87,7%; e 51,2%, respectivamente. Conclusão: O escore de Alvarado possui alta sensibilidade, mas baixa especificidade para o diagnóstico de apendicite aguda em crianças.

Endoscopic suturing for the prevention of stent migration in benign upper gastrointestinal conditions: a comparative multicenter study.

BACKGROUND AND STUDY AIMS: Fully covered self-expandable metal stents (FCSEMSs) have increasingly been used in benign upper gastrointestinal (UGI) conditions; however, stent migration remains a major limitation. Endoscopic suture fixation (ESF) may prevent stent migration. The aims of this study were to compare the frequency of stent migration in patients who received endoscopic suturing for stent fixation (ESF group) compared with those who did not (NSF group) and to assess the impact of ESF on clinical outcome. PATIENTS AND METHODS: This was a retrospective study of patients who underwent FCSEMS placement for benign UGI diseases. Patients were divided into either the NSF or ESF group. Outcome variables, including stent migration, clinical success (resolution of underlying pathology), and adverse events, were compared. RESULTS: A total of 125 patients (44 in ESF group, 81 in NSF group; 56 benign strictures, 69 leaks/fistulas/perforations) underwent 224 stenting procedures. Stent migration was significantly more common in the NSF group (33 % vs. 16 %; P = 0.03). Time to stent migration was longer in the ESF group (P = 0.02). ESF appeared to protect against stent migration in patients with a history of stent migration (adjusted odds ratio [OR] 0.09; P = 0.002). ESF was also significantly associated with a higher rate of clinical success (60 % vs. 38 %; P = 0.03). Rates of adverse events were similar between the two groups. CONCLUSIONS: Endoscopic suturing for stent fixation is safe and associated with a decreased migration rate, particularly in patients with a prior history of stent migration. It may also improve clinical response, likely because of the reduction in stent migration.

Liver regeneration after major liver hepatectomy: Impact of body mass index.

BACKGROUND: Obese patients may present with metabolic abnormalities that impact liver regeneration. We sought to assess the impact of body mass index (BMI) on liver volume regeneration index (RI) and kinetic growth rate (KGR) among patients undergoing liver resection. METHODS: The study included 102 patients undergoing major hepatectomy (≥3 segments) between July 2004 and April 2015 and stratified the patients by preoperative BMI, number of segments resected, and postoperative remnant liver volume (RLVp) to total liver volume ratio. Resected volume at operation was subtracted from total liver volume to calculate postoperative RLVp. RI was defined as the relative increase in RLV within 2 months [(RLV2m-RLVp)/RLVp] and 7 months [(RLV7m-RLVp)/RLVp] postoperatively; KGR was calculated as RI divided by time postoperatively (weeks). RESULTS: Median patient age was 59.6 years (interquartile range 48.1-68.7 years), and most patients were men (52.0%). Liver failure was associated with the KGR at 2 months (KGR2m) and was greater among patients with KGR2m <2.5% per week (KGR <2.5%, 18.5% vs KGR ≥ 2.5%, 4.6%; P = .04). Although RI and KGR within 2 and 7 months postoperatively were similar among all patients, after excluding patients with fibrosis, obese (0.42% per week) and overweight patients (0.29% per week) had lesser KGR2-7m compared with patients of normal BMI (0.82% per week; P < .05). Additionally, risk of a major complication was greatest among obese patients (normal weight, 8.1% vs overweight, 12.9% vs obese, 29.4%; P = .04). CONCLUSION: BMI did not impact liver regeneration during the first 2 months. In contrast, KGR per week between 2 and 7 months postoperatively was less among overweight and obese patients.