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Improved post-operative outcomes have been demonstrated in gastrointestinal procedures where a narcotic sparing strategy has been utilized. Data for pancreaticoduodenectomy (PD) patients is limited. This study reviews an institutional database for outcomes based on initial analgesic strategy.1004 consecutive patients who underwent PD at Emory University between 2010 and 2017, were included in the analysis. Patients were divided into groups based on primary analgesic strategy employed: epidural alone (EPI), patient controlled opiate analgesia (PCA), dual (dual-PCA/EPI) and other (non-PCA/EPI). Postoperative outcomes for each group were analyzed utilizing univariate and multivariate linear regression.448 (44.6%) patients were treated with EPI, 300 (29.9%) were given a PCA, 78 (7.8%) had dual-PCA/EPI and 178 (17.7%) had non-PCA/EPI analgesia. On univariate analysis, increased BMI (p = 0.030), PCA use (p 0.001), venous thromboembolism (VTE) (p 0.001), post-operative pancreatic fistula (POPF) (p 0.001) and Ileus/delayed gastric emptying (DGE) (p 0.001) were all correlated with increased LOS. On multivariate linear regression, VTE (b-coefficient 9.07, p = 0.004) POPF (8.846, p = 0.001), Ileus/DGE (4.464, p = 0.004) and PCA use (1.75, p = 0.003) were associated with significantly increased LOS.A primary narcotic sparing strategy is associated with a significantly reduced LOS and lower rates of Ileus/DGE. Mean opiate usage was significantly lower in the EPI and non-EPI/PCA groups.

Retrospective review of prospectively collected data.To analyze the postoperative factors that led delayed discharge in patients who would have been eligible for ambulatory lumbar fusion (ALF).Assessing postoperative inefficiencies is vital to increase the feasibility of ALF.Patients who underwent single-level minimally invasive transforaminal lumbar interbody fusion and would have met the eligibility criteria for ALF were included. Length of stay (LOS); time in postanesthesia recovery unit (PACU); alertness and neurological examination, and pain scores at three and six hours; type of analgesia; time to physical therapy (PT) visit; reasons for PT nonclearance; time to per-oral (PO) intake; time to voiding; time to readiness for discharge were assessed. Time taken to meet each discharge criterion was calculated. Multiple regression analyses were performed to study the effect of variables on postoperative parameters influencing discharge.Of 71 patients, 4% were discharged on the same day and 69% on postoperative day 1. PT clearance was the last-met discharge criterion in 93%. Sixty-six percent did not get PT evaluation on the day of surgery. Seventy-six percent required intravenous opioids and60% had adequate pain control. Twenty-six percent had orthostatic intolerance. The median postoperative LOS was 26.9 hours, time in PACU was 4.2 hours, time to PO intake was 6.5 hours, time to first void was 6.3 hours, time to first PT visit was 17.7 hours, time to PT clearance was 21.8 hours, and time to discharge readiness was 21.9 hours. Regression analysis showed that time to PT clearance, time to PO intake, time to voiding, time in PACU, and pain score at three hours had a significant effect on LOS.Unavailability of PT, surgery after 1 pm , orthostatic intolerance, inadequate pain control, prolonged PACU stay, and long feeding and voiding times were identified as modifiable factors preventing same-day discharge.4.

Meningiomas are the most common type of primary brain tumor; they have a low risk for extracranial metastases, which are primarily associated with increased tumor grade. Hepatic metastases from cranial meningiomas are extremely rare, with only a paucity of cases reported in the literature and no standardized approach to management. Herein, we report a case of an incidentally discovered giant (>20 cm) metastatic meningioma to the liver treated with surgical resection 10 years following resection of a low-grade cranial meningioma. This report also highlights the use of (68Ga) DOTATATE PET/CT as the diagnostic imaging modality of choice when evaluating for meningioma metastases. To our knowledge, this report describes the largest hepatic metastasis from a cranial meningioma to undergo surgical resection in the literature.

Supplemental Figures S1-S7

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer. Hsp90 regulates a diverse array of cellular processes of relevance to both the tumor and the immune system. However, to date the role of Hsp90 in PSC/CAF has not been explored in detail. We hypothesized that Hsp90 inhibition would limit inflammatory signals, thereby reprogramming the PDAC tumor microenvironment to enhance sensitivity to PD-1 blockade. Treatment of immortalized and primary patient PSC/CAF with the Hsp90 inhibitor XL888 decreased IL6, a key cytokine that orchestrates immune changes in PDAC at the transcript and protein level in vitro. XL888 directly limited PSC/CAF growth and reduced Jak/STAT and MAPK signaling intermediates and alpha-SMA expression as determined via immunoblot. Combined therapy with XL888 and anti–PD-1 was efficacious in C57BL/6 mice bearing syngeneic subcutaneous (Panc02) or orthotopic (KPC-Luc) tumors. Tumors from mice treated with both XL888 and anti–PD-1 had a significantly increased CD8+ and CD4+ T-cell infiltrate and a unique transcriptional profile characterized by upregulation of genes associated with immune response and chemotaxis. These data demonstrate that Hsp90 inhibition directly affects PSC/CAF in vitro and enhances the efficacy of anti–PD-1 blockade in vivo.

The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts >= 1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts >= 1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.

Resection of the primary (RP) in metastatic neuroendocrine tumor (NET) is controversial. The aim was to evaluate survival outcomes for RP in metastatic NET patients.Data were obtained from US hospitals at the National Cancer Database between 2004 and 2014. χ2, analysis of variance tests, univariate, and multivariate cox proportional hazards models were evaluated. Kaplan-Meier curves and log-rank tests conducted to compare the survival difference of patient characteristics.A total of 2361 patients were identified. The mean age was 62.1 years (standard deviation, 13 years), male-to-female ratio 1:1; 33% were small intestine, 26.3% pancreas, and 24.4% lung; 69.6% were well-differentiated; and 42.5% underwent RP. The 5-year overall survival (OS) was significantly improved for patients who underwent RP in small intestine (5-year OS, 63.9% vs 44.2%), lung (5-year OS, 65.4% vs 20.2%), and pancreas tumors (5-year OS, 75.6% vs 30.6%). On multivariate analysis, RP (hazard ratio, 0.46; 95% confidence interval, 0.29-0.73; P0.001), female, year of diagnosis 2010-2014, margin, Charlson-Deyo score less than 2, and age less than 51 years, were associated with better OS.Resection of the primary in metastatic well-differentiated NET is associated with improved OS compared with no RP.

Minimally invasive approaches to major liver resection have been limited by presumed difficulty of the operation. While some concerns arise from mastering the techniques, factors such as tumor size and liver parenchymal features have anecdotally been described as surrogates for operative difficulty. These factors have not been systematically studied for minimally invasive right hepatectomy (MIRH). Seventy-five patients who underwent MIRH during 2007–2016 by the senior author were evaluated; these were compared to control group of open right hepatectomy. Demographics, operative, and post-operative variables were collected. Operative times and estimated blood loss, two objective parameters of operative difficulty were correlated to volume of hepatic resection, parenchymal transection diameter and liver parenchymal features using regression analysis. Thirty-eight (50.6%) resections were performed for malignant indications. Average tumor size was 5.7 cm (±3.6), mean operative time was 196 min (±74), and mean EBL was 220 mL (±170). Average transection diameter was 10.1 cm (±1.7). There was no correlation between operative difficulty with parenchymal transection diameter or presence of steatosis. Blood loss was higher with increased right hepatic lobe volume and body mass index. This analysis of a very defined anatomical resection suggests that the often quoted radiographic and pathologic features indicative of a challenging procedure were not significant in determining operative difficulty.

Understanding students' development academic language skills within informational writing is only beginning to emerge. We evaluate Grade 5 and Grade 8 students' writing (in the genre of descriptive informational writing in response to a single text) to determine which metrics may be the most indicative of academic language and what role they play. The roles include contributions to writing quantity, quality, and level of narrativity. An individual differences design was used to compare several word and sentence-level features to determine the degree to which the features signal academic language at the beginning and end of middle school. Results suggest that frequency of longer words may be the most useful measure of academic language in informational writing and that several sentence-level measures may challenge our current conceptualization of quality writing. Results provide promising avenues for the measurement and assessment of academic language in writing that detects development as well as important finer grained malleable aspects of written composition.

Ion channels are potentially exploitable as pharmacological targets to treat asthma. This study evaluated the role of KCa3.1 channels, encoded by Kcnn4, in regulating the gene expression of mouse airway epithelium and the development of asthma traits. We used the ovalbumin (OVA) challenge as an asthma model in wild-type and Kcnn4−/− mice, performed histological analysis, and measured serum IgE to evaluate asthma traits. We analyzed gene expression of isolated epithelial cells of trachea or bronchi using mRNA sequencing and gene ontology and performed Ussing chamber experiments in mouse trachea to evaluate anion secretion. Gene expression of epithelial cells from mouse airways differed between trachea and bronchi, indicating regional differences in the inflammatory and transepithelial transport properties of proximal and distal airways. We found that Kcnn4 silencing reduced mast cell numbers, mucus, and collagen in the airways, and reduced the amount of epithelial anion secretion in the OVA-challenged animals. In addition, gene expression was differentially modified in the trachea and bronchi, with Kcnn4 genetic silencing significantly altering the expression of genes involved in the TNF pathway, supporting the potential of KCa3.1 as a therapeutic target for asthma.

Aortic aneurysms occur concomitantly with malignancy in approximately 1.0-17.0% of patients. There is little published information regarding the effects of subsequent oncological therapies on aortic aneurysm growth. The aim of this study was to determine the effects of chemoradiation therapies on the natural progression of small abdominal aortic aneurysm (AAA), thoracic aortic aneurysm, and thoracoabdominal aortic aneurysm.Patients with aortic aneurysms with and without malignancy between 2005 and 2017 were identified within institutional databases using Current Procedural Terminology and International Classification of Disease codes. Inclusion criteria included complete chemotherapy documentation, a minimum of 3 multiplanar axial/coronal imaging or ultrasonography before, during, and after receiving therapy or 2 studies for patients without malignancy. Propensity matching, Cox and linear regression, and Kaplan-Meier survival analyses were performed.A total of 159 (172 aneurysms) patients with malignancy and 127 (149 aneurysms) patients without malignancy were included. Average patient demographics were 74.4 ± 9.8-years-old, Caucasian (66.8%), male (70.3%), with hypertension (71.1%), current smoking (24.5%), coronary atherosclerotic disease (26.2%), and AAA (71.0%). The most common malignancy was lung cancer (48.4%) with most chemotherapy regimens including a platinum-based alkylating agent and concurrent antimetabolite (56.0%). The overall median follow-up time was 28.2 (range 3.1-174.4) months. Aortic aneurysms in patients without malignancy grew to larger sizes (4.43 ± 0.96 vs. 4.14 ± 1.00, P = 0.008) with similar median growth rates (0.12 vs. 0.12 cm/year, P = 0.090), had more atypical morphologic features (14.1% vs. 0.6%, P 0.001), more frequently underwent repair (22.1% vs. 8.7%, P = 0.001), and more frequently required emergency repair for rupture (5.4% vs. 0.0%, P = 0.087). Cox regression identified initial aortic size ≥4.0 cm (hazard ratio [HR] 3.028), AAA (HR 2.146), chronic aortic findings (3.589), and the use of topoisomerase inhibitors (HR 2.694). Linear regression demonstrated increased growth rates predicted by antimetabolite chemotherapy (β 0.170), initial aortic size (β 0.086), and abdominal aortic location (β 0.139, all P 0.002).Small aortic aneurysms with concomitant malignancies are discovered at smaller initial sizes, grow at similar rates, require fewer interventions, and have fewer ruptures and acute dissections than patients without malignancy. Antimetabolite therapies modestly accelerate aneurysmal growth, and patients receiving topoisomerase inhibitors may require earlier repair. Patients with concomitant disease can be confidently treated according to standard institutional aneurysm surveillance protocols. Overall, we recommend treatment of the malignancy before small aortic aneurysm repair as these aneurysms behave similarly to those in patients without malignancy.

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer. Hsp90 regulates a diverse array of cellular processes of relevance to both the tumor and the immune system. However, to date the role of Hsp90 in PSC/CAF has not been explored in detail. We hypothesized that Hsp90 inhibition would limit inflammatory signals, thereby reprogramming the PDAC tumor microenvironment to enhance sensitivity to PD-1 blockade. Treatment of immortalized and primary patient PSC/CAF with the Hsp90 inhibitor XL888 decreased IL6, a key cytokine that orchestrates immune changes in PDAC at the transcript and protein level in vitro. XL888 directly limited PSC/CAF growth and reduced Jak/STAT and MAPK signaling intermediates and alpha-SMA expression as determined via immunoblot. Combined therapy with XL888 and anti–PD-1 was efficacious in C57BL/6 mice bearing syngeneic subcutaneous (Panc02) or orthotopic (KPC-Luc) tumors. Tumors from mice treated with both XL888 and anti–PD-1 had a significantly increased CD8+ and CD4+ T-cell infiltrate and a unique transcriptional profile characterized by upregulation of genes associated with immune response and chemotaxis. These data demonstrate that Hsp90 inhibition directly affects PSC/CAF in vitro and enhances the efficacy of anti–PD-1 blockade in vivo.

The cause of most pancreatic and periampullary cancers (PAC) is unknown. Recently, anatomic variations such as pancreatobiliary maljunction have been recognized as risk factors, similar to Barrett-related gastro-esophageal cancers.Pre-operative MRI from 860 pancreatic/biliary resections, including 322 PACs, were evaluated for low-union (cystic duct joining the common hepatic duct inside of the pancreas or within 5 mm of the pancreatic border) RESULTS: Low-union, seen10% of the population, was present in 44% of PACs (73% distal bile duct/cholangiocarcinoma, 42% pancreatic head, and 34% ampullary). It was significantly lower(11%) in conditions without connection to the ductal system (thus not exposed to the ductal/biliary tract contents), namely mucinous cystic neoplasms and intrahepatic cholangiocarcinomas(p0.0001). Intra-pancreatic type low-union was seen in 16% of PACs versus 2% of controls(p0.0001).This study establishes an association between low-union and PACs, and points to an anatomy-induced chemical/bilious carcinogenesis. This may explain why most pancreas cancers are in the head. It is possible that the same chemical milieu, caused by conditions other than low-union/insertion, may also play a role in the remaining half of PACs. This opens various treatment opportunities including milieu modifications (chemoprevention), focused screening of at-risk patients, and early detection with possible corrective actions.

Existing research suggests patients with blood group O are less likely to develop pancreatic ductal adenocarcinoma (PDAC) compared to those with non-O blood groups, and that survival from PDAC may be affected by ABO blood type. This study assessed survival outcomes in PDAC patients who underwent pancreatoduodenectomy (PD) in one health system.From 2010 to 2017, demographic, operative, chemotherapy and survival data for patients undergoing PD at Emory Healthcare were reviewed. Patients with blood type AB were excluded due to small sample size. The relationship between ABO blood group and survival was analyzed using Kaplan-Meier survival curves and multivariate cox proportional regression analysis.Of 449 PDAC patients assessed, 204 (45.4%), 60 (13.4%) and 185 (41.2%) were blood groups A, B and O, respectively. Patients were well matched in clinicopathologic characteristics. Median survival did not differ by blood group (p = 0.82), and this relationship remained insignificant on cox regression analysis (p = 0.15). On multivariate analysis, lymph node positivity (p 0.001) and increasing age (p = 0.001) were associated with reduced survival.In contrast to recent reports, this larger study found that blood group did not impact overall survival among patients undergoing PD for PDAC.

Background The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established. Methods In total, 127 ACs with invasive carcinomas measuring ≥3 mmthat had adequate tissue were analyzed immunohistochemically. Results MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1-PMS2 loss were negative for BRAF V600E mutation, suggesting a Lynch syndrome association. MMR-deficient tumors (n = 23), comparedwith MMR-intact tumors (n = 104), showed a striking male predominance (male:female ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; P = .04). More important, patients who had MMR-deficient tumors had better clinical outcomes, with a 5-year overall survival rate of 68% versus 45% (P = .03), which was even more pronounced in those who had higher Tclassification (5-year overall survival, 69% vs 34%; P = .04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing-border invasion, and tumor-infiltrating immune cells, and it occurred more frequently in ampullary-duodenal type tumors. Programed cell death-ligand 1 (PD-L1) levels analyzed in the 22 MMR-deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR-deficient carcinomas expressed PD-L1 in 33% of tumors cells according to the criteria for a combined positive score ≥1, but all were negative according to the tumor proportion score≥1 method. Conclusions In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch-suggestive profile, thus routine testing is warranted. Male gender, pushing-border infiltration, ampullary-duodenal origin, medullary histology, and tumor-related inflammation have a significantly higher association with MMR deficiency. MMR-deficient tumors have less aggressive behavior. PD-L1 expression is common in medullary-phenotype ACs, thus immunotherapy should be considered at least for this group.

Background Postoperative returns to acute care represent fragmented care, are costly, and often evolve into readmission. Reduction of postoperative readmissions and emergency department visits represents an opportunity to improve quality of care and decrease resource use. The aim of this study was to assess the impact of 2 failure modes and effects analysis-guided quality improvement interventions on return to acute care within 30 days postoperatively. Methods An American College of Surgeons NSQIP database analysis of adult patients treated by a single hepatopancreatobiliary surgeon at a quaternary academic center was performed. Two failure modes and effects analysis-guided quality improvement interventions were assessed in a staged fashion, including a post-discharge phone call follow-up, and a preoperative clinic visit to discuss plans of care. The primary end point of interest was return to acute care (readmission or emergency department use) within 30 days from postoperative discharge. Results During the 4-year study period, 684 patients underwent a hepatopancreatobiliary operation. After the implementation of the failure modes and effects analysis interventions, the baseline 30-day readmission rate was reduced by 48% post intervention (13.5% vs 6.9%; p = 0.011). This impact was sustained, with a readmission rate below the lowest baseline in 5 of 6 postintervention quarters. Short-stay readmissions were reduced by > 76% after the interventions (28.5% vs 6.6%). Post-discharge emergency department visits were also reduced by nearly 40% after initiation of both failure modes and effects analysis-guided quality improvement interventions (11.3% vs 6.9%; p = 0.125), which showed similar sustained response. Conclusions The results from this study can be used to help identify, develop, and test interventions to optimize emergency department use and readmission to reduce healthcare costs and improve patient quality of life.

Background The amount of IV fluids sufficient to prevent post-operative acute kidney injury (AKI) during pancreaticoduodenectomy (PD) is unknown. We assessed the restrictive IOIVF use in PD on the rate of post-operative AKI, delayed gastric emptying and ileus, and pancreatic fistulas (POPF). Methods Patients who underwent PD between 2012 and 2017 were reviewed. Univariate and multivariate analyses looked for association between pre- and intra-operative factors on AKI, ileus and POPF. Results Of 395 included patients, 97, 172, and 126 patients received less than 1000 mL (ultra-restrictive), 1000 mL to less than 2000 mL (restrictive), and 2000 mL and greater (nonrestrictive) normalized total IOIVF respectively. Of these 23 (24.2%), 34(20.4%), and 21(17.4%) developed AKI respectively, most of them mild. There was no difference in odds of developing AKI, ileus, or pancreatic fistula among fluid groups. While there was no difference in Clavien-Dindo III-IV complications, the incidence of Clavien-Dindo type I-II complications was lower in the restricted fluid groups. Discussion Restricted fluids did not lead to higher AKI rates but were associated with fewer low-grade complications.

BACKGROUND. Pancreatoduodenectomy (PD) for duodenal adenoma (DA) resection may be associated with excessive surgical risk for patients with potentially benign lesions, given the absence of pancreatic duct obstruction. We examined factors associated with final malignant pathology and evaluated the postoperative course of patients with DA versus pancreatic ductal adenocarcinoma (PDAC). METHODS. We retrospectively analyzed patients with DA who underwent PD from 2008 to 2018 and assessed the accuracy rate of preoperative biopsy and factors associated with final malignant pathology. Complications for DA patients were compared with those of matched PDAC patients. RESULTS. Forty-five consecutive patients who underwent PD for DA were identified, and the preoperative biopsy false negative rate was 29. Factors associated with final malignant pathology included age over 70 years, preoperative biliary obstruction, and common bile duct diameter > 8 mm (p < 0.05). Compared with patients with PDAC (n = 302), DA patients experienced more major complications (31% vs. 15%, p < 0.01), more grade C postoperative pancreatic fistulas (9% vs. 1%, p < 0.01), and greater mortality (7% vs. 2%, p < 0.05). Propensity score matched patients with DA had more major complications following PD (32% vs. 12%, p < 0.05). CONCLUSIONS. Preoperative biopsy of duodenal adenomas is associated with a high false-negative rate for malignancy, and PD for DA is associated with higher complication rates than PD for PDAC. These results aid discussion among patients and surgeons who are considering observation versus PD for DA, especially in younger patients without biliary obstruction, who are less likely to harbor malignancy.

Preinvasive tumor-forming gallbladder neoplasms that are composed of small, non-mucinous tubules with complex architecture remain a poorly characterized group. Here, we evaluated the clinicopathological characteristics of this entity. Twenty-eight examples were analyzed. Tumors were invariably pedunculated polyps with thin stalks, often presented as loosely attached intraluminal nodules, with cauliflower architecture (akin to cholesterol polyps) comprised of compact, back-to-back acinar-like, small tubular units with minimal/no cytoplasm showing variable complexity, creating a picture distinct from the other tubular type dysplasia in the gallbladder. Their limited stroma showed distinctive amorphous amyloid-like hyalinization (39%). While some had round nuclei with single prominent nucleoli, others exhibited slightly more elongated nuclei with washed out chromatin reminiscent of papillary thyroid carcinoma. Squamoid/meningothelial-like morules (71%) and subtle neuroendocrine cell clusters (39%) were frequent. The level of cytoarchitectural atypia qualified as high-grade dysplasia (HGD) in all cases, but none were invasive. The background mucosa showed no dysplasia, but cholesterolosis. The majority (n = 8/12) showed diffuse MUC6 expression and lacked MUC5AC expression. Based on these observations, 635 gallbladder carcinomas were re-analyzed for residual/adjacent lesions with entity-defining characteristics disclosed here, and none could be identified. Preinvasive tubular non-mucinous neoplasm of the gallbladder, which we propose to classify as intracholecystic tubular non-mucinous neoplasm, is a clinicopathologically discrete entity, which tends to occur in uninjured gallbladders and in association with cholesterol polyps. By being tubular, non-mucinous and MUC6-positive, it is akin to intraductal tubulopapillary neoplasms of pancreatobiliary tract, but it is also different in many other aspects. Although their cytoarchitectural complexity warrants an HGD/carcinoma classification, they do not show invasion and their distinct characteristics warrant their separate classification.

Resumen: Objetivo: establecer la prevalencia y la gravedad de la enfermedad periodontal en pacientes con síndrome coronario agudo sin comorbilidades, que ingresan al programa de rehabilitación cardíaca en la Fundación Clínica Shaio. Métodos: se examinaron 83 pacientes con diagnóstico de síndrome coronario agudo sin comorbilidades y los siguientes diagnósticos: angina inestable (n = 27), infarto de miocardio con elevación del segmento ST (STEMI) (n = 34) e infarto de miocardio sin elevación del segmento ST (NSTEMI) (n = 22). La prevalencia y la gravedad de la enfermedad periodontal fueron evaluadas con el índice periodontal de los Centros para el Control y la Prevención de Enfermedades (CDC). Se compararon entre los grupos índice clínico, placa, cálculo, hemorragia gingival, profundidad de sondaje y nivel de inserción clínica. Resultados: la prevalencia de enfermedad periodontal fue del 97,6% y se observó periodontitis avanzada en el 38,3%. Los pacientes con STEMI mostraron la mayor gravedad de la periodontitis. Los índices clínicos inflamatorios de la enfermedad periodontal se elevaron en todos los grupos sin diferencias significativas. El nivel de inserción clínica no mostró diferencias significativas entre las condiciones cardíacas. Sin embargo, se observó mayor porcentaje de sitios con pérdida de inserción clínica (PIC) ≥ 6 mm, y sitios con una profundidad de bolsas > 6 mm, en pacientes con STEMI. Conclusión: los pacientes con síndrome coronario agudo sin comorbilidades, que ingresaron al programa de rehabilitación cardíaca para completar su tratamiento, tuvieron alta prevalencia y gravedad de la enfermedad periodontal. Es necesario hacer énfasis en el control de la enfermedad periodontal en pacientes con enfermedad coronaria. Abstract: Objective: To determine the prevalence and severity of periodontal disease in patients with acute coronary syndrome with no comorbidities admitted to a cardiac rehabilitation programme in the Clínica Shaio Foundation, Colombia. Methods: The study included a total of 83 patients diagnosed with acute coronary syndrome with no comorbidities and the following diagnoses: unstable angina (n = 27), ST-segment elevation myocardial infarction (STEMI) (n = 34), and non-ST-elevation myocardial infarction (NSTEMI) (n = 22). The prevalence and severity of periodontal disease were evaluated using the Periodontal Index of the Centres for the Control and Prevention of Diseases. A between-group comparison was made of the clinical index, plaque, calculi, gingival bleeding, probing depth, and level of clinical attachment. Results: The prevalence of periodontal disease was 97.6%, and advance periodontitis was observed in 38.3% of subjects. The patients with a STEMI showed more severe periodontitis. The inflammatory clinical indices of periodontal disease were increased in all groups, with no significant differences being observed. There were no significant differences between clinical attachment and heart conditions. However, it was observed that there was a higher percentage of locations with a loss of clinical attachment ≥ 6 mm, and locations with bag depths > 6 mm in patients with a STEMI. Conclusion: The patients with acute coronary syndrome with no comorbidities, and who entered the cardiac rehabilitation programme to complete their treatment, had a high prevalence and severity of periodontal disease. The control of periodontal disease should be emphasised in patients with coronary disease..

Background Limited literature is available on the postoperative development of impaired glucose tolerance (IGT) and new-onset diabetes mellitus (NODM) following Distal Pancreatectomy (DP). We aimed to study the post-surgical clinical evolution of IGT/DM and its association with preoperative glycemic profiles of patients undergoing DP. Methods Pre- and postoperative glycemic laboratories were measured in patients undergoing DP by the senior author from 2007–2017. Multivariate risk factor analysis was performed to determine risk factors for new-onset IGT/DM after DP. Kaplan–Meier curves were constructed for development of NODM postoperatively. Results Of 216 included patients, n = 63, n = 68 and n = 85 were preoperatively diagnosed with no-diabetes (No-DM), pre-diabetes (Pre-DM), and diabetes (DM), respectively. At 2-year follow-up, n = 37, n = 80 and n = 99 were classified as No-DM, Pre-DM or DM, respectively. Pre-diabetics had a higher risk of developing postoperative dysglycemia (RR 2.230, 95% CI 1.732–2.870, p = 0.001). Preoperative OGTT>130, HbA1c >6.0, and chronic pancreatitis were risk factors for postoperative DM. Conclusion 40% of patients undergoing DP were unaware of their dysglycemic status (pre-DM or DM) pre-operatively. At 2-year follow-up, 36% non-diabetic and 57% pre-diabetic patients had developed NODM. Appropriate pre-operative diabetic assessment is warranted for all patients undergoing pancreatic resections.

Bile cultures (BC) have routinely been used to guide empiric antibiotic therapy for developing postoperative infections. The ability of BCs to predict sensitivity and resistance patterns (SRP) of site of infection cultures (SOIC) remains controversial. The aim was to assess the concordance of pathogens and SRPs between paired BC/SOICs.Medical records of consecutive patients undergoing pancreaticoduodenectomy were reviewed between 2014 and 2018. BC/SOIC pathogens and SRPs were compared on a patient-by-patient basis and concordance (K) was assessed.Common patient characteristics of 522 included patients were 65-years-old, Caucasian (75.5%), male (54.2%), malignant indication (79.3%), and preoperative biliary stent (59.0%). Overall, 275 (89.6%) BCs matured identifiable isolates with 152 (55.2%) demonstrating polymicrobial growth. Ninety-two (17.6%) SOICs were obtained: 48 and 44 occurred in patients with and without intraoperative BCs. Stents were associated with bacteriobilia (85.7%, K = 0.947, p 0.001; OR 22.727, p 0.001), but not postoperative infections (15.2%; K = 0.302, p 0.001; OR 1.428, p = 0.122). Forty-eight patients demonstrated paired BC/SOICs to evaluate. Pathogenic concordance of this group was 31.1% (K = 0.605, p 0.001) while SRP concordance of matched pathogens was 46.7% (K = 0.167, p = 0.008).Bile cultures demonstrate poor concordance with the susceptibility/resistance patterns of postoperative infections following pancreaticoduodenectomy and may lead to inappropriate antibiotic therapies.

Better prognostication/stratification of pancreatic neuroendocrine tumors (PanNETs) is needed. In this detailed morpheomic study of 163 resected PanNETs, 11 unusual variants, some of which were not previously recognized, and others scarcely documented in the literature, were identified, and their pathologic characteristics were further analyzed. By behavior and clinicopathologic associations, these variants could be grouped into three prognostically different categories. I. More aggressive (20%). Included in this group were the variants that in average showed higher grade and stage and adverse outcome including oncocytic, plasmacytoid, lipid-rich and previously unrecognized hepatoid variants, which often had a more diffuse/broad-band growth pattern, with some also displaying discohesiveness. They were characterized by abundant cytoplasm and often had prominent nucleoli (as seen in metabolically active cells), thus the provisional name "metabolic cell phenotype." Because of their diversion from classical neuroendocrine cytomorphology, these variants created challenges on original diagnostic workup, particularly hepatoid examples, which revealed Arginase 1/Hep Par-1 expression in 50%. II. Less aggressive (10%). These cases either showed signs of maturation, including nested growth, paraganglioid pattern (which was previously unrecognized), and organoid PanNETs such as "ductulo-insular" growth, or showed symplastic/degenerative changes, and despite their paradoxically disconcerting histology, were more benevolent in behavior. III. Undetermined. There were other variants including mammary tubulolobular-like, pseudoglandular, peliotic, and sclerotic PanNETs, which although diagnostically challenging, their biologic significance could not be determined because of rarity or heterogeneous characteristics. Prognostic associations: Features that were significantly different in the more aggressive group than the less aggressive group were median size (5.0 vs 1.6 cm, p < 0.001), percentage of pT3+T4 cases (72% vs 12%, p < 0.001), Ki67 index (5.3% vs 2.3%, p = 0.001), % G2 and G3 cases (77% vs 27%, p < 0.001), and rate of lymph node and distant metastasis (96% vs 27%, p < 0.001). In stepwise logistic regression model using the 3 established prognosticators of T stage, size, and grade along with morphology, only aggressive-morphology (metabolic cell phenotype) was found to be associated with metastatic behavior with an odds ratio of 5.9 with 95% confidence interval (C.I.) 1.688 to 22.945 and p value 0.007. In conclusion, PanNETs display various morphologic patterns that are not only challenging and important diagnostically but appear to have biologic significance. Tumors with more diffuse growth of cells with nucleoli and abundant cytoplasm and/or discohesion (oncocytic, hepatoid, lipid-rich, plasmacytoid PanNETs), provisionally termed "metabolic cell phenotype," show aggressive characteristics and are an independent determinant of adverse outcome and thus may require closer post-surgical follow-up, whereas variants with more degenerative or mature features (ductuloinsular, pleomorphic, paraganglioma-like) appear to be more benevolent despite their more atypical and worrisome morphology.

Surgical resection remains the only potentially curative therapy for pancreatic ductal adenocarcinoma (PDAC). There is paucity of literature about morbidity and mortality in older patients with PDAC undergoing pancreaticoduodenectomy. This retrospective analysis evaluates the in-hospital 30-day mortality of this population utilizing the Nationwide Inpatient Sample (NIS) database.All US patients hospitalized for pancreaticoduodenectomy (Whipple procedure) were included. Data was obtained from the NIS provided by the Agency for Healthcare Research and Quality. Pancreaticoduodenectomy diagnoses were identified using Clinical Classifications Software codes based on ICD-9 between 2007 and 2010. Univariable and multivariable analyses were performed using the logistic model, weighted chi-square test, and generalized linear model.A total of 6149 patient discharges for pancreaticoduodenectomy were identified. Mean age was 64.9 years (SD ± 12.3); 21% of patients were ≥ 76 years of age. Majority were White (N = 5257, 77.9%) with a male:female ratio of 1. Patients aged 76 and older (OR: 1.76; 1.36-2.28; p .001), Hispanics (OR: 1.40; 0.92-2.13; p = .12), and high comorbidity score (OR: 5.70; 3.44-9.46; p .001) were found to be associated with a higher risk of 30-day in-hospital mortality. In the multivariable analysis, advanced age (76) remained a significant predictor of longer in-hospital length of stay (OR: 1.09; 1.04-1.14; p .001) and 30-day in-hospital mortality (OR 1.46; 1.07-2.00; p = .016). The 30-day in-hospital mortality rate for all patients across all years was 3.24%, for patients76 years 4.11% and for patients76 years 2.77%. Patients who underwent surgery at teaching hospitals (OR: 0.61; 0.42-0.88; p = .008) had a lower risk of 30-day in-hospital mortality compared to non-teaching hospitals.In-hospital 30 day mortality was higher in selected older patients with PDAC undergoing pancreaticoduodenectomy. Mortality was lower at high volume and teaching centers. Further stringent selection criteria are needed to decrease mortality in the older population.

Army family member health and resilience directly impact soldier readiness and are critical to maintaining a deployable force. Military families face unique stressors, including combat deployments,...

Early identification of complications after distal pancreatectomy splenectomy (DPS) poses challenges, as white blood cell count (WBC) is confounded by physiologic leukocytosis. We examined WBC patterns associated with complications after DPS.Clinicopathologic data were collected for patients who underwent DPS in our system from 2009 to 2016. We examined WBC, temperature, platelet count (PC), and ratios of these variables as potential early indicators of patients at risk of infections or major complications (MCs).348 patients met study inclusion, of whom 206 (59%) were women and the median patient age was 59 ± 15 years. Infectious and MC rates were 11% and 16%, respectively, with1% 30-day mortality. Postoperative WBC peaks were higher in patients with infections and MCs compared with no complication (23 vs. 17, p 0.0001). WBC peak timing occurred postoperative day (POD) 2-3 for uncomplicated cases while peaks occurred POD9 for patients with infections and MCs.These data define patterns of leukocytosis following DPS. Although differences in infection markers were identified for patients with and without complications, no obvious thresholds were identified. Clinical suspicion for complications after DPS remains our best tool for early identification.

After 43 years of dormancy, Taal Volcano violently erupted in January 2020 forming a towering eruption plume. The fall deposits covered an area of 8605 km2, which includes Metro Manila of the National Capital Region of the Philippines. The tephra fall caused damage to crops, traffic congestion, roof collapse, and changes in air quality in the affected areas. In a tropical region where heavy rains are frequent, immediate collection of data is crucial in order to preserve the tephra fall deposit record, which is readily washed away by surface water runoff and prevailing winds. Crowdsourcing, field surveys, and laboratory analysis of the tephra fall deposits were conducted to document and characterize the tephra fall deposits of the 2020 Taal Volcano eruption and their impacts. Results show that the tephra fall deposit thins downwind exponentially with a thickness half distance of about 1.40 km and 9.49 km for the proximal and distal exponential segments, respectively. The total calculated volume of erupted fallout deposit is 0.057 km3, 0.042 km3, or 0.090 km3 using the exponential, power-law, and Weibull models, respectively, and all translate to a VEI of 3. However, using a probabilistic approach (Weibull method) with 90% confidence interval, the volume estimate is as high as 0.097 km3. With the addition of the base surge deposits amounting to 0.019 km3, the volume translates to a VEI of 4, consistent with the classification for the observed height and umbrella radius of the 2020 main eruption plume. VEI 4 is also consistent with the calculated median eruption plume height of 17.8 km and sub-plinian classification based on combined analysis of isopleth and isopach data. Phreatomagmatic activity originated from a vent located in Taal Volcano’s Main Crater Lake (MCL), which contained 42 million m3 of water. This eruptive style is further supported by the characteristics of the ash grain components of the distal 12 January 2020 tephra fall deposits, consisting dominantly of andesitic vitric fragments (83–90%). Other components of the fall deposits are lithic (7–11%) and crystal (less than 6%) grains. Further textural and geochemical analysis of these tephra fall deposits contributes to better understand the volcanic processes that occurred at Taal Volcano, one of the 16 Decade Volcanoes identified by the International Association of Volcanology and Chemistry of the Earth’s Interior (IAVCEI) because of its destructive nature and proximity to densely populated areas. The crowdsourcing initiative provided a significant portion of the data used for this study while at the same time educating and empowering the community to build resilience.