Iliac Artery-Inferior Vena Cava-Duodenal Fistula: An Unusual Cause of Massive Gastrointestinal Bleeding.

An arteriovenous-enteric fistula is a 3-way connection between the vascular and enteric system and associated with high mortality. We describe a case of iliac artery-inferior vena cava-duodenal fistula in a young female with a retroperitoneal mass presenting with sepsis and hemorrhagic shock with a catastrophic clinical course. These fistulas can be missed on endoscopy/colonoscopy and are usually diagnosed on computed tomography angiogram of the abdomen. Complex vasculoenteric fistula should be among differentials in patients presenting with gastrointestinal bleeding, especially with a history of malignancy, radiation, foreign bodies, and trauma. The management is complex and should involve a multidisciplinary approach involving vascular surgery, intervention radiology, and gastroenterologist.

GAT107-mediated α7 nicotinic acetylcholine receptor signaling attenuates inflammatory lung injury and mortality in a mouse model of ventilator-associated pneumonia by alleviating macrophage mitochondrial oxidative stress via reducing MnSOD-S-glutathionylation.

Supraphysiological concentrations of oxygen (hyperoxia) can compromise host defense and increase susceptibility to bacterial and viral infections, causing ventilator-associated pneumonia (VAP). Compromised host defense and inflammatory lung injury are mediated, in part, by high extracellular concentrations of HMGB1, which can be decreased by GTS-21, a partial agonist of α7 nicotinic acetylcholine receptor (α7nAChR). Here, we report that a novel α7nAChR agonistic positive allosteric modulator (ago-PAM), GAT107, at 3.3 mg/kg, i.p., significantly decreased animal mortality and markers of inflammatory injury in mice exposed to hyperoxia and subsequently infected with Pseudomonas aeruginosa. The incubation of macrophages with 3.3 µM of GAT107 significantly decreased hyperoxia-induced extracellular HMGB1 accumulation and HMGB1-induced macrophage phagocytic dysfunction. Hyperoxia-compromised macrophage function was correlated with impaired mitochondrial membrane integrity, increased superoxide levels, and decreased manganese superoxide dismutase (MnSOD) activity. This compromised MnSOD activity is due to a significant increase in its level of glutathionylation. The incubation of hyperoxic macrophages with 3.3 µM of GAT107 significantly decreases the levels of glutathionylated MnSOD, and restores MnSOD activity and mitochondrial membrane integrity. Thus, GAT107 restored hyperoxia-compromised phagocytic functions by decreasing HMGB1 release, most likely via a mitochondrial-directed pathway. Overall, our results suggest that GAT107 may be a potential treatment to decrease acute inflammatory lung injury by increasing host defense in patients with VAP.

Effect of cigarette smoking on serum anti-Mullerian hormone and antral follicle count in women seeking fertility treatment: a prospective cross-sectional study.

OBJECTIVES: The relationship between smoking and ovarian reserve markers is inconclusive. The primary objective of our study was to assess the effect of cigarette smoking on the quantitative ovarian reserve parameters, serum anti-Mullerian hormone (AMH) and antral follicle count (AFC) as relevant to prediction of fertility outcomes in women seeking fertility treatment. Our secondary aims were to validate self-reported smoking behaviour using biomarkers and evaluate the association between biomarkers of ovarian reserve (serum AMH and AFC) with biomarkers of smoking exposure (breath carbon monoxide (CO) and urine cotinine levels). DESIGN: Prospective, cross-sectional study. SETTING: Single tertiary care fertility centre. PARTICIPANTS: Women ≤35 years seeking fertility treatment. PRIMARY OUTCOME MEASURES: Serum AMH and AFC. RESULTS: Significant differences were found among current smokers, ex-smokers and never smokers for breath CO (F(2,97)=33.32, p<0.0001) and urine cotinine levels (p<0.001). However, no significant differences were found either for serum AMH (F(2,91)=1.19, p=0.309) or total AFC (F(2,81)=0.403, p=0.670) among the three groups. There was no significant correlation between pack years of smoking and serum AMH (r=-0.212, n=23, p=0.166) or total AFC (r=-0.276, n=19, p=0.126). No significant correlation was demonstrated between breath CO and serum AMH (r=0.082, n=94, p=0.216) or total AFC (r=0.096, n=83, p=0.195). Similarly, no significant correlation was demonstrated between urine cotinine levels and serum AMH (r=0.146, n=83, p=0.095) or total AFC (r=-0.027, n=77, p=0.386). CONCLUSION: We did not find a statistically significant difference in quantitative ovarian reserve markers between current smokers, ex-smokers and never smokers which would be clinically meaningful in our study population. We confirmed that self-reported smoking correlates well with quantitatively measured biomarkers of smoking. This validated the self-reported comparison groups to ensure a valid comparison of outcome measures. There was no significant association between biomarkers of smoking and biomarkers of ovarian reserve. We were also unable to demonstrate a correlation between the lifetime smoking exposure and ovarian reserve.

RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels having many functions including inflammation control, as part of the cholinergic anti-inflammatory pathway. Genome wide association studies implicated RIC3, a chaperone of nAChRs, in multiple sclerosis (MS), a neuroinflammatory disease. To understand the involvement of RIC3 in inflammatory diseases we examined its expression, regulation, and function in activated immune cells. Our results show that immune activation leads to dynamic changes in RIC3 expression, in a mouse model of MS and in human lymphocytes and macrophages. We also show similarities in the expression dynamics of RIC3 and CHRNA7, encoding for the α7 nAChR subunit. Homomeric α7 nAChRs were shown to mediate the anti-inflammatory effects of cholinergic agonists. Thus, similarity in expression dynamics between RIC3 and CHRNA7 is suggestive of functional concordance. Indeed, siRNA mediated silencing of RIC3 in a mouse macrophage cell line eliminates the anti-inflammatory effects of cholinergic agonists. Furthermore, we show increased average expression of RIC3 and CHRNA7 in lymphocytes from MS patients, and a strong correlation between expression levels of these two genes in MS patients but not in healthy donors. Together, our results are consistent with a role for RIC3 and for the mechanisms regulating its expression in inflammatory processes and in neuroinflammatory diseases.

Survival Trends for Resectable Pancreatic Cancer Using a Multidisciplinary Conference: the Impact of Post-operative Chemotherapy.

PURPOSE: Despite advances in various treatment modalities, surgical resection for pancreatic ductal adenocarcinoma (PDA) remains the only curative treatment. Data remains limited regarding survival rates for resectable PDA when managed by a multidisciplinary pancreas conference (MDPC). The aim of this study is to assess survival rates, identify significant predictors of mortality, and assess the benefits of adjuvant chemotherapy for resectable PDA following presentation at a MDPC. METHODS: All patients presented from April 2013 to August 2016 with resectable PDA were discussed at a MDPC at a tertiary care center and were followed prospectively until November 2017. Survival analysis was performed using Kaplan-Meier for age, tumor size, tumor differentiation, T-stage, lymph node status, and completion of adjuvant chemotherapy cycles. Independent predictors of survival were determined using multivariate Cox regression modeling. RESULTS: After MDPC consensus and exclusions, total of 64 patients underwent successful surgery. Amongst this cohort, 1-, 2-, and 3-year survival was 78.13%, 46.30%, and 27.27%, respectively. A total of 37 patients (58%) initiated and 16 patients (25%) finished chemotherapy following surgery. Log-rank analysis revealed that tumor size, age, surgical margins, lymph node status, and number of adjuvant chemotherapy cycles received significantly influenced post-operative survival. Tumor size (p < 0.001), lymph node status (p = 0.035), and number of adjuvant chemotherapy cycles (p = 0.041) remained significant after multivariate Cox regression model. CONCLUSIONS: Our results suggest that patients with PDA with tumor size > 50 mm and/or lymph node involvement have poor outcomes despite being surgically resectable. Successful completion of adjuvant chemotherapy has better survival outcomes as compared with incomplete or no adjuvant chemotherapy. The role of alternative management such as down-staging with neoadjuvant therapy should be considered.

Distal Ileal Ulcers as Gastrointestinal Manifestation of Waldenstrom Macroglobulinemia.

Waldenstrom macroglobulinemia (WM) is a neoplastic disorder of the B-cell lymphoid system. A 69-year-old man with WM presented with diarrhea for 6 months. Magnetic resonance enterography showed thickening of the terminal ileum (TI). Colonosocopy with TI intubation showed a single TI ulcer, and small bowel enteroscopy revealed multiple ulcers in the TI. Biopsies from both were negative on hematoxylin and eosin staining. Immunoglobulin M immunofluorescence staining of the ulcers was positive for IgM deposits consistent with WM. After 6 cycles of chemotherapy with bendamustine and rituximab, symptoms resolved.

Defining Pancreatitis as a Risk Factor for Pancreatic Cancer: The Role, Incidence, and Timeline of Development.

OBJECTIVES: Acute and/or chronic pancreatitis has been implicated as an important risk factor for pancreatic cancer; however, the incidence and temporal relationship of pancreatitis before pancreatic cancer diagnosis are unclear. We aim to understand the role and incidence of pancreatitis temporally with the development of pancreatic cancer. METHODS: A population-based study was used to investigate a temporal relationship between pancreatitis and pancreatic cancer diagnoses. Intervals of 3, 6, 12, 24, and 36 months were developed. Demographical data including age, sex, and race were also recorded and analyzed. RESULTS: A total of 50,080 patients were found to have a diagnosis of pancreatic cancer, of which 7420 (14.8%) had prior diagnoses of pancreatitis. Of those, 92% were between the ages of 40 and 89 years. African Americans had a higher rate of pancreatitis before cancer diagnosis when compared with whites (21.2% vs 14.8%, P < 0.0001). Further analysis revealed that pancreatitis occurred in 81.3% of patients 3 months before a diagnosis of pancreas cancer and 98.9% had established diagnoses of pancreatic cancer within 3 years. CONCLUSIONS: Screening of patients older than 40 years who have pancreatitis and unclear etiology of pancreatitis may be warranted, especially in African Americans and male individuals.

Time to Adjuvant Systemic Therapy Following Pancreatic Cancer Resection and Effect on Outcome.

OBJECTIVES: The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy postresection and correlated with outcome. METHODS: We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy. Receiver operator curve analysis identified an interval of 66 days as the a priori value for largest discrepancy in outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively (>66 days). Propensity matching was performed to account for indication bias. RESULTS: In total, 6873 and 3348 patients received chemotherapy before and after the 66-day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, white race, and treatment after 2009. Propensity-matched median survival was 21.8 months for all patients, and of these, 6462 were stage 1. Five-year survival was 20% in patients receiving chemotherapy within 66 days and 18% in those not (P = 0.0266). In stage 1 patients, 5-year survival was 23% versus 21% (P = 0.0116) in favor of expedited chemotherapy. CONCLUSIONS: The present propensity-matched analysis showed a significant association with survival for earlier delivery of chemotherapy in the adjuvant setting.

Endoscopic ultrasound guided fine-needle aspiration vs core needle biopsy for solid pancreatic lesions: Comparison of diagnostic accuracy and procedural efficiency.

BACKGROUND: Endoscopic ultrasound (EUS) guided core needle biopsies (CNB) are increasingly being performed to diagnose solid pancreatic lesions. However, studies have been conflicting in terms of CNB improving diagnostic accuracy and procedural efficiency vs fine-needle aspiration (FNA), which this study aims to elucidate. METHODS: Data were prospectively collected on consecutive patients with solid pancreatic or peripancreatic lesions at a single tertiary care center from November 2015 to November 2016 that underwent either FNA or CNB. Patient demographics, characteristics of lesions, diagnostic accuracy, final and follow-up pathology, use of rapid on-site evaluation (ROSE), complications, and procedure variables were obtained. RESULTS: A total of 75 FNA and 48 CNB were performed; of these, 13 patients had both. Mean passes were lower with CNB compared to FNA (2.4 vs 2.9, P = .02). Use of ROSE was higher for FNA (97.3% vs 68.1%, P = .001). Mean procedure time was shorter with CNB (34.1 minutes vs 51.2 minutes, P = .02) and diagnostic accuracy was similar (89.2% vs 89.4%, P = .98). There was no difference in diagnostic accuracy when ROSE was performed for CNB vs not performed (93.5% vs 85.7%, P = .58). Additionally, diagnostic accuracy of combined FNA and CNB procedures was 92.3%, which was comparable to FNA (P = .73) or CNB (P = .52) alone. CONCLUSION: FNA and CNB had comparable safety and diagnostic accuracy. Use of CNB resulted in less number of passes and shorter procedure time as compared to FNA. Moreover, diagnostic accuracy for CNB with or without ROSE was similar.

The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal.

Various antitumor drugs, including paclitaxel, frequently cause chemotherapy-induced peripheral neuropathy (CIPN) that can be sustained even after therapy has been completed. The current work was designed to evaluate R-47, an α7 nAChR silent agonist, in our mouse model of CIPN. R-47 was administered to male C57BL/6J mice prior to and during paclitaxel treatment. Additionally, we tested if R-47 would alter nicotine's reward and withdrawal effects. The H460 and A549 non-small cell lung cancer (NSCLC) cell lines were exposed to R-47 for 24-72 h, and tumor-bearing NSG mice received R-47 prior to and during paclitaxel treatment. R-47 prevents and reverses paclitaxel-induced mechanical hypersensitivity in mice in an α7 nAChR-dependent manner. No tolerance develops following repeated administration of R-47, and the drug lacks intrinsic rewarding effects. Additionally, R-47 neither changes the rewarding effect of nicotine in the Conditioned Place Preference test nor enhances mecamylamine-precipitated withdrawal. Furthermore, R-47 prevents paclitaxel-mediated loss of intraepidermal nerve fibers and morphological alterations of microglia in the spinal cord. Moreover, R-47 does not increase NSCLC cell viability, colony formation, or proliferation, and does not interfere with paclitaxel-induced growth arrest, DNA fragmentation, or apoptosis. Most importantly, R-47 does not increase the growth of A549 tumors or interfere with the antitumor activity of paclitaxel in tumor-bearing mice. These studies suggest that R-47 could be a viable and efficacious approach for the prevention and treatment of CIPN that would not interfere with the antitumor activity of paclitaxel or promote lung tumor growth.

A Case of Secondary Sclerosing Cholangitis in the setting of Non-Hodgkin's Lymphoma.

Sclerosing cholangitis represents a spectrum of cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts. A 67-year-old Caucasian female with a history of breast cancer in remission, presented with jaundice and an exophytic mass at the base of the tongue. Laboratory data revealed cholestasis with alkaline phosphatase 953 U/L, total bilirubin 7.7 mg/dL, direct bilirubin 6.4 mg/dL, and gamma-glutamyltransferase 3369 U/L. Computed tomography (CT) scan showed widespread lymphadenopathy in the chest, abdomen, and pelvis concerning for lymphoma, acute pancreatitis and biliary dilation with hyperenhancement of the common bile duct wall. Diffuse intrahepatic biliary ductal dilatation and narrowing with multifocal stenosis of the proximal and distal aspects of the common bile duct was seen on magnetic resonance cholangiopancreatography (MRCP). Findings were consistent with sclerosing cholangitis. Pathology of the oral lesion revealed activin receptor-like kinase 1 (ALK1) positive anaplastic large cell lymphoma. Chemotherapy was initiated with cyclophosphamide, doxorubicin, adriamycin, vincristine, etoposide, and prednisone (CHOEP-14) regimen, which resulted in significant clinical improvement along with a remarkable decrease in the liver function tests. Non-Hodgkin's lymphoma (NHL) has only rarely been reported in the literature as a cause of secondary sclerosing cholangitis, i.e., only 0.2% to 2.0% of patients with NHL present with biliary tract obstruction. It is essential for gastroenterologists, oncologists, and radiologists to recognize sclerosing cholangitis occurring secondary to a systemic disease because early initiation of treatment can improve clinical outcome, as manifested by our case.

Performance of a Multidisciplinary Pancreatic Cancer Conference in Predicting and Managing Resectable Pancreatic Cancer.

OBJECTIVES: Surgery is the curative treatment for pancreatic ductal adenocarcinoma (PDA). Guidelines recommend utilizing a multidisciplinary pancreatic cancer conference (MDPC) in treatment; however, data are limited. The objective of this study was to assess the accuracy of an MDPC. METHODS: Patients with PDA presented at an MDPC were prospectively collected from April 2013 to August 2016. Patients were included if the MDPC predicted them to have resectable PDA and underwent upfront surgery. Secondary aims were to compare differences in tumor characteristics, time to surgery, and resection rates with patients prior to MDPC implementation (pre-MDPC). RESULTS: A total of 278 patients were presented at the MDPC. After excluding borderline and nonresectable cases, 91 patients were predicted as resectable on evaluation, and 70 were fit for surgery. The MDPC predicted resection in 91.4%. The MDPC had larger tumor size (32.6 vs 24.0 mm), greater proportion of stage II tumor, and a shorter time from diagnosis to resection (27.3 vs 35.5 days) compared with the pre-MDPC. Microscopically negative resections were similar between MDPC and pre-MDPC (85.9% vs 88.0%) despite advanced tumor size and stage. CONCLUSIONS: The MDPC demonstrates a high resection rate. Compared with a pre-MDPC, MDPC provides shorter time to surgery and selects for advanced tumors.

Fluoroscopy Dose and Time Characteristics During Endoscopic Retrograde Cholangiopancreatography (ERCP).

Radiation exposure during endoscopic retrograde cholangiopancreatography is known, however, data in relation to radiation usage is unclear. We evaluate radiation exposure using fluoroscopy dose (FD) and time (FT). A prospective analysis of 197 patients undergoing endoscopic retrograde cholangiopancreatography was completed. Univariate and multivariate analyses were performed to determine characteristics associated with higher FD and FT. The mean FT was 307 seconds; the mean FD was 16.5 centigray. On univariate and multivariate analysis, indication of common bile duct stricture and pancreatic stricture, interventions including dilation and the use of plastic stents placement, procedures that were moderately or very difficult, and procedures that used magnification and high-resolution images were associated with higher FD± and longer FT. Indications of common bile duct stricture and pancreatic stricture as well as interventions of dilation, plastic stents placement, and procedures that are moderately or very difficult, involve high-resolution image leading to a higher radiation exposure. Special care should be considered in these settings.

Incidence and risk factors for post-operative mortality, hospitalization, and readmission rates following pancreatic cancer resection.

BACKGROUND: The only potentially curative approach for pancreatic cancer is surgical resection, but this technically challenging procedure carries risks for postoperative morbidities and mortality. This study of a large, contemporary national database illustrates incidences of, and risk factors for, post-procedural mortality, prolonged hospital stay, and 30-day readmission. METHODS: From the National Cancer Database (NCDB), stage I-III pancreatic adenocarcinomas were identified [2004-2015]. Surgical techniques included pancreaticoduodenectomy, partial pancreatectomy (selective removal of the pancreatic body/tail), total pancreatectomy (removal of the entire pancreas) with or without subtotal resection of the duodenum and/or stomach, and extended pancreatectomy. Predictors of 30/90-day post-operative mortality, 30-day readmission rates, and prolonged hospital stay (>17 days per receiver operating curve analysis) were identified via multivariable logistic regression. RESULTS: Overall, 24,798 patients were analyzed (median age of 66). The majority of cases were T3 (47%), N0 (65%), pancreatic head lesions (83%), and treated with pancreaticoduodenectomy (57%). Only 16% received neoadjuvant therapy. Overall unadjusted risk of 30- and 90-day mortality ranged from 1.3-2.5% and 4.1-7.1%, respectively, depending on extent of surgery. Independent predictors of 30-/90-day mortality included preoperative therapy, increasing age, higher comorbidity score, lower income, case volume, and more extensive surgery. Similar findings were demonstrated regarding prolonged hospital stay and 30-day readmission. Age ≥70 was most associated with 30-day mortality, whereas age ≥60 was most associated with 90-day mortality and prolonged hospital stay. CONCLUSIONS: Quantitation of incidences and risk factors for postoperative outcomes following resection for pancreatic cancer is essential for judicious patient selection and shared decision-making between providers and patients.

SHOX haploinsufficiency presenting with isolated short long bones in the second and third trimester.

Haploinsufficiency of the transcription factor short stature homeobox (SHOX) manifests as a spectrum of clinical phenotypes, ranging from disproportionate short stature and Madelung deformity to isolated short stature. Here, we describe five infants with molecularly confirmed diagnoses of SHOX haploinsufficiency who presented in utero with short long bones during routine antenatal scanning from as early as 19 weeks gestation. Other foetal growth parameters were normal. The molecular basis of SHOX haploinsufficiency was distinct in each case. In four cases, SHOX haploinsufficiency was inherited from a previously undiagnosed parent. In our de novo case, SHOX haploinsufficiency reflected the formation of a derivative sex chromosome during paternal meiosis. Final adult height in the SHOX-deficient parents ranged from -1.9 to -1.2 SDS. All affected parents had disproportionately short limbs and two affected mothers had bilateral Madelung deformity. To our knowledge, SHOX haploinsufficiency has not previously been reported to present in utero. Our experience illustrates that SHOX deficiency should form part of the differential diagnosis of foetal short long bones and suggests a low threshold for genetic testing. This should be particularly targeted at, but not limited to, families with a history of features suggestive of SHOX deficiency. Data on the postnatal growth of our index cases is presented which demonstrates that antenatal presentation of SHOX haploinsufficiency is not indicative of severe postnatal growth restriction. Early identification of SHOX deficiency will enable accurate genetic counselling reflecting a good postnatal outcome and facilitate optimal initiation of growth hormone therapy.

Clostridium difficile extraintestinal abscess: a rare complication.

Extraintestinal Clostridium difficile is rare. A 74-year-old man with a history of ulcerative colitis presented after a fall. Trauma work-up showed liver cirrhosis. Two days later he developed abdominal pain, distension, diarrhoea and leucocytosis. Stool tested positive for C. difficile CT abdomen showed pancolitis with toxic megacolon. Total abdominal colectomy and ileostomy with a rectal stump was performed. He was discharged, but was readmitted with sepsis. CT abdomen showed a 10.4×7.2 cm fluid collection in the pelvis. C. difficile stool was negative. CT-guided abscess drainage grew C. difficile Barium enema was negative for communication from the rectal stump to the abscess. The patient was treated with metronidazole for 2 weeks. In summary, extraintestinal C. difficile can develop from recent antibiotics use, gastrointestinal surgery and microperforations from toxic megacolon. We recommend abscess drainage, concomitant treatment with metronidazole and or vancomycin, and reimaging of abscess location 2-4 weeks after cessation of antibiotics.

Phenotypic variation in anti-Mullerian hormone (AMH) production per follicle in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian morphology (PCOM): an observational cross-sectional study.

This observational study compares the ratio of serum anti-Mullerian hormone (AMH) to the total antral follicle count (AFC) (as a marker of AMH production per follicle) in the various phenotypes of women with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian morphology (PCOM). Two hundred and sixty-two women were recruited. Women with PCOS were divided into four phenotypes based on the diagnostic inclusion criteria of oligo-anovulation (OA), hyperandrogenism (HA) and polycystic ovarian morphology (PCOM). These included Group A (OA + HA + PCOM), Group B (OA + HA), Group C (HA + PCOM) and Group D (OA + PCOM). A ratio of serum AMH to total AFC was calculated and expressed as the AMH/AFC ratio which was compared in the phenotypes of PCOS and isolated PCOM. The median AMH/AFC ratios in PCOS-A, PCOS-D, PCOS-C and PCOM were 1.5, 1.6, 1.2 and 1.1, respectively. There were significant differences in the groups compared [F(3, 238) = 6.14, p = 0.000)]. The ratios were significantly higher in the oligo-anovulatory phenotypes PCOS-A and PCOS-D than the PCOM (p = 0.004 and 0.002, respectively). There was no significant difference in the ratio between ovulatory phenotype PCOS-C and PCOM (p = 0.59). The role of androgens and LH in per-follicle AMH production remains limited. The findings support the hypothesis of a key role for AMH in the mechanism of anovulation in PCOS.

Ocular Radiation Threshold Projection Based off of Fluoroscopy Time During ERCP.

OBJECTIVES: Current international guidelines for ocular radiation exposure suggest a threshold of 20 millisieverts (mSv)/year. Although endoscopists wear lead aprons, use of protective eye wear is optional. This study was conducted to analyze the lens radiation exposure during endoscopic retrograde cholangiopancreatography (ERCP) for endoscopists to determine the time of fluoroscopy needed to warrant using lens protection during ERCP. METHODS: ERCP patients were prospectively enrolled. Indications, interventions, fluoroscopy time, dose, and attending ± fellow involvement were recorded. Radiation exposure was collected from body dosimeters and dosimeters placed between the eyes. Cumulative radiation doses were obtained at study completion and averaged over the total fluoroscopy time to determine the mSv/hour exposure. RESULTS: A total of 187 cases were included. Attendings and fellows wore lens dosimeters in 178 and 126 cases, respectively, and body dosimeters in 174 and 128 cases, respectively. Attendings and fellows wore lens dosimeters throughout 15.89 and 11.24 h of fluoroscopy, respectively. The cumulative radiation dose absorbed per lens dosimeters was 5.35 mSv for attendings and 2.55 mSv for fellows. The projected lens absorption by the body dosimeters was 19.03 mSv for attendings and 5.21 mSv for fellows. The hourly fluoroscopy lens exposure was 0.34 mSv/hour for attendings and 0.23 mSv/hour for fellows. CONCLUSIONS: The amount of fluoroscopy hours needed to reach the currently suggested lens threshold limit (20 mSv/year) was 59.41 h for attendings and 88.17 h for fellows. Radioprotective eye wear should be worn by physicians with yearly fluoroscopy times in similarly structured practices that meet or exceed these thresholds.

Targeting of Micelles and Liposomes Loaded with the Pro-Apoptotic Drug, NCL-240, into NCI/ADR-RES Cells in a 3D Spheroid Model.

PURPOSE: To develop transferrin (Tf)-targeted delivery systems for the pro-apoptotic drug, NCL-240, and to evaluate the efficacy of this delivery system in ovarian cancer NCI/ADR-RES cells, grown in vitro in a 3D spheroid model. METHODS: Tf-targeted PEG-PE-based micellar and ePC/CHOL-based liposomal delivery systems for NCL-240 were prepared. NCI/ADR-RES cells were used to generate spheroids by a non-adhesive liquid overlay technique. Spheroid growth and development were monitored by size (diameter) analysis and H&E staining. The targeted formulations were compared to untargeted ones in terms of their degree of spheroid association and penetration. A cell viability analysis with NCL-240-loaded micelles and liposomes was performed to assess the effectiveness of Tf-targeting. RESULTS: Tf-targeted polymeric micelles and Tf-targeted liposomes loaded with NCL-240 were prepared. NCI/ADR-RES cells generated spheroids that demonstrated the presence of a distinct necrotic core along with proliferating cells in the spheroid periphery, partly mimicking in vivo tumors. The Tf-targeted micelles and liposomes had a deeper spheroid penetration as compared to the untargeted delivery systems. Cell viability studies using the spheroid model demonstrated that Tf-mediated targeting markedly improved the cytotoxicity profile of NCL-240. CONCLUSION: Transferrin targeting enhanced delivery and effectiveness of micelles and liposomes loaded with NCL-240 against NCI/ADR-RES cancer cells in a 3D spheroid model.