Publications by authors named "Sepideh Besharati"

20 Publications

  • Page 1 of 1

Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy.

Cancer Discov 2021 Feb 25. Epub 2021 Feb 25.

Medicine, Johns Hopkins University

Colorectal cancer (CRC) is multi-faceted with subtypes defined by genetic, histological, and immunologic features which are potentially influenced by inflammation, mutagens, and/or microbiota. CRCs with activating mutations in BRAF are associated with distinct clinical characteristics though the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApc[triangle]716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL-17-dependent, distal colon adenomas. Herein, we report that addition of the BRAFV600E mutation to this model results in emergence of a distinct locus of mid-colon tumors. In ETBF-colonized BRAFV600ELgr5CreMin (BLM) mice, tumors have similarities to human BRAFV600E 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 interferon-gamma signatures, and are sensitive to anti-PDL1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in CRC pathogenesis and sensitivity to immunotherapy.
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http://dx.doi.org/10.1158/2159-8290.CD-20-0770DOI Listing
February 2021

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

Eur J Nucl Med Mol Imaging 2020 04 18;47(4):816-827. Epub 2019 Nov 18.

Department of Radiology, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, MD, USA.

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 Y 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.
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http://dx.doi.org/10.1007/s00259-019-04588-xDOI Listing
April 2020

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

Pancreas 2019 04;48(4):574-578

Shalamar Medical & Dental College, Lahore, Punjab, Pakistan.

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.
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http://dx.doi.org/10.1097/MPA.0000000000001283DOI Listing
April 2019

Multiple Immune-Suppressive Mechanisms in Fibrolamellar Carcinoma.

Cancer Immunol Res 2019 05 22;7(5):805-812. Epub 2019 Mar 22.

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

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.
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http://dx.doi.org/10.1158/2326-6066.CIR-18-0499DOI Listing
May 2019

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

J Clin Invest 2019 03 11;129(4):1699-1712. Epub 2019 Mar 11.

Bloomberg-Kimmel Institute for Immunotherapy, Departments of Oncology and Medicine and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1172/JCI124196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436866PMC
March 2019

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

Am J Clin Pathol 2019 01;151(2):226-230

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD.

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.
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http://dx.doi.org/10.1093/ajcp/aqy134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306046PMC
January 2019

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

Endoscopy 2018 05 22;50(5):497-504. Epub 2017 Dec 22.

Division of Gastroenterology, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland, United States.

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 ± 13.8 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 ( > 0.99). The sensitivity for malignancy of EUS-FNA was 82 % in the slow-pull group and 69 % in the suction group ( = 0.10). The first-pass diagnostic rate (42.6 % vs. 38.3 %;  = 0.71), acquisition of core tissue (60.6 % vs. 46.7 %;  = 0.14), and the median (range) number of passes to diagnosis (2 1 2 3 vs. 1 1 2;  = 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.
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http://dx.doi.org/10.1055/s-0043-122381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441969PMC
May 2018

MODIFIED ALVARADO SCORE IN CHILDREN WITH DIAGNOSIS OF APPENDICITIS.

Arq Bras Cir Dig 2017 Jan-Mar;30(1):51-52

Department of Pediatric Surgery, Imam Khomeini Hospital.

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.
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http://dx.doi.org/10.1590/0102-6720201700010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424688PMC
May 2018

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

Endoscopy 2016 Sep 29;48(9):802-8. Epub 2016 Jun 29.

Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1055/s-0042-108567DOI Listing
September 2016

Impact of Perioperative Phosphorus and Glucose Levels on Liver Regeneration and Long-term Outcomes after Major Liver Resection.

J Gastrointest Surg 2016 07 27;20(7):1305-16. Epub 2016 Apr 27.

Division of Surgical Oncology John L. Cameron Professor of Alimentary Surgery Department of Surgery, Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA.

Introduction: The impact of phosphorus as well as glycemic alterations on liver regeneration has not been directly examined. We sought to determine the impact of phosphorus and glucose on liver regeneration after major hepatectomy.

Methods: Early and late liver regeneration index was defined as the relative increase of liver volume (RLV) within 2[(RLV2m-RLVp)/RLVp] and 7 months[(RLV7m-RLVp)/RLVp] following surgery. The association of perioperative metabolic factors, liver regeneration, and outcomes was assessed.

Results: On postoperative day 2, 50 (52.6 %) patients had a low phosphorus level (≤2.4 mg/dl), while 45 (47.4 %) had a normal/high phosphorus level (>2.4 mg/dl). Despite comparable clinicopathologic characteristics (all P > 0.05) and RLV/TLV at surgery (P = 0.84), regeneration index within 2 months was lower in the normal/high phosphorus group (P = 0.01) with these patients having increased risk for postoperative liver failure (P = 0.01). The inhibition of liver regeneration persisted at 7 months (P = 0.007) and was associated with a worse survival (P = 0.02). Preoperative hypoglycemia was associated only with a lower early regeneration index (P = 0.02).

Conclusions: Normal/high phosphorus was associated with inhibition of early and late liver regeneration, as well as with an increased risk of liver failure and worse long-term outcomes. Immediate preoperative hypoglycemia was associated with a lower early volumetric gain. Metabolic factors may represent early indicators of liver failure that could identify patients at increased risk for worse outcomes.
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http://dx.doi.org/10.1007/s11605-016-3147-6DOI Listing
July 2016

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

Surgery 2016 07 5;160(1):81-91. Epub 2016 Apr 5.

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

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.
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http://dx.doi.org/10.1016/j.surg.2016.02.014DOI Listing
July 2016

Predictors of incomplete optical colonoscopy using computed tomographic colonography.

Saudi J Gastroenterol 2016 Jan-Feb;22(1):43-9

Department of Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Background/aims: Optical colonoscopy (OC) is the primary modality for investigation of colonic pathology. Although there is data on demographic factors for incomplete OC, paucity of data exists for anatomic variables that are associated with an incomplete OC. These anatomic variables can be visualized using computed tomographic colonography (CTC). We aim to retrospectively identify variables associated with incomplete OC using CTC and develop a scoring method to predict the outcome of OC.

Patients And Methods: In this case-control study, 70 cases ( with incomplete OC) and 70 controls (with complete OC) were identified. CTC images of cases and controls were independently reviewed by a single CTC radiologist. Demographic and anatomical parameters were recorded. Data was examined using descriptive linear statistics and multivariate logistic regression model.

Results: On analysis, female gender (80% vs 58.6% P = 0.007), prior abdominal/pelvic surgeries (51.4% vs 14.3% P < 0.001), colonic length (187.6 ± 30.0 cm vs 163.8 ± 27.2 cm P < 0.001), and number of flexures (11.4 ± 3.1 vs 8.4 ± 2.9 P < 0.001) increased the risk for incomplete OC. No significant association was observed for increasing age (P = 0.881) and history of severe diverticulosis (P = 0.867) with incomplete OC. A scoring system to predict the outcome of OC is proposed based on CTC findings.

Conclusion: Female gender, prior surgery, and increasing colonic length and tortuosity were associated with incomplete OC, whereas increasing age and history of severe diverticulosis were not. These factors may be used in the future to predict those patients who are at risk of incomplete OC.
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http://dx.doi.org/10.4103/1319-3767.173758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763528PMC
January 2017

Intraoperative measurement of esophagogastric junction cross-sectional area by impedance planimetry correlates with clinical outcomes of peroral endoscopic myotomy for achalasia: a multicenter study.

Surg Endosc 2016 07 20;30(7):2886-94. Epub 2015 Oct 20.

Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, MD, USA.

Background: Peroral endoscopic myotomy (POEM) has been introduced as an endoscopic alternative to surgical myotomy. The endoluminal functional lumen imaging probe (endoFLIP) evaluates esophagogastric junction (EGJ) distensibility based on cross-sectional area and pressure in response to volume distension. The aim of this study was to evaluate whether there is a correlation between endoFLIP measurements during POEM and postoperative clinical outcomes in terms of symptom relief and development of post-procedure reflux.

Methods: We conducted a retrospective review of achalasia patients who underwent POEM and intraoperative endoFLIP at three tertiary centers. Patients were divided into two groups based on clinical response measured by Eckardt score (ES): good response (ES < 3) or poor response (ES ≥ 3). Post-procedure reflux was defined as the presence of esophagitis and/or abnormal pH study. EGJ diameter, cross-sectional area, and distensibility measured by endoFLIP were compared.

Results: Of the 63 treated patients, 50 had good and 13 had poor clinical response. The intraoperative final EGJ cross-sectional area was significantly higher in the good-response group versus poor-response group; median (interquartile range): 89.0 (78.5-106.7) versus 72.4 (48.8-80.0) mm(2) [p = 0.01]. The final EGJ cross-sectional area was also significantly higher in patients who had reflux esophagitis after POEM: 99.5 (91.2-103.7) versus 79.3 (57.1-94.2) mm(2) [p = 0.02].

Conclusion: Intraoperative EGJ cross-sectional area during POEM for achalasia correlated with clinical response and post-procedure reflux. Impedance planimetry is a potentially important tool to guide the extent and adequacy of myotomy during POEM.
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http://dx.doi.org/10.1007/s00464-015-4574-2DOI Listing
July 2016

Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video).

Gastrointest Endosc 2015 Dec 5;82(6):1106-9. Epub 2015 Aug 5.

Division of Medicine, Department of Gastroenterology and Hepatology, Johns Hopkins Hospital, Baltimore, Maryland USA.

Background And Aims: Medical treatment options for gastroparesis are limited. Data from studies of botulinum toxin and surgical pyloroplasty suggest that disruption of the pylorus can result in symptomatic improvement in some patients with refractory gastroparetic symptoms. The aim of this study was to determine the clinical response to transpyloric stent (TPS) placement in patients with gastroparetic symptoms refractory to standard therapy.

Methods: Patients with gastroparesis refractory to medical treatment were referred for TPS placement for salvage therapy. Self-reported symptom improvement, stent migration rate, and pre- and post-stent gastric-emptying study results were collected.

Results: A total of 30 patients with refractory gastroparesis underwent 48 TPS procedures. Of these, 25 of 48 (52.1%) were performed in patients admitted to the hospital with intractable gastroparetic symptoms. Successful stent placement in the desired location across the pylorus (technical success) was achieved during 47 procedures (98%). Most (n = 24) stents were anchored to the gastric wall by using endoscopic suturing with a mean number of sutures of 2 (range 1-3) per procedure. Clinical response was observed in 75% of patients, and all inpatients were successfully discharged. Clinical success in patients with the predominant symptoms of nausea and vomiting was higher than in those patients with a predominant symptom of pain (79% vs 21%, P = .12). A repeat gastric-emptying study was performed in 16 patients, and the mean 4-hour gastric emptying normalized in 6 patients and significantly improved in 5 patients. Stent migration was least common (48%) when stents were sutured.

Conclusion: TPS placement is a feasible novel endoscopic treatment modality for gastroparesis and improves both symptoms and gastric emptying in patients who are refractory to medical treatment, especially those with nausea and vomiting. TPS placement may be considered as salvage therapy for inpatients with intractable symptoms or potentially as a method to select patients who may respond to more permanent therapies directed at the pylorus.
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http://dx.doi.org/10.1016/j.gie.2015.06.051DOI Listing
December 2015

Comprehensive analysis of efficacy and safety of peroral endoscopic myotomy performed by a gastroenterologist in the endoscopy unit: a single-center experience.

Gastrointest Endosc 2016 Jan 26;83(1):117-25. Epub 2015 Jul 26.

Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Background And Aims: The safety and efficacy of peroral endoscopic myotomy (POEM) when performed by gastroenterologists in the endoscopy unit are currently unknown. The aims of this study were to assess (1) the safety and efficacy of POEM in which all procedures were performed by 1 gastroenterologist in the endoscopy unit, and (2) the predictors of adverse events and nonresponse.

Methods: All consecutive patients who underwent POEM at 1 tertiary center were included. Clinical response was defined by a decrease in the Eckardt score to 3 or lower. Adverse events were graded according to the American Society for Gastrointestinal Endoscopy lexicon's severity grading system.

Results: A total of 60 consecutive patients underwent POEM in the endoscopy suite with a mean procedure length of 99 minutes. The mean length of submucosal tunnel was 14 cm and the mean myotomy length was 11 cm. The median length of hospital stay was 1 day. Among 52 patients with a mean follow-up period of 118 days (range 30-750), clinical response was observed in 48 patients (92.3%). There was a significant decrease in Eckardt score after POEM (8 vs 1.19, P < .0001). The mean lower esophageal sphincter pressure decreased significantly after POEM (29 mm Hg vs 11 mm Hg, P < .0001). A total of 10 adverse events occurred in 10 patients (16.7%): 7 rated as mild, 3 as moderate, and none as severe. Procedure length was the only predictor of adverse events (P = .01). pH impedance testing was completed in 25 patients, and 22 (88%) had abnormal acid exposure, but positive symptom correlation was present in only 6 patients. All patients with symptomatic reflux were successfully treated with proton pump inhibitors.

Conclusions: POEM can be effectively and safely performed by experienced gastroenterologists at a tertiary care endoscopy unit. Adverse events are infrequent, and most can be managed intraprocedurally. Post-POEM reflux is frequent but can be successfully managed medically.
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http://dx.doi.org/10.1016/j.gie.2015.06.013DOI Listing
January 2016

Intraprocedural fluoroscopy to determine the extent of the cardiomyotomy during per-oral endoscopic myotomy (with video).

Gastrointest Endosc 2015 14;81(6):1451-6. Epub 2015 Apr 14.

Department of Medicine and Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Background: An adequate myotomy on the gastric side is considered essential to optimize outcomes in patients undergoing per-oral endoscopic myotomy (POEM). An objective method to measure the length of gastric myotomy has not yet been reported.

Objective: To evaluate a new method of precisely determining the length of the submucosal tunnel below the esophagogastric junction (EGJ) using intraprocedural fluoroscopy.

Design: Single-center cohort study.

Setting: Academic tertiary care center.

Patients: Twenty-four consecutive patients who underwent POEM for management of achalasia.

Interventions: A radiopaque marker (endoscopic clip placed at the EGJ or fluoroscopically guided placement of a 19-gauge needle on the skin) was used to mark the EGJ. The endoscope was inserted to the most distal aspect of the submucosal tunnel and, using fluoroscopy, the distance between the radiopaque marker and the tip of the endoscope was measured.

Main Outcome Measurements: Technical success, procedural impact, duration of technique, and adverse events.

Results: Technical success was achieved in 100% of patients. The submucosal tunnel was extended in 5 patients (20.8%) with a mean extension of 1.4±.5 cm. The mean increase in procedure time was 4 minutes with the endoscopic clip and 2 minutes with the 19-gauge needle. There were no adverse events associated with this technique.

Limitations: Need for fluoroscopy. Absence of available criterion standard.

Conclusions: Intraprocedural fluoroscopy was an efficient and safe method of objectively documenting the extent of gastric myotomy during POEM. This may benefit those investigating the anatomic and physiologic changes that occur during the myotomy and those early in their experience performing POEM.
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http://dx.doi.org/10.1016/j.gie.2015.01.052DOI Listing
April 2016

Intraoperative determination of the adequacy of myotomy length during peroral endoscopic myotomy (POEM): the double-endoscope transillumination for extent confirmation technique (DETECT).

Endoscopy 2015 Oct 7;47(10):925-8. Epub 2015 Apr 7.

Department of Medicine and Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Background And Study Aims: Precise identification of the gastroesophageal junction (GEJ) is a challenging prerequisite for adequate length of an esophageal myotomy. Multiple standard methods to identify the GEJ have been described; however, a more objective modality is needed to ensure effective peroral endoscopic myotomy (POEM).

Patients And Methods: In the double-endoscope transillumination for extent confirmation technique (DETECT), an ultraslim gastroscope is passed to the most distal aspect of the submucosal tunnel created during POEM. A regular gastroscope is advanced into the stomach, and the visualization of transillumination from the ultraslim gastroscope enables identification of the extent of the submucosal tunnel.

Results: A total of 10 patients underwent POEM with DETECT. Initial submucosal tunneling was performed based on a determination of the GEJ location via standard methods. DETECT indicated the tunnel extent to be inadequate in 50% of patients, and the tunnel was extended a further 1 to 2cm. The mean initial tunnel length was 15.4cm, with a mean initial myotomy length of 11.9cm. DETECT was performed in less than 10 minutes without complications.

Conclusion: DETECT is an objective method for determining the adequacy of the submucosal tunnel length during POEM.
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http://dx.doi.org/10.1055/s-0034-1391900DOI Listing
October 2015

Snare-over-scope technique for retrieval of a proximally migrated biliary stent.

Endoscopy 2014 19;46 Suppl 1 UCTN:E650-1. Epub 2014 Dec 19.

Department of Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, United States.

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http://dx.doi.org/10.1055/s-0034-1390847DOI Listing
September 2015

Distribution of renal histopathology in Guilan: a single-center report.

Iran J Kidney Dis 2012 May;6(3):173-7

Department of Internal Medicine, Guilan University of Medical Sciences, Rasht, Iran.

Introduction: Glomerulonephritis is the third most common cause of end-stage renal disease. Epidemiological data of kidney disease is population-based and has great geographic variability. The aim of this study was to assess the results of all kidney biopsies in a 5-year period in the Guilan province.

Materials And Methods: In a retrospective study of 336 kidney biopsies recorded in the Department of Nephrology in Razi Hospital of Rasht, capital city of Guilan province, from August 2001 to September 2006, data consisting of age, gender, indication of kidney biopsy, and histopathological diagnosis were collected and analyzed.

Results: A total of 336 kidney biopsies were reviewed (73.8% males; mean age, 40.12 ± 16.78 years). Nephritic syndrome (42.5%) and nephrotic syndrome (38.7%) were the most frequent indications of biopsy. Overall, pathologic examinations were indicative of glomerulonephritis in 272 (81.0%) biopsies and nonglomerular diseases in 64 (19.0%). The most common cause of secondary glomerulonephritis was lupus nephritis (82.6%). Focal and segmental glomerusclerosis (20.5%) was the most common pathologic diagnosis, followed by membranous glomerulonephritis (14.9%), minimal change disease (11.6%), tubulointerstitial nephritis (8.9%), and IgA nephropathy (3.6%). The most common pathologic finding among glomerular diseases was focal segmental glomerusclerosis (25.4%), while tubulointerstitial nephritis (46.9%) was the most common among nonglomerular diseases, followed by diffuse glomerulosclerosis, interstitial fibrosis, and tubular atrophy indicative of end-stage renal disease (23.4%).

Conclusions: In our study, FSGS was the most common pathologic finding in kidney biopsies, and the frequency of IgA nephropathy was much lower than that in other studies.
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May 2012