scholarly journals Ulcerative Colitis and Cytomegalovirus Infection: From A to Z

2020 ◽  
Vol 14 (8) ◽  
pp. 1162-1171 ◽  
Author(s):  
Fadi H Mourad ◽  
Jana G Hashash ◽  
Viraj C Kariyawasam ◽  
Rupert W Leong
Keyword(s):  
Ulcerative Colitis ◽  
Inclusion Bodies ◽  
Antiviral Treatment ◽  
Low Grade ◽  
High Grade ◽  
Cmv Infection ◽  
Significant Difference ◽  
Cmv Colitis ◽  
Cmv Disease ◽  
Severe Colitis

Abstract Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.

Dysplastic Progression to Adenocarcinoma is Equivalent in Ulcerative Colitis and Crohn’s Disease

2020 ◽  
Author(s):  
Amy L Lightner ◽  
Sarah Vogler ◽  
John McMichael ◽  
Xue Jia ◽  
Miguel Regueiro ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Low Grade ◽  
High Grade ◽  
Surveillance Colonoscopy ◽  
Right Colon ◽  
Significant Difference ◽  
Rate Of Progression ◽  
Low Grade Dysplasia ◽  
The Right ◽  
Crohn’S Diseases

Abstract Background We sought to determine the rate of progression from dysplasia to adenocarcinoma in ulcerative colitis [UC] vs Crohn’s diseases [CD] and describe the risk factors unique to each. Methods All adult patients [≥18 years] with a known diagnosis of either UC or CD who underwent a surveillance colonoscopy between January 1, 2010 and January 1, 2020 were included. Results A total of 23 751 surveillance colonoscopies were performed among 12 289 patients between January 1, 2010 and January 1, 2020; 6909 [56.2%] had a diagnosis of CD and 5380 [43.8%] had a diagnosis of UC. There were a total of 668 patients [5.4%] with low-grade dysplasia [LGD], 76 patients [0.62%] with high-grade dysplasia [HGD], and 68 patients [0.55%] with adenocarcinoma in the series; the majority of the dysplastic events were located in the right colon. Significantly more UC patients had a dysplastic event, but the rate of LGD and HGD dysplasia progression to adenocarcinoma was not significantly different in CD or UC [p = 0.682 and p = 1.0, respectively]. There was no significant difference in the rate of progression from LGD/HGD to adenocarcinoma based on random biopsies vs targeted biopsies of visible lesions [p = 0.37]. However, the rate of progression from LGD vs HGD to adenocarcinoma was significantly greater for HGD [p < 0.001]. Conclusion While more UC patients were found to have neoplasia on colonoscopy, the rate of progression from LGD and HGD to adenocarcinoma was equivalent in UC and CD, suggesting that endoscopic surveillance strategies can remain consistent for all IBD patients.

scholarly journals Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program

2018 ◽  
Vol 143 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Barbara A. Crothers ◽  
Mohiedean Ghofrani ◽  
Chengquan Zhao ◽  
Leslie G. Dodd ◽  
Kelly Goodrich ◽  
...  
Keyword(s):  
Education Program ◽  
Repeated Measures ◽  
False Negative ◽  
Misclassification Rate ◽  
Low Grade ◽  
High Grade ◽  
Squamous Intraepithelial Lesion ◽  
Significant Difference ◽  
Intraepithelial Lesion ◽  
Diagnostic Concordance

Context.— Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. Objective.— To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. Design.— We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. Results.— There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL (P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). Conclusions.— More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.

scholarly journals Study the activity of P53 & Bcl-2 genes in the biopsies of inflamed colon from patients of ulcerative colitis

2010 ◽  
Vol 4 (1) ◽  
pp. 34-43
Author(s):  
Zainab M. T. Jafer ◽  
Esmail K. Shubber
Keyword(s):  
Ulcerative Colitis ◽  
Intermediate Stage ◽  
Hybridization Technique ◽  
Low Grade ◽  
High Grade ◽  
Colonic Tissue ◽  
Grade 3 ◽  
Apoptosis Gene ◽  
Tumor Gene

The study has been done on 36 samples of biopsies which drawn from patients suffered from ulcerative colitis, the samples were taken from female & male of different ages. The goal was to observe the gene expression of the suppresser tumor gene P53, & the suppresser apoptosis gene Bcl-2, by using in situ hybridization technique. The results showed that there were relationships between both genes (P53 & Bcl-2) in patients suffered from ulcerative colitis compared with healthy individuals. The suppresser gene P53 gave 63% in the high grade(3) , 29 % in the intermediate stage (2) & 8% in the low grade (1) .While for the suppresser apoptosis gene Bcl-2 , the results showed increasing in the activity of this gene , which gave 66% in the high grade(3) , 27% in the intermediate stage (2) , & 7% in the low grade (1) . These results indicate accumulated mutations in the gene P53 & increase in the activity of gene Bcl-2 in inflamed colonic tissue of chronic ulcerative colitis. This gave an indication of early detection for diagnostic, therapeutic and monitoring purposes.

scholarly journals Urothelial carcinoma and its association with age and gender.

2019 ◽  
Vol 26 (10) ◽  
pp. 1719-1723
Author(s):  
Rukhsana Parveen Samo ◽  
Asim Mehmood ◽  
Sana Kashif
Keyword(s):  
Urothelial Carcinoma ◽  
Male Gender ◽  
Health Science ◽  
P Value ◽  
Low Grade ◽  
High Grade ◽  
Histological Grading ◽  
Age And Gender ◽  
Significant Difference ◽  
And Gender

Objectives: To determine the urothelial carcinoma and its association with age and gender. Study Design: Retrospective study. Setting: Pathology department of Liaquat university of Medical and Health Science. Period: One year from January 2016 to December 2016. Material and Methods: Four micrometer thick paraffin-embedded and formalin-fixed sections were prepared from transurethral resection6of bladder6tumor (TURBT) samples of urothelial carcinoma patients and were examined. Histological grading was categorized as low and high grades. All the data was collected by self-made proforma. Data was analyzed by SPSS version 20. Results: Total 83 cases were enrolled in current study; their mean age was 49.19+12.33 years. Males were found in the majority 51(61.4%) and females were 32(38.6%). Most common age group was 46-60 years 36(43.4%). According to the histological grading high grade was most common as 65.10%, and low grade urothelial carcinoma was 34.90%. There was no significant difference according to age of histological grading. Male gender was most common, while progression of disease was higher among females in contrast to males as high grade carcinoma was significantly higher among females, p-value 0.014. Conclusion: It was concluded that male gender is the contributing factor of urothelial carcinoma, but disease progression significantly high among females. No significant association has been found according to age.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

A Large Cohort Analysis of CMV Viral Load and Ganciclovir-Related Neutropenia in Nonmyeloablative (NM-HCT) and Myeloablative (M-HCT) Allogeneic Hematopoietic Cell Transplant Recipients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2975-2975
Author(s):  
Hirohisa Nakamae ◽  
Katharine A. Kirby ◽  
Brenda M. Sandmaier ◽  
Lalita Norasetthada ◽  
David Maloney ◽  
...  
Keyword(s):  
Risk Factors ◽  
Viral Load ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
High Grade ◽  
Donor Age ◽  
Cmv Infection ◽  
Significant Difference ◽  
Recipient Age

Abstract Background. The “true” nonmyeloablative allogeneic stem cell transplantation (NM-HCT) allows initial establishment of mixed T-cell chimerism for up to 6 months. The prolonged presence of host memory immune response after NM-HCT may play a role in protection against CMV infection especially early after NM-HCT. Furthermore, we previously reported that the incidence and poor outcome of ganciclovir-related neutropenia (GCV-N) is strongly associated with myelotoxic conditioning. Therefore, non-myeloablative HCT may also contribute to a lower risk of GCV-N. In this to date largest cohort we examined the risk of CMV infection and GCV-N after NM conditioning. Methods. We retrospectively analyzed 537 NM-HCT recipients (median age 54.2 yrs) and 2489 M-HCT recipients (median age 39.8 yrs) transplanted between 1/1995 and 12/2005. The conditionings for NM-HCT mostly consisted of 2 Gy TBI with/without fludarabine. Post-grafting immunosuppression consisted of most commonly mycophenolate mofetil and cyclosporine (CSP) for NM-HCT recipients and methotrexate/CSP for M-HCT recipients. CMV surveillance was performed weekly by antigenemia (AG) or plasma PCR testing. GCV/VGCV was given for CMV AG/PCR positivity. We evaluatedany AG/DNA detection by day 100,AG >10/200,000 PBL or PCR> 1000 copies/ml (high-grade CMV AG/DNA) by day 100 andGCV-N defined as non-relapse-related neutropenia (ANC<500 μL) after AG/PCR positivity with ANC>1000 μL at time of viremia using multivariable Cox regression.In addition, post-engraftment neutropenia, defined as ANC<500 μL occurring after day 28 post HCT among relapse-free patients. Results. There was no significant difference in the incidence of CMV AG/DNA at any level between NM-HCT and M-HCT (39% vs.37%, HR 1.1, P=0.42). However, there was less high-grade CMV infection in NM-HCT compared to M-HCT patients (9% vs. 14%, adj. HR 0.6, P < 0.01). Risk factors for high-grade CMV infection other than M-HCT were advanced recipient age, CMV serostatus, transplantation year and acute GVHD. The incidence of GCV-N was similar between NM-HCT and M-HCT recipients (28% vs. 20%, adj. HR 1.3, P=0.27). Risk factors for GCV-N were advanced recipient age and acute GVHD. On the other hand, the incidence of post-engraftment neutropenia was higher in NM-HCT (29% vs. 13%, adj. HR 2.1, P<0.0001). Other risk factors for post-engraftment neutropenia included advanced recipient or donor age, cord blood, HLA mismatched/unrelated donor, female donor to male recipient, acute GVHD, recipient CMV seropositivity and CMV infection. Conclusion. Our results suggest that the risk of CMV reactivation is not affected by NM conditioning but that progression to higher levels of viral load is reduced. This may be due to residual host memory immunity after NM-HCT. Despite less toxic conditioning, the incidence of GCV-N in NM-HCT was similar to that in M-HCT. Notably, the incidence of post-engraftment neutropenia was more frequent in NM-HCT compared to M-HCT recipients. This may be due to higher recipient and/or donor age, lower capacity to metabolize drugs, or the use of myelotoxic co-medication such as MMF or TMP-SMX.

Cytomegalovirus (CMV) gB3 Genotype Is Associated with Acute Gvhd and CMV Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients (HSCT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1958-1958
Author(s):  
Débora de Campos Dieamant ◽  
Sandra Helena Alves Bonon ◽  
Francisco J P Aranha ◽  
Gislaine O. Duarte ◽  
Virginio C.O. Fernandes ◽  
...  
Keyword(s):  
Viral Load ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Gastrointestinal Disease ◽  
Antiviral Treatment ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Grade Ii ◽  
Cmv Disease

Abstract Abstract 1958 Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). Objectives: The goals of this study were: identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with the CMV disease, acute GVHD and overall survival. Study design: The diagnosis of active CMV infection after allogeneic HSCT was detected by Antigenemia (AGM) and/or Nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using the N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. Results: Were evaluated 63 allogeneic HSCT recipients, 49/63 patients (78%) presented active CMV infection detected by AGM and/or N-PCR, in a median time of 38 days after the transplant. The distribution of CMV gB genotypes in these 49 patients with active CMV infection was as follow: gB1, 19/49 (38.8%); gB2, 17/49 (34.7%); gB3, 3/49 (6.1%); gB4, 7/49 (14.3%) and three patients (6.1%) had mixed infection with gB1+gB3, gB1+gB4 and gB2+gB4. Acute GVHD grade II-IV occurred in 17/49 (34.7%) patients: 8/19 (gB1-42%), 1/17 (gB2 - 5.9%), 4/4 (gB3 - 100%) and 4/9 (gB4 - 44.4%). The distribution of the frequency of acute GVHD grade II-IV between the genotypes was statistically different (p=0.008). CMV disease occurred in 3/49 (6.1%) patients, characterized for gastrointestinal disease and these three patients had infection with CMV gB3 genotype. This genotype of CMV was also associated with higher viral load during antiviral treatment and worse survival. Conclusions: This study demonstrated that the frequency of active CMV infection in HSCT population was high (78%). The most prevalent genotype in patients with active CMV infection was gB1 and gB3 genotype was associated with acute GVHD grade II-IV, CMV gastrointestinal disease, higher viral load during antiviral treatment and worse survival. Disclosures: No relevant conflicts of interest to declare.

Hormonal treatment of metastatic endometrial stromal sarcoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16576-e16576
Author(s):  
K. Y. Terada ◽  
J. Davis ◽  
J. Kitayama ◽  
D. Shimizu
Keyword(s):  
Aromatase Inhibitors ◽  
Stable Disease ◽  
Progesterone Receptors ◽  
Rank Test ◽  
Low Grade ◽  
Image Analyzer ◽  
High Grade ◽  
Estrogen And Progesterone Receptors ◽  
Significant Difference

e16576 Background: Endometrial stromal sarcomas (ESS) traditionally have been classified as low grade or high grade based on mitotic activity and histologic appearance. High-grade tumors are currently referred to as undifferentiated uterine sarcomas and are not included in this series. ESS are known to have high expression of estrogen and progesterone receptors. This is a retrospective study of patients with metastatic ESS treated with hormonal therapy. Methods: Following approval by the institutional review board all patients diagnosed with ESS from 1987–2007 were identified. Clinical and demographic information were abstracted from the charts and all histologic materials were re-reviewed. Estrogen and progesterone receptor testing was performed utilizing mouse monoclonal antibodies and the Cell Analysis Systems 200 Image analyzer. Survival was calculated using the Kaplan-Meier method and comparisons utilized the log rank test. Results: Thirteen patients with ESS were identified during this period. Seven had disease confined to the uterus. Six had extrauterine disease; 5 patients presented with metastases and 1 patient presented with a pelvic recurrence 20 years following a hysterectomy. All underwent surgical resection except for 1 patient that declined surgery. All 6 patients with metastases had tumors that tested positive for estrogen and progesterone receptors; all were treated with megestrol acetate initially for a period of 1–4 years. Two patients were then changed to maintenance with medroxyprogesterone acetate. Three patients with persistent disease were changed to aromatase inhibitors; 1 to letrozole and 2 to anastrazole. One of these patients has had a complete response and 2 have had stable disease. One patient has been lost to follow-up. Follow-up for the 6 patients was 2–22 years; no known patients died of their disease. Actuarial 2- and 5-year survivals were 80% and 65%, respectively. There was no significant difference in survival between patients with metastases and without metastases. Conclusions: ESS tumors are relatively uncommon and there is an absence of studies to guide treatment of patients with metastases. This experience indicates that these tumors respond well to hormonal manipulation. Treatment with progestins or aromatase inhibitors may result in remission or stable disease. No significant financial relationships to disclose.

Prognostic value of the volume time index (VTI) ratio for patients with appendiceal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15704-e15704
Author(s):  
Josh Karpes ◽  
Daniel Dotta ◽  
Oliver Fisher ◽  
Raphael Shamavonian ◽  
Nayef Alzahrani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Peritoneal Dissemination ◽  
Tumour Volume ◽  
Peritoneal Metastases ◽  
Low Grade ◽  
High Grade ◽  
Appendiceal Cancer ◽  
Appendix Cancer ◽  
Significant Difference

e15704 Background: Completeness of cytoreduction score (CC-score) and tumour volume (as expressed by the peritoneal cancer index (PCI)) have been demonstrated as important post-operative prognostic factors in those patients with appendix cancer with peritoneal metastases undergoing CRS/HIPEC. A previous analysis included a pre-operative factor and demonstrated the tumour marker to volume index (CA19-9/PCI) in patients who had low grade appendiceal cancer with peritoneal metastases was an independent prognostic factor for overall survival (OS). This analysis aims to evaluate VTI as a prognostic factor in low- and high-grade appendix neoplasms with peritoneal dissemination managed with CRS/HIPEC. Methods: A retrospective cohort study of all patients diagnosed with appendiceal cancer with peritoneal dissemination managed with CRS/IPC from 1996 to 2017 was performed by analysing the survival effect of the ratio of tumour volume to the time between initial tumour resection and CRS/HIPEC. VTI was stratified into low versus high groups, and tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Two hundred and sixty-four patients were included. For both DPAM and PMCA, there was no statistically significant difference in overall survival between patients with a low versus high VTI. For both low and high VTI in DPAM, the median survival was not reached, p= 0.586. For PMCA, those with a low VTI had an overall survival of 63 months (95%CI 48-NR), versus those with a high VTI 69 months (95%CI 45-NR), p= 0.97. There was no statistically significant difference in the median recurrence free survival (RFS) between low and high VTI for both DPAM and PMCA. Conclusions: The volume to time ratio for appendix cancer with peritoneal dissemination was not an independent prognostic indicator for overall survival in patients undergoing CRS/HIPEC, suggesting that this index is not a valuable pre-operative planning tool.

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