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International Journal of Gynecological... Mar 2018Literature published between 1975 and 2015 was systematically reviewed to conduct a case-comparator study of tissue based, immunohistochemical biomarker expression among... (Review)
Review
Literature published between 1975 and 2015 was systematically reviewed to conduct a case-comparator study of tissue based, immunohistochemical biomarker expression among malignant glandular histotypes of the uterine cervix so as to identify differences that could have diagnostic utility. Of the 902 abstracts, 154 articles had a full review, and 52 were included. Biomarker positivity in cases of adenocarcinoma in situ (AIS) were compared with atypical lobular endocervical glandular hyperplasia and invasive histotypes grouped as mucinous, endometrioid, adenosquamous, serous clear cell, minimal deviation-gastric type, and mesonephric carcinomas (7 AIS case-comparators). The invasive histotypes were compared with each other (30 adenocarcinoma case-comparators). Biomarker positivity in all 37 case-comparators was calculated as weighted averages of histotype-specific estimates. Unsupervised hierarchical clustering examined differences in expression and were visualized via heatmaps and dendrograms. Of the 56 biomarkers tested, 1 or more of 15 showed a 50% or more difference in positive expression in 6 (86%) of the AIS and 21 (70%) of the adenocarcinoma case-comparators. There was no data on the comparison of serous clear cell to mesonephric carcinoma. AIS case-comparator biomarkers were HIK1083, alpha SMA, PAX8, VIL1, CEA, p53, p16, and CD10, and only alpha SMA had a difference of 100%. The adenocarcinoma case-comparator biomarkers were CEA, p53, Claudin18, HIK1083, p16, Calretinin, CD10, PR, Chromogranin, MUC6, Vimentin and p63, and none had a difference of 100%. Biomarker expression in the discrimination of AIS from invasive adenocarcinoma, and the invasive histotypes from each other is understudied. One or more of 15 biomarkers could have diagnostic utility.
Topics: Adenocarcinoma in Situ; Biomarkers; Cervix Uteri; Female; Humans; Immunohistochemistry; Neoplasms, Glandular and Epithelial; Uterine Cervical Neoplasms
PubMed: 28582347
DOI: 10.1097/PGP.0000000000000406 -
International Journal of Gynecological... May 2017Overall, patients with mucinous ovarian carcinoma (MOC) are considered to have a better prognosis compared with the whole group of nonmucinous carcinomas. However, some... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Overall, patients with mucinous ovarian carcinoma (MOC) are considered to have a better prognosis compared with the whole group of nonmucinous carcinomas. However, some studies indicate that patients with advanced-stage MOC might have a worse prognosis than those with advanced-stage serous ovarian carcinoma (SOC). We carried out a systematic review and meta-analysis of the current literature.
MATERIALS AND METHODS
A comprehensive literature search was carried out identifying 19 articles that compare survival of patients with MOC and patients with SOC. Meta-analyses were performed for risk ratio (RR) and hazard ratio (HR) for all International Federation of Gynecology and Obstetrics stages together, as well as for early- and advanced-stage diseases separately.
RESULTS
Overall, patients with MOC showed a lower risk of dying within 5 years (RR, 0.67; 95% confidence interval [CI], 0.64-0.69; n = 45 333) and a longer survival (HR, 0.66; 95% CI, 0.58-0.75; HR, 0.88; 95% CI, 0.78-0.98, for univariate and multivariate analyses, respectively; n = 5540) compared with those with SOC. In contrast, in advanced-stage (International Federation of Gynecology and Obstetrics stages III and IV) disease, patients with MOC have a higher risk of dying within 5 years (RR, 1.15; 95% CI, 1.13-1.17; n = 36 113) and a shorter survival (HR, 1.82; 95% CI, 1.71-1.94; n = 19 907).
CONCLUSIONS
Patients with advanced-stage MOC have a significantly worse prognosis compared with patients with SOC, whereas in early stage, the prognosis of patients with MOC is better.
Topics: Adenocarcinoma, Mucinous; Female; Humans; Ovarian Neoplasms; Prognosis
PubMed: 28399027
DOI: 10.1097/IGC.0000000000000932 -
Clinical Gastroenterology and... Oct 2017It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression to cancer. We sought to determine the cumulative incidence of development of pancreatic cancer in persons with unresected IPMNs (particularly low-risk IPMNs).
METHODS
We performed a systematic search of the MEDLINE and Embase databases through November 30, 2016 for studies reporting the cumulative incidence of pancreatic cancer in patients with unresected IPMNs or studies that provided data in sufficient detail for us to calculate cumulative incidence values. We categorized patient series as studies on low-risk IPMNs (lesions without main pancreatic duct involvement or mural nodules) or non-low-risk IPMNs. We calculated meta-analytic cumulative incidence values for pancreatic cancer at 1, 3, 5, and 10 years of follow-up by using the inverse variance method and random-effects model.
RESULTS
Among 1514 articles screened, we identified 10 studies of low-risk IPMNs (n = 2411) and 9 studies of non-low-risk IPMNs (n = 825). In studies of low-risk IPMNs, the meta-analytic cumulative incidence values for pancreatic cancer were 0.02% at 1 year (95% confidence interval [CI], 0.0%-0.23%; I= 0.0%), 1.40% at 3 years (95% CI, 0.58%-2.48%; I = 58.5%), 3.12% at 5 years (95% CI, 1.12%-5.90%; I = 88.0%), and 7.77% at 10 years (95% CI, 4.09%-12.39%; I = 79.8%). These values were much higher in studies of non-low-risk IPMNs; cumulative incidence values for pancreatic cancer were 1.95% at 1 year (95% CI, 0.0%-5.99%; I = 84.2%), 5.69% at 3 years (95% CI, 1.10%-12.77%; I = 89.9%), 9.77% at 5 years (95% CI, 3.04%-19.27%; I = 92.0%), and 24.68% at 10 years (95% CI, 14.87%-35.90%; I = 74.3%). The pooled cumulative incidence steadily increased linearly as the follow-up duration increased.
CONCLUSIONS
In a systematic review and meta-analysis, we found that low-risk IPMNs have almost 8% chance of progressing to pancreatic cancer within 10 years, and higher-risk IPMNs have almost 25% chance of progressing to cancer in 10 years; incidence values increase linearly with time. Continued long-term surveillance is therefore vital for patients with low-risk IPMNs.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Disease Progression; Humans; Incidence; Pancreatic Neoplasms; Risk Assessment
PubMed: 28342950
DOI: 10.1016/j.cgh.2017.03.020 -
Diseases of the Colon and Rectum Dec 2016Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following neoadjuvant chemoradiotherapy and curative resection for rectal cancer has not been reached.
OBJECTIVE
The aim of the current study is to use meta-analytical techniques to assess the association between mucinous histology and response to neoadjuvant chemoradiotherapy in rectal cancer.
DATA SOURCES
A comprehensive literature search of PubMed, Embase, and The Cochrane Library was performed.
STUDY SELECTION
All studies examining the effect of mucinous histology on chemotherapeutic response in rectal cancer were included.
INTERVENTIONS
No direct interventions were performed.
MAIN OUTCOME MEASURES
Outcomes of mucinous rectal adenocarcinoma were compared with nonmucinous tumors by using random-effects methods to analyze data. Data are presented as ORs with 95% CIs. The main outcomes measured were the rates of pathological complete response, tumor and nodal downstaging, positive resection margin rate, local recurrence, and overall mortality.
RESULTS
Eight comparative series describing outcomes in 1724 patients were identified, 241 had mucinous tumors (14%). Mucinous tumors had a reduced rate of pathological complete response (OR, 0.078; 95% CI, 0.015-0.397; p = 0.002) and tumor downstaging (OR, 0.318; 95% CI, 0.185-0.547; p < 0.001) following neoadjuvant chemoradiotherapy with an increased rate of positive resection margin (OR, 5.018; 95% CI, 3.224-7.810; p < 0.001) and poorer overall survival (OR, 1.526; 95% CI, 1.060-2.198; p = 0.023) following resection. Mucin expression did not significantly affect nodal downstaging (OR, 0.706; 95% CI, 0.295-1.693; p = 0.435) or local recurrence (OR, 1.856; 95% CI, 0.933-3.693; p = 0.078). There was no across-study heterogeneity for any end point.
LIMITATIONS
Most studies were retrospectively designed, and there were variations in patient populations and duration of follow-up.
CONCLUSIONS
Mucinous rectal adenocarcinoma represents a biomarker for poor response to preoperative chemoradiotherapy and is an adverse prognostic indicator.
Topics: Adenocarcinoma, Mucinous; Chemoradiotherapy; Humans; Neoadjuvant Therapy; Prognosis; Rectal Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 27824706
DOI: 10.1097/DCR.0000000000000635 -
International Journal of Gynecological... Jul 2017Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis.
Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.
Topics: Adenocarcinoma; Adenocarcinoma in Situ; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Cervix Uteri; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 27801764
DOI: 10.1097/PGP.0000000000000345 -
Pancreas Oct 2016This study aimed to evaluate the accuracy of the risk factors proposed by Fukuoka guidelines in detecting malignancy of branch-duct intraductal papillary mucinous... (Meta-Analysis)
Meta-Analysis Review
Risk Factors for Malignancy of Branch-Duct Intraductal Papillary Mucinous Neoplasms: A Critical Evaluation of the Fukuoka Guidelines With a Systematic Review and Meta-analysis.
OBJECTIVES
This study aimed to evaluate the accuracy of the risk factors proposed by Fukuoka guidelines in detecting malignancy of branch-duct intraductal papillary mucinous neoplasms.
METHOD
Diagnostic meta-analysis of cohort studies. A systematic literature search was conducted using MEDLINE, the Cochrane Library, Scopus, and the ISI-Web of Science databases to identify all studies published up to 2014.
RESULTS
Twenty-five studies (2025 patients) were suitable for the meta-analysis. The "high risk stigmata" showed the highest pooled diagnostic odds ratio (jaundice, 6.3; positive citology, 5.5; mural nodules, 4.8) together with 2 "worrisome features" (thickened/enhancing walls, 4.2; duct dilatation, 4.0) and 1 "other parameters" (carbohydrate antigen 19-9 serum levels, 4.6).
CONCLUSIONS
An "ideal risk factor" capable of recognizing all malignant branch-duct intraductal papillary mucinous neoplasms was not identified and some "dismal areas" remain. However, "high risk stigmata" were strongly related to malignancy, mainly enhancing mural nodules. Among the "worrisome features," duct dilatation and thickened/enhancing walls were underestimated, and their diagnostic performance was similar to those of "high risk stigmata." The carbohydrate antigen 19-9 serum level should be added to the Fukuoka algorithm because this value could help in carrying out correct management.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms; Risk Factors
PubMed: 27776043
DOI: 10.1097/MPA.0000000000000642 -
Archives of Gynecology and Obstetrics Nov 2016The benefit of performing an appendectomy during the surgical treatment of a mucinous borderline ovarian tumor (mBOT) is still controversial, even though clinical... (Review)
Review
OBJECTIVE
The benefit of performing an appendectomy during the surgical treatment of a mucinous borderline ovarian tumor (mBOT) is still controversial, even though clinical guidelines recommend this procedure.
PURPOSE
Our aim was to systematically assess the available evidence on appendectomy in the case of diagnosis of mBOT.
METHODS
A comprehensive search of the literature was conducted using electronic databases using the search terms: (borderline OR low malignant potential) AND (appendectomy OR appendix).
RESULTS
A total of 12 articles were retained after systematic review, including a total of 667 patients with borderline ovarian tumor. Appendectomy was performed in 232 of the patients presenting with a mBOT. Two (0.86 %) appendiceal carcinomas were confirmed on pathological examination. Both appendices were grossly abnormal at the time of surgery.
CONCLUSION
Our systematic review demonstrates that available evidence regarding the role of appendectomy in mBOT is fragmented and weak. Nevertheless, this review provides adequate evidence to highlight that appendiceal involvement in mBOTs appears to be extremely rare and microscopic appendiceal involvement is highly unlikely in apparently normal appendices. In spite of the diversity of the included studies, the lack of appendiceal involvement in all cases with apparently normal appendix is strikingly common. We can conclude that in the case of normal appearance of the appendix at the time of primary surgery, appendectomy is not mandatory. Furthermore, a patient with a normal appendiceal appearance during primary surgery with post-operative diagnosis of mBOT addition of a second look intervention seems unnecessary and even hazardous.
Topics: Adenocarcinoma, Mucinous; Appendectomy; Appendiceal Neoplasms; Female; Humans; Ovarian Neoplasms
PubMed: 27535756
DOI: 10.1007/s00404-016-4174-y -
Pancreatology : Official Journal of the... 2016The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.
METHODS
A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.
RESULTS
MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.
CONCLUSIONS
Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.
Topics: Humans; Neoplasms, Cystic, Mucinous, and Serous; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 27681503
DOI: 10.1016/j.pan.2016.09.011 -
Urologic Oncology Jan 2017To examine patient and clinicopathological features of malignant urachal neoplasms (MUN) in a population-based cohort, to investigate survival outcomes, and to review... (Review)
Review
OBJECTIVES
To examine patient and clinicopathological features of malignant urachal neoplasms (MUN) in a population-based cohort, to investigate survival outcomes, and to review the current evidence that exists in the literature.
MATERIAL AND METHODS
The Surveillance, Epidemiology, and End Results database was used to identify microscopically confirmed MUN cases diagnosed between 1988 and 2012. Kaplan-Meier analysis was used to determine median and 5-year overall survival (OS) as well as cancer-specific survival (CSS) rates. Cox proportional hazards model was employed to identify variables independently associated with cancer-specific mortality. A systematic literature review was conducted in line with the PRISMA statement.
RESULTS
A total of 420 patients with MUNs were identified. The majority were white (77.6%) and male patients (59%) who presented with low-grade (62.1%), mucinous, noncystic adenocarcinomas (42.9%). From the cohort, 19%, 15.2%, 29.5%, and 30.5% of the patients presented with American Joint Committee on Cancer Stage I to IV disease, respectively. Cancer-directed surgery was performed in 86.5% of the patients. The most common procedure performed was partial cystectomy (52.4%) followed by local tumor excision (20.7%). Median OS was 57 months (95% CI: 41.6-72.4), and median CSS was 105 months (95% CI: 61.5-148.5). Five-year OS and CSS rates were 51% and 57%, respectively. Grade and stage were independently associated with cancer-specific mortality. Mortality rates did not differ between patients who underwent partial cystectomy and radical cystectomy/exenteration (P = 0.165), even after controlling for tumor stage. A total of 16 studies reporting on 585 patients were systematically reviewed, and relevant outcomes were summarized in the Supplemental material.
CONCLUSIONS
MUNs are usually low-grade, mucinous, noncystic adenocarcinomas diagnosed at advanced stages. Overall, the prognosis is poor, and high-grade and disease stage are independently associated with cancer-specific mortality.
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Cystectomy; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Proportional Hazards Models; Radiotherapy; SEER Program; Survival Rate; United States; Urinary Bladder Neoplasms; Young Adult
PubMed: 27592530
DOI: 10.1016/j.urolonc.2016.07.021 -
BJOG : An International Journal of... Feb 2017The proportion of women with mucinous ovarian carcinoma in whom nodal metastases are identified during staging remains unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The proportion of women with mucinous ovarian carcinoma in whom nodal metastases are identified during staging remains unclear.
OBJECTIVES
To review the literature on surgical lymph node assessment during staging of women diagnosed with mucinous ovarian carcinoma.
SEARCH STRATEGY
A systematic search using synonyms of 'mucinous ovarian carcinoma' and 'lymph node assessment' was conducted in PubMed, Scopus, Embase and the Cochrane Library.
SELECTION CRITERIA
When they covered ten or more mucinous ovarian carcinoma cases, staging surgery and minimally one of the following outcomes: prevalence of metastases, stage shift or survival data.
DATA COLLECTION AND ANALYSIS
Studies were quality evaluated with the Cochrane risk-of-bias assessment tool for non-randomised studies of interventions. Outcomes were pooled using an inverse variance weighted random effects model.
MAIN RESULTS
Sixteen studies were included. In 278 women with mucinous ovarian cancer suspected to be stage I-II, a pooled proportion of 0.8% (95% CI <0.1-2.9%) had lymph node metastases and were upstaged. In those suspected of stage I (n = 184), this proportion was 0.7% (95% CI <0.1-3.8%). No difference (P = 0.287) was found in metastases between sampling at 0.0% (95% CI 0.0-3.3%) and complete pelvic and/or para-aortic lymph node dissection at 1.2% (95% CI <0.1-4.2%). One study directly compared the survival of patients staged with and without lymph node dissection and reported no significant difference.
CONCLUSIONS
Surgical lymph node assessment in women suspected of stage I-II mucinous ovarian carcinoma rarely identifies nodal metastases and consequently has no significant impact on staging.
TWEETABLE ABSTRACT
Surgical lymph node assessment in women with stage I-II mucinous ovarian cancer rarely has staging consequences.
Topics: Adenocarcinoma, Mucinous; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Ovarian Neoplasms; Survival Rate
PubMed: 27444115
DOI: 10.1111/1471-0528.14226