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Pathology International Sep 2020Cholangiocarcinoma is a malignant neoplasm originating from the biliary epithelium. Its incidence is highest in Southeast Asia, especially in Thailand. Mucinous...
Cholangiocarcinoma is a malignant neoplasm originating from the biliary epithelium. Its incidence is highest in Southeast Asia, especially in Thailand. Mucinous intrahepatic cholangiocarcinoma (mucinous iCCA), characterized by an abundant extracellular mucin pool accounting for at least 50% of total tumor volume, is an extremely rare variant of such malignancy and is notorious for rapid progression and dismal prognosis. We conducted an 11-year retrospective analysis of resected mucinous iCCAs from our institution with a systematic review on mucinous iCCAs and combined hepatocellular-mucinous cholangiocarcinoma (cHCC-mCCA). There were four resected mucinous iCCA specimens at our institution (prevalence = 0.5%). Most of the patients were male. The clinicopathological characteristics were variable. The diagnosis of mucinous iCCAs could not be rendered without pathological evaluation. Either intraductal papillary neoplasm or biliary intraepithelial neoplasia was present in three out of four cases. One patient passed away at 11 months following liver resection. A total of 19 mucinous iCCAs and four cHCC-mCCAs from previously published literature were analyzed. The 1-year mortality rate of mucinous iCCAs from our series and published literature is 35%. The present study confirmed that mucinous iCCA is an exceedingly uncommon variant of iCCA. The differential diagnoses include metastatic carcinoma with mucinous component and cHCC-mCCA.
Topics: Adenocarcinoma, Mucinous; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Incidence; Liver Neoplasms; Male; Middle Aged; Mortality; Mucin-1; Mucins; Prognosis; Retrospective Studies
PubMed: 32638458
DOI: 10.1111/pin.12983 -
Gut Jan 2021Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in... (Comparative Study)
Comparative Study
OBJECTIVE
Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC).
DESIGN
PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project).
RESULTS
Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%-2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a / wild-type molecular background (p<0.01), with more common genes mutations. Data on survival are still unclear.
CONCLUSION
PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.
Topics: Carcinoma, Pancreatic Ductal; Databases, Factual; Humans; Microsatellite Instability; Pancreatic Neoplasms
PubMed: 32350089
DOI: 10.1136/gutjnl-2020-320726 -
Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions.Hepatobiliary & Pancreatic Diseases... Jun 2020Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered...
BACKGROUND
Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered an epigenetic disease. DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor. In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma (PDAC), the epigenetic changes play a significant role.
DATA SOURCES
Relevant studies for this review were derived via an extensive literature search in PubMed via using various keywords such as pancreatic ductal adenocarcinoma, precancerous lesions, methylation profile, epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest. The literature search was intensively done considering a time frame of 20 years (1998-2018).
RESULT
In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions (pancreatic intra-epithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and chronic pancreatitis) and PDAC along with the potential biomarkers. We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC. A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC (ppENK, APC, p14/5/16/17, hMLH1 and MGMT) are also documented. We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy. Epigenetic inactivation occurs by hypermethylation of CpG islands in the promoter regions of tumor suppressor genes. We listed all hyper- and hypomethylation of CpG islands of several genes in PDAC including its precancerous lesions.
CONCLUSIONS
The concept of the review would help to understand their biological effects, and to determine whether they may be successfully combined with other epigenetic drugs. However, we need to continue our research to develop more specific DNA-demethylating agents, which are the targets for hypermethylated CpG methylation sites.
Topics: Biomarkers, Tumor; Carcinogenesis; Carcinoma in Situ; Carcinoma, Pancreatic Ductal; DNA Methylation; Epigenesis, Genetic; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Pancreatitis, Chronic; Precancerous Conditions
PubMed: 32312637
DOI: 10.1016/j.hbpd.2020.03.010 -
Scandinavian Journal of Surgery : SJS :... Mar 2020Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary...
BACKGROUND AND AIMS
Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up.
MATERIALS AND METHODS
Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms.
RESULTS
The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases.
CONCLUSION
Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.
Topics: Aftercare; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Practice Guidelines as Topic; Precancerous Conditions
PubMed: 32009571
DOI: 10.1177/1457496919900414 -
Revista Espanola de Enfermedades... Feb 2020Perforation in colorectal cancer is an uncommon condition, and neoplastic invasion of the abdominal wall with local infection is even rarer. Our objective is to present...
Perforation in colorectal cancer is an uncommon condition, and neoplastic invasion of the abdominal wall with local infection is even rarer. Our objective is to present the case of an 84-year-old male with right colon cancer that manifested as an inguinal abscess, and also to perform a systematic review of the literature in PubMed, EMBASE, and Web of Science. A total of 59 cases in retrospective studies were found. Median age was 64 years, thirty cases were men and twenty-nine were women (51% and 49%, respectively). The most common location was the right colon with 27 cases (46%), followed by the left colon with 18 cases (31%), 12 cases in the transverse colon (20%), and 2 cases with colonic synchronous neoplasm (3%). Surgery was performed in two or more occasions for 33 cases (60%), and on one occasion for 21 cases (38%); medical treatment alone was administered in one case (2%). The most common histological type was adenocarcinoma (64%), followed by its mucinous variant (22%). There was recurrence in 33% of cases. Mortality at follow-up was 47%. As a limitation of our study, follow-up was heterogeneous, making it impossible to interpret long-term results regarding the influence of treatment on patient survival, also difficulted by the urgent nature of the condition and its exceptional incidence. Further studies are needed with prospective data collection on the management of colorectal cancer in the emergency setting, standardizing follow-up in order to facilitate an adequate analysis of the prognosis of the disease.
Topics: Abscess; Aged, 80 and over; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Retrospective Studies
PubMed: 31985253
DOI: 10.17235/reed.2020.5887/2018 -
Annals of Translational Medicine Nov 2019Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor with a disease spectrum ranging from low-grade dysplasia to invasive carcinoma. The... (Review)
Review
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a cystic tumor with a disease spectrum ranging from low-grade dysplasia to invasive carcinoma. The evidence for adjuvant treatment in invasive IPMN is limited and mostly derived from studies in conventional pancreatic ductal adenocarcinoma (PDAC). We performed a systematic review focusing on all clinical studies concerning the efficacy of adjuvant therapy in patients with invasive IPMN. We identified 8 retrospective cohort studies, using either adjuvant chemotherapy alone (n=1), adjuvant radiotherapy alone (n=1) or adjuvant chemotherapy in combination with radiation (n=6). Adjuvant therapy was associated with a survival benefit in 7 out of the 8 studies. Specific survival benefit was noted for patients with node-positive disease, higher TNM stage, positive resection margins, poor differentiation and tubular subtype. We conclude that adjuvant therapy may be beneficial in invasive IPMN, but current data suggest that it should be given selectively based on individual tumor characteristics. Further prospective, randomized studies are warranted.
PubMed: 31930090
DOI: 10.21037/atm.2019.10.37 -
Romanian Journal of Morphology and... 2019Primary ovarian hydatid disease (HD) is a rare entity, produced by the larval stage of Echinococcus granulosus. HD commonly involves liver, lung, abdomen cavity, spleen...
Primary ovarian hydatid disease (HD) is a rare entity, produced by the larval stage of Echinococcus granulosus. HD commonly involves liver, lung, abdomen cavity, spleen and is unusually identified in pelvic organs. Based on our knowledge, the paper reviews 27 literature reports of ovarian HD, diagnosed during the last 20 years, providing a valuable database. Patients' ages ranged between 12-76 years, the gross appearance was that of 40-330 mm diameter hydatid cysts (HCs), 66.66% of them being primary. According to these reports, ovarian HD has non-specific clinical manifestations, such as abdominal or pelvic pain, nausea, dysmenorrhea or amenorrhea. The diagnosis may be achieved by abdominal ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI), serological exams, such as eosinophilia (in 10-30% of patients) or indirect hemagglutination and immunoglobulin (IgG) antibodies detection. Ovarian HC microscopic pattern is characterized by three layers: pericyst or adventitia (host origin), germinal layer (endocyst), and laminated membrane (ectocyst). The immunoreaction triggered by parasites is initially rich in macrophages and neutrophils, followed by eosinophils and lymphocytes, with numerous cluster of differentiation 8 (CD8)-positive T-cells in active lesions and progressive forms. Concomitant ovarian diseases are relatively rare, being represented by borderline tumors (n=2 cases), mucinous cystadenoma (n=1 case), hemorrhagic cyst (n=1 case), and serous adenocarcinoma (n=1 case). In conclusion, the ovarian location of HD should be considered in any differential diagnosis of a cystic lesion, while it does not exclude synchronous ovarian tumors. These cases reinforce the necessity of better measures of prophylaxis and screening of HD in endemic areas.
Topics: Adolescent; Adult; Aged; Child; Echinococcosis; Female; Humans; Immunohistochemistry; Middle Aged; Ovarian Cysts; Young Adult
PubMed: 31912083
DOI: No ID Found -
European Journal of Surgical Oncology :... May 2020To analyze all published studies comparing minimally invasive surgery (MIS) with laparotomic one in the surgical treatment of high-risk endometrial cancer (EC) in term... (Comparative Study)
Comparative Study
OBJECTIVE
To analyze all published studies comparing minimally invasive surgery (MIS) with laparotomic one in the surgical treatment of high-risk endometrial cancer (EC) in term of operative, peri-operative and oncological outcomes.
DATA SOURCES
We conducted a systematic literature search in PubMed between January 1995-March 2019.
METHODS OF STUDY SELECTION
Titles and abstracts were analyzed by two reviewers. A set of explicit criteria was used for selection of literature: 1) randomized controlled trials (RCT), prospective or retrospective cohort studies, given the rarity of this tumor and the concomitant lack of data in the form of large trials, all reviewed original report publications with an appropriate number of subjects were considered and included; 2) participants of interest being patients who have suffered from high risk EC 3) the outcome measures including overall survival (OS), disease-free survival (DFS) and recurrence, (4) English language, (5) abstract available.
RESULTS
Thirty relevant articles were selected for full reading. For final analysis 20 studies were selected. Then, as second step, the full articles were evaluated to determine whether full inclusion criteria were met. In total, 9 papers were identified and included.
CONCLUSION
MIS appears to be safe in the management of high-risk EC patients, showing better perioperative and postoperative outcomes and comparable oncological outcomes than open surgery. Prospective randomized trial would be needed to confirm this data.
Topics: Adenocarcinoma, Clear Cell; Carcinoma, Endometrioid; Carcinosarcoma; Endometrial Neoplasms; Female; Humans; Hysterectomy; Laparoscopy; Laparotomy; Minimally Invasive Surgical Procedures; Neoplasm Grading; Neoplasms, Cystic, Mucinous, and Serous; Risk
PubMed: 31818527
DOI: 10.1016/j.ejso.2019.11.519 -
Annals of Surgical Oncology Jan 2020The role of somatic mutation profiling in the management of appendiceal mucinous tumors (AMTs) is evolving. Using a systematic review, we identified somatic alterations...
INTRODUCTION
The role of somatic mutation profiling in the management of appendiceal mucinous tumors (AMTs) is evolving. Using a systematic review, we identified somatic alterations (SAs) that comprise histopathologic types of AMTs and those associated with aggressive clinical phenotypes.
METHODS
MEDLINE/PubMed was searched for studies on AMTs including molecular markers or genomic alterations, published between 1990 and 2018. Studies were grouped under low- and high-grade histological type for primary and metastatic tumors.
RESULTS
Twenty-one studies involving 1099 tumors (primary/metastatic) were identified. Seven studies involving 101 primary low-grade AMTs identified KRAS (76.5%) as the predominant SA. Four studies noted GNAS in 45.2% of 42 low-grade appendiceal mucinous neoplasms, and KRAS was identified in 74.4% of 14 studies with 238 low-grade pseudomyxoma peritonei (PMP). GNAS was noted in 56% of 101 tumors and TP53 was noted in only 9.7% of 31 tumors. Primary high-grade tumors demonstrated lower SAs in KRAS (50.4% of 369 tumors) and GNAS (27.8% of 97 tumors), and higher SAs in TP53 (26.0% of 123 tumors). In high-grade PMP, SAs were noted in KRAS (55.0% of 200 tumors), GNAS (35.0% of 60 tumors), and TP53 (26.3% of 19 tumors). No clear association was noted between SAs and survival.
CONCLUSIONS
KRAS and GNAS are frequently altered in low-grade AMTs, while TP53 is frequently altered in high-grade AMTs, with no apparent change in expression between primary and metastatic tumors. Although SAs may provide valuable insights into variability in tumor biology, larger studies utilizing clinically annotated genomic databases from multi-institutional consortiums are needed to improve their identification and clinical applicability.
Topics: Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Biomarkers, Tumor; Genetic Markers; Humans; Mutation; Phenotype; Prognosis
PubMed: 31583543
DOI: 10.1245/s10434-019-07879-7 -
The American Journal of Surgical... Feb 2020Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the... (Meta-Analysis)
Meta-Analysis
Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the formation of extracellular mucin pools can be identified in the resection specimen after neoadjuvant CRT. The association of mucin pool formation with clinicopathologic variables and outcomes is unclear. The aim of this study was to meta-analyze all available evidence with regard to mucin pool formation and clinicopathologic outcomes following neoadjuvant CRT for rectal cancer. A comprehensive search for published studies analyzing outcomes between patients who formed mucin pools and patients who did not following neoadjuvant CRT for rectal cancer was performed. A random-effects model was used to combine the data. This study adhered to the recommendations of the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. Data from 11 studies describing 1947 patients were included. Mucin pool formation was not associated with sex, T stage, N stage, tumor regression, pathologic complete response rate, lymphovascular invasion, perineural invasion, differentiation, margin status, local or distant recurrence, and disease-free or overall survival. Mucin pool formation is not associated with tumor response or downstaging; furthermore, on the basis of these data, it is not associated with local or systemic recurrence rate or survival.
Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Chemoradiotherapy, Adjuvant; Humans; Models, Statistical; Mucins; Neoadjuvant Therapy; Neoplasm Staging; Rectal Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 31567193
DOI: 10.1097/PAS.0000000000001373