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Discover Oncology Feb 2021Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare... (Review)
Review
Clinicopathological factors and survival outcomes of signet-ring cell and mucinous carcinoma versus adenocarcinoma of the colon and rectum: a systematic review and meta-analysis.
BACKGROUND
Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare clinicopathological characteristics, recurrence and overall survival between colorectal signet-ring cell (SC) and mucinous carcinoma (MC) to conventional adenocarcinoma (AC).
METHODS
A literature search of MEDLINE, EMBASE, Ovid and Cochrane Library was performed for studies that reported data on clinicopathological and survival outcomes on SC and/or MC versus AC from January 1985 to May 2020. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed.
RESULTS
Thirty studies of 1,087,055 patients were included: 11,510 (1.06%) with SC, 110,179 (10.13%) with MC and 965,366 (88.81%) with AC. Patients with SC were younger than patients with AC (WMD - 0.47; 95% CI - 0.84 to -0.10; I 88.6%; p = 0.014) and more likely to have right-sided disease (OR 2.12; 95% CI 1.72-2.60; I 82.9%; p < 0.001). Locoregional recurrence at 5 years was more frequent in patients with SC (OR 2.81; 95% CI 1.40-5.65; I 0.0%; p = 0.004) and MC (OR 1.92; 95% CI 1.18-3.15; I 74.0%; p = 0.009). 5-year overall survival was significantly reduced when comparing SC and MC to AC (HR 2.54; 95% CI 1.98-3.27; I 99.1%; p < 0.001 and HR 1.38; 95% CI 1.19-1.61; I 98.6%; p < 0.001, respectively).
CONCLUSION
SC and MC are associated with right-sided lesions, advanced stage at presentation, higher rates of recurrence and poorer overall survival. This has strong implications towards surgical and oncological management and surveillance of colorectal cancer.
PubMed: 35201441
DOI: 10.1007/s12672-021-00398-6 -
European Journal of Surgical Oncology :... Jul 2022Conflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conflicting evidence exists regarding the role of adjuvant therapy for Invasive Intraductal Papillary Mucinous Neoplasms (i-IPMN). This meta-analysis assessed whether adjuvant therapy improves Overall Survival (OS) in patients with resected i-IPMN.
METHODS
A systematic review and meta-analysis was performed. The primary endpoint was the effect of adjuvant therapy on OS. Secondary endpoint evaluated adjuvant therapy with regard to nodal disease, positive resection margins, tumour grade and differentiation. A meta-analysis of pooled hazard ratios (HRs) with an inverse variance and a random-effects model was performed. Risk of bias was determined with the GRADE approach and MINORS criteria.
RESULTS
Ten articles with a total of 3252 patients were included. No statistically significant difference in the OS was noted with adjuvant therapy for i-IPMN in the entire cohort (HR = 1; 95% CI = 0.75-1.35; P = 0.98). However, a survival benefit was noted in a subgroup of patients with an aggressive disease phenotype; nodal involvement (HR = 0.56; 95% CI = 0.39-0.79; P = 0.001) and advanced staged tumours (≥stage 2, HR = 1.42; 95% CI = 1.11-1.82; P = 0.005) CONCLUSIONS: The concurrent evidence base for adjuvant therapy for i-IPMN is limited. After acknowledging the limitations of the data, the current literature suggests that adjuvant therapy should be reserved for patients with resected i-IPMN that have adverse tumour biology.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Humans; Neoplasm Invasiveness; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 35144836
DOI: 10.1016/j.ejso.2022.01.028 -
European Journal of Surgical Oncology :... Mar 2022It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies.
AIMS
We performed a pooled estimate of the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia, with a particular focus on the comparison to the general population.
METHODS
Computerized bibliographic search of main databases was performed through February 2021. The primary endpoint was the pooled incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms. Additional outcome was the comparison between intraductal papillary mucinous neoplasia patients and the general population, expressed in terms of standardized incidence ratio along with 95% confidence intervals.
RESULTS
Eighteen studies with 8709 patients were included. The pooled rate of metachronous extrapancreatic malignancies was 10 (6-13)/1000 persons-year. No difference was observed according to intraductal papillary mucinous neoplasia histology and sex, whereas a significantly superior incidence of extrapancreatic malignancies was observed in patients with main-duct (36.7%, 25.4%-48%) as compared to branch-duct intraductal papillary mucinous neoplasia (26.2%, 17.6%-34.8%; p = 0.03). Pooled standardized incidence ratio comparing expected rates in the general population was 1.01 (0.79-1.29); no difference was observed concerning rates of metachronous gastric cancer (standardized incidence ratio 1.60, 0.72-3.54) and colorectal cancer (1.29, 0.92-1.18), whereas biliary cancer was observed more frequently in intraductal papillary mucinous neoplasia patients (2.29, 1.07-4.93).
CONCLUSION
Patients with intraductal papillary mucinous neoplasia harbor an overall rate of extrapancreatic malignancies as high as 27.3%. The rate of metachronous extrapancreatic malignancies is not superior to the general population.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34620511
DOI: 10.1016/j.ejso.2021.09.018 -
Annals of Surgical Oncology Feb 2022The consensus guidelines for branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas are mostly based on imaging features. This study aimed to... (Meta-Analysis)
Meta-Analysis Review
Imaging Features for Predicting High-Grade Dysplasia or Malignancy in Branch Duct Type Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Systematic Review and Meta-Analysis.
BACKGROUND
The consensus guidelines for branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas are mostly based on imaging features. This study aimed to determine imaging features and their diagnostic accuracy for predicting high-grade dysplasia (HGD)/malignancy in BD-IPMN, including mixed type.
METHODS
The PubMed, Embase, and Cochrane databases were searched, and data were extracted from relevant studies. As the main diagnostic accuracy index, diagnostic odds ratios (DORs) of imaging features for diagnosing HGD/malignancy in BD-IPMNs were pooled using the random-effects model. A bivariate random-effects approach was used to construct summary receiver operating characteristic curves for sensitivity and specificity estimation.
RESULTS
The pooled DOR was the highest for the enhanced solid component/mural nodule (MN) (DOR, 12.21; 95 % confidence interval [CI], 6.14-24.27), followed by a main pancreatic duct (MPD) diameter of 10 mm or greater (DOR, 7.93; 95 % CI, 3.02-20.83), solid component (DOR, 4.85; 95 % CI, 2.49-9.42), lymphadenopathy (DOR, 4.84; 95 % CI, 1.11-21.06), MN (DOR, 4.48; 95 % CI, 3.15-6.39), an MPD diameter of 5 mm or greater (DOR, 3.69; 95 % CI, 2.62-5.19), abrupt change in MPD caliber with distal pancreatic atrophy (DOR, 2.65; 95 % CI, 1.66-4.24), thickened/enhancing walls (DOR, 2.38; 95 % CI, 1.57-3.60), and cyst size of 3 cm or larger (DOR, 1.98; 95 % CI, 1.48-2.64). The largest area under the curve (0.89 and 0.95, respectively) and high specificity (0.95 and 0.98, respectively) also were found for enhanced solid component/MN and an MPD diameter of 10 mm or greater, albeit with low sensitivity (0.38 and 0.14, respectively).
CONCLUSIONS
The aforementioned imaging features could aid in predicting HGD/malignancy of BD-IPMN. Furthermore, enhanced solid component/MN and an MPD diameter of 10 mm or greater were the most important predictors of HGD/malignancy in BD-IPMN and should be considered as indications for surgery.
Topics: Adenocarcinoma, Mucinous; Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Ducts; Pancreatic Neoplasms; Retrospective Studies
PubMed: 34554343
DOI: 10.1245/s10434-021-10662-2 -
Modern Pathology : An Official Journal... Jan 2022The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms... (Comparative Study)
Comparative Study
Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis.
The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms
PubMed: 34518632
DOI: 10.1038/s41379-021-00902-x -
Annals of Gastroenterology 2021The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF),...
BACKGROUND
The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF), whereas the American College of Gastroenterology recommends EUS for ≥1 HRF. This systematic review and meta-analysis compared the diagnostic accuracy of using ≥1 vs. ≥2 HRF for assessing the risk of advanced neoplasia (AN) and performing EUS in PCL.
METHODS
An electronic database search was performed for eligible studies. AN was defined as pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm or mucinous cystadenoma with high-grade dysplasia, pancreatic intraepithelial neoplasia and pancreatic neuroendocrine tumors. HRF included cyst size ≥3 cm, solid component, and dilated pancreatic duct ≥5 mm. The primary outcome was the sensitivity and specificity of using ≥1 vs. ≥2 HRF as an indication for EUS to detect AN in PCL.
RESULTS
Of 38 studies initially screened, 8 were included in the final analysis. Seven studies assessed the accuracy of ≥2 HRF and 4 studies assessed ≥1 HRF. The pooled sensitivity, specificity, positive and negative predictive values of EUS for detecting AN were 41.7% (95% confidence interval 19.5-67.8%), 90.8% (81.9-95.5%), 30.4% (19.4-44.2%) and 94.3% (89.6-97.0%) with ≥2HRFs, and 77.1% (66.1-85.3%), 72.7% (50.4-87.5%), 17.95% (10.3-29.4%), 98.1% (90.8-99.6%), respectively, with ≥1 HRF.
CONCLUSION
Performing EUS for PCL with ≥1 HRF could offer greater sensitivity in detecting AN compared to ≥2 HRF, with a similar negative predictive value.
PubMed: 34475747
DOI: 10.20524/aog.2021.0630 -
Colorectal Disease : the Official... Nov 2021Proactive detection and treatment strategies have achieved encouraging survival outcomes for patients with early peritoneal metastases (PM), but these costly and... (Meta-Analysis)
Meta-Analysis Review
AIM
Proactive detection and treatment strategies have achieved encouraging survival outcomes for patients with early peritoneal metastases (PM), but these costly and invasive approaches can only be applied to selected high-risk patients. This meta-analysis aimed to identify the risk factors for metachronous PM after curative surgery for colorectal cancer (CRC).
METHOD
The study was registered at PROSPERO (CRD42020219187). Databases were searched for studies comparing clinical and histopathological characteristics between patients with metachronous peritoneal metastases from colorectal cancer (pmCRC) and patients without (non-pmCRC).
RESULTS
Thirty-six studies were included. Metachronous PM were positively associated with perforation (OR 1.920; 95% CI 1.144-3.223; P = 0.014), poor differentiation (OR 2.291; 1.603-3.275; P < 0.001), T4 (OR 2.897; 1.248-6.726; P = 0.013), N1-2 (OR 3.429; 2.684-4.381; P < 0.001), mucinous adenocarcinoma (OR 4.175; 1.798-9.692; P = 0.001), obstruction (OR 4.467; 1.919-10.398; P = 0.001), synchronous ovarian metastases (OR 5.005; 1.140-21.977; P = 0.033), positive peritoneal carcinoembryonic antigen mRNA (OR 9.472; 3.643-24.631; P < 0.001), elevated serum carcinoembryonic antigen (preoperative group, OR 3.545, 1.486-8.459, P = 0.004; postoperative group, OR 13.673, 2.222-84.129, P = 0.005), elevated serum cancer antigen 19-9 (preoperative group, OR 5.281, 2.146-12.994, P < 0.001; postoperative group, OR 18.646, 6.429-54.083, P < 0.001) and positive peritoneal cytology (OR 25.884; 11.372-58.913; P < 0.001).
CONCLUSION
These evidence-based risk factors are conducive to designing early detection and proactive treatment strategies, enabling precision medicine.
Topics: Adenocarcinoma, Mucinous; Colorectal Neoplasms; Humans; Peritoneal Neoplasms; Peritoneum; Prognosis; Risk Factors
PubMed: 34411399
DOI: 10.1111/codi.15880 -
BJS Open Jul 2021Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but...
BACKGROUND
Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but no universally accepted histological grading has been established. The aim of this systematic review was to provide historical insight to understand current grading classifications, basic histopathological features of each category, and to define which classification correlates best with prognosis.
METHODS
MEDLINE and the Cochrane Library were searched for studies that reported survival across different pathological grades in patients with mucinous neoplasm of the appendix with PD treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PRISMA guidelines were followed.
RESULTS
Thirty-eight studies were included. Ronnett's classification was the most common (9 studies). Classifications proposed by the Peritoneal Surface Oncology Group International (PSOGI) (6 studies) and the seventh or eighth edition of the AJCC (7 studies) are gaining in popularity. Nine studies supported a two-tier, 12 a three-tier, and two a four-tier classification system. Three studies demonstrated that acellular mucin had a better prognosis than low-grade pseudomyxoma peritonei in the PSOGI classification or M1bG1 in the eighth edition of the AJCC classification. Four studies demonstrated that the presence of signet ring cells was associated with a worse outcome than high-grade pseudomyxoma peritonei in the PSOGI classification and M1bG2 in the eighth edition of the AJCC.
CONCLUSION
There is a great need for a common language in describing mucinous neoplasms of the appendix with PD. Evolution in terminology as a result of pathological insight turns the four-tiered PSOGI classification system into a coherent classification option.
Topics: Appendiceal Neoplasms; Appendix; Cytoreduction Surgical Procedures; Humans; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 34355239
DOI: 10.1093/bjsopen/zrab059 -
Journal of Cancer Research and Clinical... Jun 2022Abscess or fistula of the anal region is an uncommon presentation of malignancy. Under the assumption of a benign condition, diagnostics is often delayed, resulting in...
Non-mucinous adenocarcinomas and squamous cell carcinomas of the anal region masquerading as abscess or fistula: a retrospective analysis and systematic review of literature.
PURPOSE
Abscess or fistula of the anal region is an uncommon presentation of malignancy. Under the assumption of a benign condition, diagnostics is often delayed, resulting in advanced tumour stages at first diagnosis. Due to the case rarity, treatment guidelines for cancers of anorectal region masquerading as abscess or fistula are missing.
METHODS
We analysed all patients presenting with an abscess or fistula of the anal region in our department between January 2004 and August 2020. The malignancies were included to our study to acquire data on clinical presentation, treatment and outcome. Furthermore, a systematic review to present adenocarcinomas and squamous cell carcinomas associated to an abscess or fistula was performed.
RESULTS
0.5% of the patients treated for an abscess or fistula of the anal region met the selection criteria. Mean time from the onset of symptoms to diagnosis of malignancy was 100 days. Histology revealed adenocarcinoma and squamous cell carcinoma each in two patients. All patients had locally advanced tumours without distant metastases, in two cases with regional lymph-node metastases. Neoadjuvant chemoradiation was applied in two patients. All patients underwent abdomino-perineal resection of the rectum. The overall outcome reveals a recurrence-free survival of 4.5 and 3 years for two patients. Further two patients died within 5 months after the primary resection.
CONCLUSION
Advanced carcinomas of the anorectal region may masquerade as abscess or fistula, cause diagnostic problems and delay oncologic treatment. However, even in these very advanced situations, surgical therapy with curative intent should be attempted.
Topics: Abscess; Adenocarcinoma; Carcinoma, Squamous Cell; Fistula; Humans; Rectum; Retrospective Studies
PubMed: 34338860
DOI: 10.1007/s00432-021-03747-8 -
Cancers Jun 2021Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be... (Review)
Review
Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy. In this systematic review, we assessed the potential predictive role of high-TMB in pancreatic ductal adenocarcinoma (PDAC), as well as the histo-molecular features of high-TMB PDAC. High-TMB appeared as a rare but not-negligible molecular feature in PDAC, being present in about 1.1% of cases. This genetic condition was closely associated with mucinous/colloid and medullary histology ( < 0.01). PDAC with high-TMB frequently harbored other actionable alterations, with microsatellite instability/defective mismatch repair as the most common. Immunotherapy has shown promising results in high-TMB PDAC, but the sample size of high-TMB PDAC treated so far is quite small. This study highlights interesting peculiarities of PDAC harboring high-TMB and may represent a reliable starting point for the assessment of TMB in the clinical management of patients affected by pancreatic cancer.
PubMed: 34206554
DOI: 10.3390/cancers13133119