Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk.

BACKGROUND AND AIMS: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs. METHODS: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs. RESULTS: A total of 457 HRIs were followed for 48 (range 2-172) months; the estimated cumulative IPMN incidence was 46% (95% confidence interval, 28%-64%). In comparison with 442 control individuals, IPMNs in HRIs were more likely to grow ≥2.5 mm/y (31% vs 7%; P < .001) and develop worrisome features (32% vs 19%; P = .010). PV carriers with IPMNs more often displayed neoplastic progression (n = 3 [11%] vs n = 6 [1%]; P = .011), while familial pancreatic cancer kindreds did not (n = 0 [0%]; P = 1.000). The malignancy risk in a PV carrier with an IPMN was 23% for growth rates ≥2.5 mm/y (n = 13), 30% for ≥5 mm/y (n = 10), and 60% for ≥10 mm/y (n = 5). CONCLUSIONS: The cumulative incidence of IPMNs in HRIs is higher than previously reported in the general population. Compared with sporadic IPMNs, they have an increased growth rate. PV carriers with IPMNs are suggested to be at a higher malignancy risk. Intensive follow-up should be considered for PV carriers with an IPMN growing ≥2.5 mm/y, and surgical resection for those growing ≥5 mm/y.

Metabolic Syndrome Accelerates the Age-Related Increase of Intraductal Papillary Mucinous Neoplasm of the Pancreas.

OBJECTIVES: Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear. METHODS: A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age. RESULTS: Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28-3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14-6.72; P = 0.003). CONCLUSIONS: The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.

Factors that contribute to the recurrence of mucinous ovarian cancer: Monocenter retrospective evaluation.

Purpose: In this study, we aimed to put forth the factors that contribute to the recurrence of mucinous ovarian cancer. Materials and Methods: Forty-four mucinous ovarian cancer patients who have presented to our clinic between February 2006 and May 2018 took part in the study. In order to predict the factors that contribute to recurrence, the univariate and the multivariate logistic regressions were utilized. The Kaplan-Meier survival analysis was utilized for survival and the log-rank test was used for the discrepancies between the groups. In the analysis of the data, the Statistical Package for the Social Sciences 22 program was used. It was acknowledged to have statistical meaning when the P value in all the tests was lower than 0.05. Findings: Recurrence was detected in 20 out of 44 patients who participated in the study. The ages of the patients who did not experience recurrence were significantly lower ( P = 0.001). The patients were detected mostly in Stage 1 (36.4%). In the group of patients without recurrence, systemic lymphadenectomy (43.2%) was greater ( P = 0.019). Lymph node metastasis was three times higher in the group that experienced recurrence ( P = 0.047). When the two groups were compared, the platinum resistance was considerably greater in the group with recurrence ( P = 0.005). In terms of residual tumor, the rate of complete resection was (9%) better in the group that experienced recurrence compared to the group that did not experience recurrence, with a rate of 45.5%. While 12 patients who experienced recurrence died, 6 people died in the other group. From the factors that contribute to recurrence, in terms of residual tumor quantity, this was grouped as complete (R0) resection and optimal + suboptimal (R1 + R2) resection and the following were determined: odds ratio (OR) - 5.7 (95% confidence interval [CI]: 1.56-20.9) and P = 0.008 for R1 + R2. In univariate analysis, the OR was determined as 1.16 (95% CI: 1.06-1.27) for age. Possessing a Stage 2 and higher disease statistically contributed considerably to the recurrence compared to Stage 1 disease (OR: 6.33; 95% CI: 1.59-25.22; P = 0.009). Age was determined as an independent prognostic risk factor in the multivariate analysis (OR: 1.10 [95% CI: 1.04-1.25]), P = 0.018. Furthermore, the OR for the advanced-stage (Stage 2 or higher) patients in the multivariate analysis was determined as 7.88 (95% CI: 0.78-78.8) and was found to be statistically significant at limits ( P = 0.079). Results: We have put forth that the genetic, biological, and clinical characteristics of mucinous ovarian cancers differ from that of other epithelial ovarian cancers, and that age, advanced stage, and residual tumor quantity are prognostic risk factors in terms of recurrence, and that age is an independent prognostic risk factor. Conclusion: Biological and clinical characteristics of mucinous ovarian cancers differ from those of other epithelial ovarian cancers, and we observed that the age, advanced stage, and the amount of residual tumor regarding recurrence are prognostic risk factors, while age was determined as an independent prognostic risk factor.

Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study.

BACKGROUND: The degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. METHODS: This is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. RESULTS: Out of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0-252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. CONCLUSION: Overall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

The Landmark Series: Intraductal Papillary Mucinous Neoplasms of the Pancreas-From Prevalence to Early Cancer Detection.

Modern series report a prevalence of pancreatic cysts in the general population of up to 50% in prospective studies. Of these, about half will be pancreatic cystic neoplasms (PCNs) that have varying degrees of malignant potential. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are the most common PCNs and are known predecessors of pancreatic adenocarcinoma. Critically, they are one of the only radiographically identifiable precursors of pancreatic cancer and thus provide an opportunity for early cancer detection and surgical resection with curative intent. The combination of high prevalence and potential for malignant degeneration underscore the relevance of discussing the best management of IPMNs and improving the existing standard of care. Landmark data on IPMN prevalence, guidelines, surveillance, biomarkers, and immune landscape are highlighted.

Low-grade mucinous neoplasms (LAMN) of the appendix in Germany between 2011 and 2018: a nationwide analysis based on data provided by the German Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI).

INTRODUCTION: Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population. METHODS: Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum für Krebsregisterdaten-ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data. RESULTS: A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07% were female and 36.93% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86% of cases (n = 152). A total of 49.34% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77% vs. 73.27%). DISCUSSION: In this study, we observed an incidence of LAMN in 0.13% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up.

Clinical significance of pancreatic calcifications: a 15-year single-center observational study.

OBJECTIVES: Pancreatic calcifications (PC) are considered specific for chronic pancreatitis (CP), but PC may also be present in non-CP diseases. The aims are to understand the pattern of calcifications in different diseases and to determine they were related to malignant diseases. METHODS: A retrospective study was performed including patients with PC or CP undergoing surgery in the Department of General Surgery of Ruijin Hospital from January 2003 to June 2018. RESULTS: PC were observed in 168 (4.5%) of the 3755 patients with pancreatic lesions treated during the study period. The majority of patients with PC had three kinds of CP (73.2%) while 26.8% had other five kinds of non-CP diseases. In patients with non-CP diseases, the incidence of PC in malignant intraductal papillary mucinous neoplasm (IPMN) was significantly higher than benign IPMN (8.3% vs. 0.7%, p = 0.004). In patients of CP with pancreatic mass (n = 81), PC (Odds ratio = 28.6, p = 0.000), advanced age (> 55 years) and parenchymal atrophy were independent predictors for malignancy. In patients of CP without pancreatic mass (n = 110), there were 82 cases (74.5%) with PC and 5 cases (4.5%) with pancreatic ductal adenocarcinoma. The regression model of risk factors was not successful. CONCLUSIONS: The disease spectrum with PC was very diverse. PC may be related to malignant IPMN in non-CP diseases and is related to malignancy in the patients of CP with pancreatic mass and indications for resection.

Epidemiological Factors Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Dual Center Case-Control Study.

OBJECTIVE: The present study aimed to identify epidemiological factors associated with the development of intraductal papillary mucinous neoplasms (IPMN) of the pancreas comparing patients after IPMN resection with population-based controls. METHODS: Preoperative data of 811 patients undergoing pancreatic resection for IPMN were matched in a 1:1 ratio with a random sample of volunteers from the Study of Health in Pomerania, which showed no pancreatic cyst greater than 2 mm in magnetic resonance cholangiopancreaticography. RESULTS: A total of 811 controls with a mean age of 61.9 years (standard deviation, 8.4 years) were matched to cases with a mean age of 66.1 years (standard deviation, 9.3 years). A previous history of pancreatitis, endocrine pancreatic insufficiency was significantly more frequent in IPMN patients compared with controls (P = 0.001). Moreover, adjusted data revealed that urogenital cancer (P = 0.034), colorectal cancer (P = 0.021), as well as first-degree family history of colorectal cancer (P = 0.001) were significantly more frequent in IPMN patients. CONCLUSIONS: A history of urogenital and colorectal cancer often coincides with IPMN, which have an indication for surgery and are associated with preoperative episodes of pancreatitis and with endocrine insufficiency. Prospective studies are needed to investigate the role of these factors in IPMN development.

Improved long-term survival of corpus cancer in Japan: A 40-year population-based analysis.

The incidence of uterine corpus cancer has been increasing globally due to increase in obesity. However, a detailed analysis of long-term epidemiological trends of corpus cancer in Japan, where obesity is relatively minimal, has not been conducted. In this retrospective, population-based study using the Osaka Cancer Registry, we analyzed 15 255 cases of corpus neoplasia registered between 1977 and 2016. We determined the age-standardized incidence, mortality, relative survival and conditional survival rates, and the treatment trends for corpus cancer over the last 40 years in Japan. The age-standardized incidence rate of corpus neoplasia increased sharply in 2000-2011 (APC = 9.9, 95% CI: 8.4-11.3), whereas the mortality rate trended to a much more modest increase (APC = 3.3, 95% CI: 2.7-3.8). Compared to 1977-2000, 10-year survival rates for post-2000 cases of localized and regional corpus cancers significantly improved (from 87.7% [95% CI: 85.8-89.4] to 94.2% [95% CI: 92.7-95.7] and from 47.5% [95% CI: 43.3-51.6] to 64.4% [95% CI: 61.0-67.6], respectively). This was largely associated with the significant increase in the percentage of localized and regional patients who received chemotherapy instead of radiation as an adjuvant therapy combined to surgery (P < .001 for both). We found that each histological type (endometrioid carcinoma, serous carcinoma, clear cell carcinoma and carcinosarcoma) has different characteristics of trend of age-standardized incidence rate, relative survival and distribution of extent of disease. In endometrioid carcinoma, the age-standardized incidence rate increased consistently after 1990, but the rate of increase was decreasing after 1997.

Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies: A systematic review with meta-analysis.

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.

Prevalence and Risk Factors for Intraductal Papillary Mucinous Neoplasm in Patients With Chronic Kidney Disease: A Single-Center Case-Control Study.

OBJECTIVES: The exact prevalence for intraductal papillary mucinous neoplasm (IPMN) in patients with chronic kidney disease (CKD) remains unknown. In this single-center case-control study, we aimed to study the prevalence and risk factors for IPMN in patients with CKD. METHODS: We performed a retrospective case-control study comparing patients with and without CKD who had magnetic resonance imaging of the abdomen performed between January 2018 and December 2018. Patient demographic, clinical, and imaging metrics were extracted from chart review. The prevalence of IPMN was compared between the 2 groups. RESULTS: A total of 800 patient charts were reviewed. There were 400 patients with CKD compared with an age-matched control group of 400 patients without CKD. The total prevalence of IPMN in patients with CKD was 13.7% (55/400) compared with 7.8% (29/400; P = 0.002) in non-CKD patients. The prevalence of diabetes mellitus was significantly higher in the CKD group (41% vs 14%, P = 0.0001). The percentage of patients consuming alcohol was significantly higher in the non-CKD group (23% vs 35%, P = 0.002). CONCLUSIONS: Patients with CKD have a significantly higher prevalence of IPMN compared with non-CKD patients. Larger population-based studies are needed to confirm these findings.

Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors.

BACKGROUND: Clinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence. METHODS: The data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for "mucus extension." RESULTS: The 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019). CONCLUSIONS: During the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences.

Development and validation of a nomogram for predicting survival of pulmonary invasive mucinous adenocarcinoma based on surveillance, epidemiology, and end results (SEER) database.

BACKGROUND: Lung cancer remains the leading cause of cancer death globally. In 2015, the cancer classification guidelines of the World Health Organization were updated. The term "invasive mucinous adenocarcinoma (IMA)" aroused people's attention, while the clinicopathological factors that may influence survival were unclear. METHODS: Data of IMA patients was downloaded from SEER database. Kaplan-Meier methods and log-rank tests were used to compare the differences in OS and LCSS. The nomogram was developed based on the result of the multivariable analysis. The discrimination and accuracy were tested by Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses (DCA). Integrated discrimination improvement (IDI) index was used to evaluate the clinical efficacy. RESULTS: According to multivariate analysis, the prognosis of IMAs was associated with age, differentiation grade, TNM stage and treatments. Surgery might be the only way that would improve survival. Area under the curve (AUC) of the training cohort was 0.834and 0.830 for3-and 5-year OS, respectively. AUC for 3-and 5-year LCSS were separately 0.839 and 0.839. The new model was then evaluated by calibration curve, DCA and IDI index. CONCLUSION: Based on this study, prognosis of IMAs was systematically reviewed, and a new nomogram was developed and validated. This model helps us understand IMA in depth and provides new ideas for IMA treatment.

Diabetes and Weight Loss Are Associated With Malignancies in Patients With Intraductal Papillary Mucinous Neoplasms.

BACKGROUND & AIMS: The role of diabetes in intraductal papillary mucinous neoplasms (IPMNs) is not known. We investigated the prevalence of diabetes among patients with resected IPMNs and the association between diabetes, clinical and morphological features, and high-grade dysplasia or invasive cancer. METHODS: We collected clinical, pathology, laboratory, and demographic data from 134 patients who underwent pancreatic resection for IPMN from a referral center in Germany. We identified 50 patients with diabetes (37%). RESULTS: Higher proportions of patients with diabetes were male and older, but did not have increased body mass index, compared to patients without diabetes. Diabetes was significantly associated with main-duct involvement (odds ratio [OR], 2.827; 95% CI, 1.059-7.546; P = .038) and high-grade dysplasia or invasive carcinoma (OR, 2.692; 95% CI, 1.283-5.651; P = .009). Risk of high-grade dysplasia or invasive cancer was even higher in patients with new-onset or worsening diabetes (OR, 4.615; 95% CI, 1.423-14.698; P = .011). Fifty-eight percent of patients (18/31) with weight loss at diagnosis had diabetes vs 32% of patients (31/97) without weight loss (P = .009). However, when the analysis was restricted to IPMNs with low-grade dysplasia, weight loss and diabetes were no longer associated (42% [5/12] vs 21% [9/44]; P = .133). CONCLUSIONS: In patients with IPMNs, diabetes is associated with increased risk of main duct involvement and high-grade dysplasia or invasive carcinoma. Studies are needed to determine the relationship between diabetes and progression of IPMNs, which might lead to strategies for early detection and prevention of invasive cancer. Findings from this study should be considered in the guidelines for management of IPMN.

Diabetes mellitus in intraductal papillary mucinous neoplasms: A systematic review and meta-analysis.

BACKGROUND: Our current knowledge of diabetes mellitus in intraductal papillary mucinous neoplasm is very limited and its prevalence and predictive value for malignant transformation are not clear. This study sought to systematically review the literature to define the prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm and to evaluate the association of diabetes mellitus with the progression to high-grade dysplasia or invasive cancer. METHODS: A PubMed/Medline systematic search was performed to identify studies reporting data on preoperative diabetes mellitus in intraductal papillary mucinous neoplasm. Articles meeting the predefined inclusion criteria were analyzed and a meta-analysis was performed. The study was preregistered (PROSPERO ID: CRD42020153581). RESULTS: From the initially detected 827 studies, 27 studies including resected patients with histologically confirmed intraductal papillary mucinous neoplasm were included. The global prevalence of preoperative diabetes mellitus was 25% (1,112 of 4,412); whereas new-onset/worsening diabetes mellitus was reported in 6% of patients (68 of 1,202). The meta-analysis revealed that patients with pre-existing diabetes mellitus had an increased risk of harboring a main pancreatic duct involvement (risk ratio 1.43, 95% confidence interval: 1.21-1.69, P < .001), high-grade dysplasia (risk ratio 1.27, 95% confidence interval: 1.01-1.59, P = .04), and invasive cancer (risk ratio 1.61, 95% confidence interval: 1.33-1.95, P < .001). CONCLUSION: The prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm is high, and diabetic patients demonstrate an increased risk of a more aggressive disease. Therefore, diabetes mellitus should be increasingly considered in the stratification of patients with intraductal papillary mucinous neoplasm. Further investigations to determine the mechanisms behind the association with progression should be carried out.

Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

PURPOSE: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib. MATERIALS AND METHOD: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations. RESULTS: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup. CONCLUSION: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.

Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age at Disease Onset.

Importance: The incidence of appendiceal cancer (AC) is rising, particularly among individuals younger than 50 years (early-onset AC), with unexplained etiologies. The unique spectrum of somatic cancer gene variations among patients with early-onset AC is largely undetermined. Objective: To characterize the frequency of somatic variations and genomic patterns among patients with early-onset (age <50 years) vs late-onset (age ≥50 years) AC. Design, Setting, and Participants: This cohort study included individuals aged 18 years and older diagnosed with pathologically verified AC. Cases with clinical-grade targeted sequencing data from January 1, 2011, to December 31, 2019, were identified from the international clinicogenomic data-sharing consortium American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE). Data analysis was conducted from May to September 2020. Exposures: Age at disease onset. Main Outcomes and Measures: Somatic variation prevalence and spectrum in AC patients was determined. Variation comparisons between early-onset and late-onset AC were evaluated using multivariable logistic regression with adjustment for sex, race/ethnicity, histological subtype, sequencing center, and sample type. Results: In total 385 individuals (mean [SD] age at diagnosis, 56.0 [12.4] years; 187 [48.6%] men; 306 [79.5%] non-Hispanic White individuals) with AC were included in this study, and 109 patients (28.3%) were diagnosed with early-onset AC. Race/ethnicity differed by age at disease onset; non-Hispanic Black individuals accounted for a larger proportion of early-onset vs late-onset cases (9 of 109 [8.3%] vs 11 of 276 [4.0%]; P = 0.04). Compared with patients aged 50 years or older at diagnosis, patients with early-onset AC had significantly higher odds of presenting with nonsilent variations in PIK3CA, SMAD3, and TSC2 (PIK3CA: odds ratio [OR], 4.58; 95% CI, 1.72-12.21; P = .002; SMAD3: OR, 7.37; 95% CI, 1.24-43.87; P = .03; TSC2: OR, 12.43; 95% CI, 1.03-149.59; P = .047). In contrast, patients with early-onset AC had a 60% decreased odds of presenting with GNAS nonsilent variations compared with patients with late-onset AC (OR, 0.40; 95% CI, 0.21-0.76, P = .006). By histological subtype, young patients with mucinous adenocarcinomas of the appendix had 65% decreased odds of variations in GNAS compared with late-onset cases in adjusted models (OR, 0.35; 95% CI, 0.15-0.79; P = .01). Similarly, patients with early-onset nonmucinous appendiceal adenocarcinomas had 72% decreased odds of presenting with GNAS variations vs late-onset cases, although these findings did not reach significance (OR, 0.28; 95% CI, 0.07-1.14; P = .08). GNAS and TP53 variations were mutually exclusive in ACs among early-onset and late-onset cases (P < .05). Conclusions and Relevance: In the study, AC diagnosed among younger individuals harbored a distinct genomic landscape compared with AC diagnosed among older individuals. Development of therapeutic modalities that target these unique molecular features may yield clinical implications specifically for younger patients.

Retrospective Study of the Epidemiology, Pathology, and Therapeutic Management in Patients With Mucinous Ovarian Tumors.

AIM: We sought to determine the epidemiology of mucinous ovarian tumors, the correlation between serum biomarkers and tumor status, and the outcomes of the management in different subtypes of mucinous ovarian tumors in a Chinese surgical cohort. METHODS: A total of 513 patients were enrolled from January 2009 to May 2017. The number of patients who had benign mucinous ovarian tumor, borderline mucinous ovarian tumor, or malignant mucinous ovarian tumor was pathologically quantified. All patients underwent surgery with or without postoperative adjuvant therapy. Prognosis was analyzed based on clinicopathological characteristics and the type of treatment received. Hyperthermic intraperitoneal chemotherapy efficacy and adverse effects in patients were also explored. RESULTS: In all, 383 (75%) patients were diagnosed as having benign mucinous ovarian tumor, 76 (14%) patients with borderline mucinous ovarian tumor, and 54 (5%) patients with malignant mucinous ovarian tumor. Levels of serum biomarkers increased as the tumors became more malignant. Patients with stage IA and IC (unilateral) malignant mucinous ovarian tumor who underwent fertility conserving surgery did not experience poorer prognoses when compared to those who received non-fertility conserving surgery. Hyperthermic intraperitoneal chemotherapy followed by chemotherapy significantly influenced survival rates in patients with a ruptured malignant mucinous ovarian tumor. CONCLUSIONS: Levels of serum tumor markers, carbohydrate antigen 125, carbohydrate antigen 199, carbohydrate antigen 242, and carcinoembryonic antigen may be useful in monitoring for malignant transformation. Fertility conserving surgery might be a preferable surgical procedure for patients with malignant mucinous ovarian tumor at early stage (IA and IC [unilateral]). Hyperthermic intraperitoneal chemotherapy appears to be a well-tolerated and promising postoperative adjuvant.

Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing.

BACKGROUND: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. METHODS: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. RESULTS: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. CONCLUSION: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.
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Mucinous tubular and spindle cell carcinoma of the kidney: A case series with a brief review of the literature.

BACKGROUND: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare low grade renal tumour exhibiting characteristic morphological features. We share our experience and discuss briefly, a review of the current literature. METHODS: Electronic medical records were searched between January 2005 to January 2017. The histopathology and immunohistochemistry slides were retrieved and reviewed. RESULTS: Eleven cases of MTSCC were identified. Mean age at presentation was 53.9 (age range 41 to 71) years with a slight female preponderance (F: M=6:5). Clinical stage at presentation was: Stage I (4 cases), Stage II (3 cases), Stage III (1 case), and Stage IV (3 cases). The average tumour size was 7.5cm (range 3.5 to 17cm). Microscopically, characteristic biphasic tumour with tubular and spindle cell morphology with variable mucinous stroma was noted in all. The prominent immunohistochemical profile revealed positivity for CK7 (7/8, 87.5%), AMACR (6/8, 75%), AE1/3 (4/4, 100%), CD10 (3/10, 27.3%), and Vimentin (3/3, 100%). Seven patients (Stage I and II) had been treated with nephrectomy, whereas only a diagnostic biopsy was available in four patients who presented with locally advanced disease (n=1) or distant metastasis (n=3) at presentation. The mean follow-up was 37.8 months (range 8 to 96 months), available in 10 out of 11 patients, without recurrence in nine while one died 8 months after diagnosis. CONCLUSION: MTSCC is an indolent renal cancer with characteristic morphology. However, presentation with locally advanced disease or distant metastasis may be seen in a subset of these patients. This warrants close follow-up in even localized tumors.