Development and validation of a decision tree for distinguishing pulmonary adenocarcinomas with mucinous features and metastatic colorectal adenocarcinoma.

BACKGROUND: Diagnosis of mucinous carcinomas in the lung on transbronchial biopsy or fine-needle aspiration (FNA) samples can be difficult for the pathologist, because primary and metastatic tumors can have similar morphological, immunohistochemical, and molecular characteristics. Correct diagnosis is key to determine appropriate therapy and to distinguish primary from metastatic disease. This distinction often falls to the pathologist in patients with a history of mucinous adenocarcinoma of the colon. Despite its drawbacks, immunohistochemistry is often employed to help assign a primary site for mucinous adenocarcinomas in the lung. However, the published data in this regard is limited to studies that use only a handful of markers. METHODS: The authors examined the staining characteristics and heterogeneity of CK7, TTF-1, NapsinA, CK20, CDX2, and SATB2 in resection specimens of pulmonary adenocarcinomas with mucinous features and metastatic colorectal adenocarcinoma. RESULTS: Based on the heterogeneity, sensitivity, and specificity in this cohort, the authors developed a decision tree based on TTF-1, SATB2, CDX2, and CK7 to categorize tumors as primary or metastatic lesions. Validation of the decision tree in FNA specimens from the lungs and lung-draining lymph nodes showed 84% concurrence in cases from the lung and 100% concurrence in cases from the lymph node. In cases where the algorithm assigned a primary site, it was 95% accurate compared to the multidisciplinary diagnosis. CONCLUSIONS: This method holds promise in distinguishing primary versus metastatic lesions in resection, biopsy, and FNA samples from the lungs.

A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms.

BACKGROUND: There is a paucity of targeted therapies for patients with pseudomyxoma peritonei (PMP) secondary to low-grade appendiceal mucinous neoplasms (LAMNs). Dysregulated metabolism has emerged as a hallmark of cancer, and the relationship of metabolomics and cancer is an area of active scientific exploration. We sought to characterize phenotypic differences found in peritoneal metastases (PM) derived from LAMN versus adenocarcinoma. METHODS: Tumors were washed with phosphate-buffered saline (PBS), microdissected, then dissociated in ice-cold methanol dried and reconstituted in pyridine. Samples were derivatized in tert-butyldimethylsilyl (TBDMS) and subjected to gas chromatography-coupled mass spectrometry. Metabolites were assessed based on a standard library. RNA sequencing was performed, with pathway and network analyses on differentially expressed genes. RESULTS: Eight peritoneal tumor samples were obtained and analyzed: LAMNs (4), and moderate to poorly differentiated adenocarcinoma (colon [1], appendix [3]). Decreases in pyroglutamate, fumarate, and cysteine in PM from LAMNs were found compared with adenocarcinoma. Analyses showed the differential gene expression was dominated by the prevalence of metabolic pathways, particularly lipid metabolism. The gene retinol saturase (RETSAT), downregulated by LAMN, was involved in the multiple metabolic pathways that involve lipids. Using network mapping, we found IL1B signaling to be a potential top-level modulation candidate. CONCLUSIONS: Distinct metabolic signatures may exist for PM from LAMN versus adenocarcinoma. A multitude of genes are differentially regulated, many of which are involved in metabolic pathways. Additional research is needed to identify the significance and applicability of targeting metabolic pathways in the potential development of novel therapeutics for these challenging tumors.

Pancreatic Cystic Lesions: Next Generation of Radiologic Assessment.

Pancreatic cystic lesions are frequently identified on cross-sectional imaging. As many of these are presumed branch-duct intraductal papillary mucinous neoplasms, these lesions generate much anxiety for the patients and clinicians, often necessitating long-term follow-up imaging and even unnecessary surgical resections. However, the incidence of pancreatic cancer is overall low for patients with incidental pancreatic cystic lesions. Radiomics and deep learning are advanced tools of imaging analysis that have attracted much attention in addressing this unmet need, however, current publications on this topic show limited success and large-scale research is needed.

Real-world costs and dynamics of surveillance in patients who underwent surgery for low-risk branch duct intraductal papillary mucinous neoplasms.

Surveillance costs and appropriateness of surgery of "low-risk" BD-IPMNs are relevant issues. In this study we evaluated the rate of correct indication for pancreatectomy defined as high grade dysplasia (HGD) at histology in 961 patients who underwent surveillance for a median of 5.1 years. Undertreatment and overtreatment were defined as invasive cancer and low grade dysplasia (LGD) at histology, respectively. Of the 66 patients (6.9%) who were operated, only 16 (23.8%) had a HGD while 40 (59.7%) had a LGD and 10 (14.9%) an invasive cancer, without differences regarding timing of surgery. The mean surveillance cost was € 194.9 ± 107.6 per patient-year, with a median cost of € 277.1 ± 148.2 in the correct surgery group compared with € 222.7 ± 111.6 and € 197 ± 102.7 in the overtreatment and undertreatment groups. The surveillance mean cost from diagnosis to surgery was € 854.8. Rate of appropriate surgery in BD-IPMNs under surveillance is low.

Outcome-based Validation of Confluent/Expansile Versus Infiltrative Pattern Assessment and Growth-based Grading in Ovarian Mucinous Carcinoma.

The growth pattern (confluent/expansile versus infiltrative) in primary ovarian mucinous carcinoma (OMC) is prognostically important, and the International Collaboration on Cancer Reporting (ICCR) currently recommends recording the percentage of infiltrative growth in this tumor type. Histologic grading of OMC is controversial with no single approach widely accepted or currently recognized by the World Health Organization Classification of Tumours. Since ovarian carcinoma grade is often considered in clinical decision-making, previous literature has recommended incorporating clinically relevant tumor parameters such as growth pattern into the OMC grade. We herein validate this approach, termed Growth-Based Grade (GBG), in an independent, well-annotated cohort from 2 institutions. OMCs with available histologic material underwent review and grading by Silverberg, International Federation of Obstetrics and Gynecology (FIGO), and GBG schema. GBG categorizes OMCs as low-grade (GBG-LG, confluent/expansile growth, or ≤10% infiltrative invasion) or high-grade (GBG-HG, infiltrative growth in >10% of tumor). The cohort consisted of 74 OMCs, 53 designated as GBG-LG, and 21 as GBG-HG. Using Silverberg grading, the cohort had 42 (57%) grade 1, 28 (38%) grade 2, and 4 (5%) grade 3 OMCs. Using FIGO grading, 50 (68%) OMCs were grade 1, 23 (31%) grade 2, and 1 (1%) grade 3. Follow-up data was available in 68 patients, of which 15 (22%) had cancer recurrence. GBG-HG tumors were far more likely to recur compared with GBG-LG tumors (57% vs. 6%; χ 2P <0.0001). Silverberg and FIGO grading systems also correlated with progression-free survival in univariate analysis, but multivariate analysis showed only GBG to be significant (hazard ratio: 10.9; Cox proportional regression P =0.0004). Seven patients (10%) died of disease, all of whom had GBG-HG (log-rank P <0.0001). Multivariate analysis showed that the percentage of infiltrative growth was the only factor predictive of disease-specific survival (hazard ratio: 25.5, Cox P =0.02). Adding nuclear atypia to GBG categories did not improve prognostication. Our study validates the prognostic value of the GBG system for both disease-free survival and disease-specific survival in OMC, which outperformed Silverberg and FIGO grades in multivariate analysis. Thus, GBG should be the preferred method for tumor grading.

Value of the log odds of positive lymph nodes for prognostic assessment of colon mucinous adenocarcinoma: Analysis and external validation.

PURPOSE: To evaluate the impact of the log odds of positive lymph nodes (LODDS) on cancer-specific survival (CSS) in colon mucinous adenocarcinoma (MAC) patients, compared with pN stage and the lymph nodes ratio (LNR). METHODS: A total of 10,182 colon MAC patients from the Surveillance, Epidemiology, and End Results database were divided into the training group. The external validation group included 153 patients from Fujian Medical University Union Hospital. The Cox regression method was used to identify prognostic risk factors. Nomograms were evaluated by Harrell's concordance index (C-index) and calibration curves. Recursive partitioning analysis (RPA) was used to develop a novel staging system. RESULTS: Time-dependent receiver operating characteristic curves (ROC) to predict CSS showed the areas under the ROC curve of LODDS were always higher than pN stage and LNR. LNR and LODDS classifications can well distinguish the prognosis of patients with the same pN stage. Cox analyses indicated that age, tumor size, pT stage, pN stage, LNR, and LODDS were independent predictors of CSS (p < 0.05). Based on three lymph nodes classifications, we constructed three prognostic nomograms models for CSS. The C-index of the pN, LNR, and LODDS classification nomograms were 0.746 (95% confidence interval [95% CI]: 0.736-0.756), 0.750 (95% CI: 0.740-0.760), and 0.758 (95% CI: 0.748-0.768), respectively. In external validation, we observed the C-index of LODDS classification nomograms was 0.787 (95% CI: 0.648-0.926). RPA stage, including four stages, was constructed successfully based on pT stage and LNR or LODDS, respectively. The 3-, 5-, and 8-year areas under the ROC curve of LNR-RPA stage and LODDS-RPA stage were superior to tumor-node-metastasis stage. CONCLUSION: LODDS to be a better prognostic factor of CSS for colon MAC patients than pN stage and LNR. A nomogram and RPA stage base on LODDS can provide accurate information for personalized cancer treatment.

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.

Macroscopic and microscopic characteristics of low grade appendiceal mucinous neoplasms (LAMN) on appendectomy specimens and correlations with pseudomyxoma peritonei development risk.

Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development. Our major findings include: (1) As compared to those without PMP, the cases that developed PMP were more frequent to have (a) smaller luminal diameter (<1 cm) and thicker wall, separate mucin aggregations, and microscopic perforation/rupture, all suggestive of luminal mucin leakage; (b) microscopic acellular mucin presenting on serosal surface and not being confined to mucosa; and (c) neoplastic epithelium dissecting outward beyond mucosa, however, with similar frequency of neoplastic cells being present in muscularis propria. (2) Involvement of neoplastic cells or/and acellular mucin at surgical margin did not necessarily lead to tumor recurrence or subsequent PMP, and clear margin did not absolutely prevent PMP development. (3) Coexisting diverticulum, resulted from neoplastic or non-neoplastic mucosa being herniated through muscle-lacking vascular hiatus of appendiceal wall, was seen in a quarter of LAMN cases, regardless of PMP. The diverticular portion of tumor involvement was often the weakest point where rupture occurred. In conclusion, proper evaluation of surgical specimens with search for mucin and neoplastic cells on serosa and for microscopic perforation, which are of prognostic significance, should be emphasized.

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.

Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery.

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery.

Radiological and Pathological Assessment of the 2017 Revised International Association of Pancreatology Consensus Guidelines for Intraductal Papillary Mucinous Neoplasm, With an Emphasis on the Gastric Pyloric Gland Type.

OBJECTIVES: This study aimed to assess the pitfalls of the current International Association of Pancreatology guidelines (IAPCG2017) for pancreatic intraductal papillary mucinous neoplasm (IPMN) and identify the criteria for future guidelines. METHODS: Eighty surgically resected, consecutive IPMN cases were analyzed. Data including tumor site, IPMN duct type, and surgery type were collected. Based on radiological data, cases were retrospectively classified as high-risk stigmata (HRS) and non-HRS. Pathological grades and histological subtypes of IPMN cases were determined. Severe stromal sclerosis of the IPMN septa/marked parenchymal atrophy in the upstream pancreas was investigated pathologically. Positive/negative predictive values of the IAPCG2017 were calculated. Clinicopathological features of HRS-benign cases (pathologically benign IPMN cases meeting the HRS criteria) were extracted. RESULTS: The positive/negative predictive values were 72.7%/64.0%, 70.0%/34.6%, and 54.0%/63.3% for IAPCG2017, HRS-main pancreatic duct, and HRS-nodule criteria, respectively. The 15 HRS-benign cases (18.8%) included 13 pancreatoduodenectomies and 10 cases of gastric pyloric (GP) gland subtype. Severe upstream atrophy was significantly related to IPMN malignancy, unlike the severe sclerosis of IPMN septa. CONCLUSIONS: Benign IPMNs of GP subtype are sometimes categorized as HRS with the IAPCG2017. Collecting data on the natural course of GP-IPMN is necessary. To evaluate upstream atrophy may be of value to predict IPMN malignancy.

Pattern and Significance of Tumour Budding in Colorectal Carcinomas Using ITBCC Guidelines: a Low Resource Setting Practice Observation.

PURPOSE: To determine the pattern and significance of tumour budding among colorectal carcinoma (CRC) Nigerian patients using the 2016 International Tumour Budding Consensus Conference (ITBCC) guidelines. METHODS: H&E-stained slides of resected CRC at the University College Hospital and a private laboratory, both in Ibadan, Nigeria, from January 2008 to December 2017 were reviewed. Patient age, gender, tumour size and location were obtained from the surgical pathology records. Tumours were graded and staged according to the 2010 WHO and the 2017 UICC protocols, respectively. Tumour budding was determined at × 20 objective lens magnification with a 20-mm eyepiece field number diameter. Descriptive, Mann-Whitney U and chi-square test statistics were applied using SPSS 20; p < 0.05 was considered significant. RESULTS: Ninety-six cases were included in this study. Fifty-one (53.1%) showed tumour budding. Tumour bud count was low (0-4) in 66 (68.8%), intermediate (5-9) in 12 (12.5%) and high (≥ 10) in 18 (18.8%) tumours. Four tumours had pT1 stage, 35 pT2, 37 pT3 and 20 pT4. Forty-three (44.8%) tumours were lymph node-positive, and 10 (10.4%) had metastasis. Patients' age and tumour size distribution were similar in the tumour budding and non-budding groups (52.4 ± 17.1/58.5 ± 13.9 years and 6.6 ± 2.9/6.6 ± 2.8 cm, respectively). There was significant association between tumour budding and tumour grade (p < 0.008), pT stage (p < 0.000), lymphovascular permeation (p < 0.000), perineural invasion (p < 0.003) and nodal status (p < 0.034), but not with gender (p = 0.588), metastasis (p = 0.327) and TNM group-stage (p = 0.062). CONCLUSION: Tumour budding frequency is high among our CRC patients and is associated with poorer prognostic factors.

Preoperative Radiographic Assessment Predicts Incomplete Cytoreduction in Patients with Low Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for patients with low-grade mucinous adenocarcinoma (LGMA) is most effective when complete cytoreduction is achieved. We externally validated two radiographic scoring systems to predict resectability and assessed radiographic response to systemic chemotherapy (SCT). METHODS: Patients with LGMA who received preoperative SCT followed by CRS/HIPEC from 2013 to 2016 were identified. CT scans were graded by six physicians using the simplified radiologic score (SRS) and simplified preoperative assessment of appendiceal tumor (SPAAT) systems. Positive and negative predictive values (PPV, NPV) were calculated by comparing to completeness of cytoreduction. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients had preoperative SCT followed by CRS/HIPEC. Thirteen patients underwent incomplete CRS and 11 patients complete CRS. Scoring of the preoperative CT had a PPV of complete cytoreduction of 75% and 66.7% for SRS and SPAAT, respectively. NPV was 83.4% and 88.9% for SRS and SPAAT, respectively. ICC for the preoperative SRS and SPAAT score was 0.826 (95% confidence interval [CI]: 0.720-0.910] and 0.788 [0.667-0.888). Comparison of CT scans before and after SCT recorded an increase in calculated scores in 45.8% (SRS) and 50% (SPAAT) of patients. CONCLUSIONS: External validation of two radiographic scoring systems to predict complete cytoreduction showed that inter-rater agreement for both systems was good. Both scoring systems predicted incomplete cytoreduction. Applying a systematic approach to preoperative imaging review is recommended to improve treatment selection by minimizing morbidity associated with incomplete CRS and help to set patient expectations.

Impact of different adjuvant radiotherapy modalities on women with early-stage intermediate- to high-risk endometrial cancer.

OBJECTIVE: Vaginal brachytherapy was recommended for patients with intermediate-risk endometrial cancer, however, optimal radiotherapy modalities for intermediate-high- or high-risk patients remains controversial. Previous studies have mainly focused on survival outcomes and have seldom taken cost issues into consideration, especially for high-risk patients. The purpose of this study is to compare the survival outcomes and costs associated with two adjuvant radiotherapy modalities in the management of patients with early-stage, intermediate- to high-risk endometrial cancer. METHODS: According to ESMO-ESCO-ESTRO criteria, 238 patients with stage I/II, intermediate- to high-risk endometrial cancer who underwent radiotherapy from January 2003 to December 2015 at our institution were reviewed. The vaginal brachytherapy group and external beam radiation therapy combined with the vaginal brachytherapy group were propensity score-matched at a 1:1 ratio. The Kaplan-Meier method and Cox proportional hazards regression model were used. RESULTS: A total of 361 patients met our inclusion criteria, the median age of the patients was 58 years (range, 28-85). All were diagnosed with stage I-II endometrial cancer (324 with stage I and 37 with stage II; 350 with endometrioid adenocarcinoma; and 10 with mucinous carcinoma). The median follow-up time was 60.5 months (range, 3-177). Among 119 matched pairs, no significant differences were found in overall (10.9% vs 8.4%, P=0.51), locoregional (4.2% vs 1.7%, P=0.45), or distant recurrence rates (6.7% vs 6.7%, P=1.0) between the two groups. There were also no differences in the 5-year overall (94.8% vs 93.9%, P=0.78) or progression-free survival (90.0% vs 84.4%, P=0.23) between the two groups. The rates of acute and late toxicity were significantly higher in the external beam radiation therapy combined with vaginal brachytherapy vs the vaginal brachytherapy group (all P<0.05), except for the acute hematological toxicity rate (17.6% vs 9.2%, P=0.06). External beam radiation therapy combined with vaginal brachytherapy had a higher median cost ($2759 vs $937, P<0.001) and longer median radiotherapy duration (41 days vs 17 days, P<0.001) than vaginal brachytherapy. CONCLUSION: Vaginal brachytherapy was associated with similar local control and long-term survival outcomes relative to the combination of external beam radiotherapy and vaginal brachytherapy and it also minimizes radiation-related complications, reduces medical costs, and shortens radiotherapy duration. Vaginal brachytherapy may be the optimal radiation modality for patients with early-stage endometrial cancer at intermediate to high risk.

Quantitative MRI assessment of mucinous rectal adenocarcinoma to predict tumour response after neoadjuvant therapy.

AIM: To evaluate the association between volume ratio of the mucus pool and tumour response to neoadjuvant therapy in patients with mucinous rectal adenocarcinoma (MC). MATERIALS AND METHODS: The volume of the mucus pool and whole tumour on pre-therapeutic T2-weighted magnetic resonance imaging (MRI) of 79 patients was measured using semi-automated software. Mucus pool volume, whole tumour volume, and volume ratio of the mucus pool were compared to tumour response and tumour and lymph node downstaging after neoadjuvant therapy using receiver operating characteristic curve (ROC) and multivariate logistic regression analysis. RESULTS: After preoperative neoadjuvant therapy of rectal MC, the rate of pathological complete response, tumour downstaging, tumour response, and lymph node downstaging were 9%, 48%, 39% and 58%, respectively. Tumour downstaging more frequently occurred in patients with a mucus pool volume ratio of at least 68.3% (area under the ROC curve [AUC], 0.793 with 95% confidence interval [CI]: 0.693-0.893), and at least 62.1% for identifying those with a higher tumour response with an AUC of 0.739 (95% CI: 0.630-0.847). CONCLUSION: A higher volume ratio of mucus pool in patients with MC may be related to more tumour downstaging and therapy response, and therefore, could serve as an independent imaging biomarker for predicting tumour response to neoadjuvant therapy.

Assessment of the clinicopathological relevance of mesothelin level in plasma, peritoneal fluid, and tumor tissue of epithelial ovarian cancer patients.

Ovarian cancer remains the most lethal gynecologic malignancy. This is due to lack of effective screening, diagnosis predominance in late stage of disease, a high recurrence rate after primary therapy, and poor treatment response in platinum-resistant tumor. Thus, unique biomarkers, predictive of individual disease course, and prognosis are urgently needed. The aim of our study was to assess the clinicopathological significance of plasma, peritoneal fluid, and tumor tissue levels of mesothelin in epithelial ovarian cancer patients. Plasma and peritoneal fluid levels of mesothelin were measured by enzyme-linked immunosorbent assay. Tissue expression of MSLN was evaluated using quantitative real-time polymerase chain reaction. Preoperative plasma mesothelin levels were significantly higher in epithelial ovarian cancer patients in comparison to the patients with benign tumor and controls. There have been noticed significant differences in the plasma mesothelin levels based on International Federation of Gynecology and Obstetrics stage, grade, and histology type. No significant changes were observed between Kurman and Shih type I versus type II epithelial ovarian cancer. Interestingly, peritoneal fluid mesothelin levels revealed significant differences based on both grade and Kurman and Shih-type epithelial ovarian cancer. There were no relevant changes in the mesothelin level in peritoneal fluid between different stages and histology types compared to benign tumor. MSLN expression level in tumor tissue was significantly higher based on stage, grade, and Kurman and Shih-type epithelial ovarian cancer than in the benign masses. In addition, data showed significant higher MSLN expression in endometrioid tumors compared to benign masses and serous tumors. Plasma, peritoneal fluid, and tumor tissue levels of mesothelin positively correlated with level of CA125. Low mesothelin concentrations in plasma were also associated with prolonged patient survival. More importantly, we revealed that plasma mesothelin level was correlated with both peritoneal fluid mesothelin level and tumor MSLN expression. This study highlights that plasma mesothelin level may be a useful noninvasive biomarker surrogate for local tumor mesothelin status in monitoring of epithelial ovarian cancer patients.

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort.

OBJECTIVES: To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images. METHODS: Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed. RESULTS: Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm3 and 9.4 cm3, respectively). CONCLUSIONS: Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers. KEY POINTS: • MRI measurements by different radiologists can be used for IPMN follow-up. • Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility. • Manual axial measurements show the highest interobserver reproducibility in determining size. • Axial and coronal volume measurements show similar limits of agreement. • Manual axial measurements show the lowest variability in agreement range.

Diagnostic Usefulness of Combination of Diffusion-weighted Imaging and T2WI, Including Apparent Diffusion Coefficient in Breast Lesions: Assessment of Histologic Grade.

PURPOSE: This study aimed to compare the diagnostic values of a combination of diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to evaluate the correlation of DWI with the histologic grade in breast cancer. MATERIALS AND METHODS: This study evaluated a total of 169 breast lesions from 136 patients who underwent both DCE-MRI and DWI (b value, 1000s/mm2). Morphologic and kinetic analyses for DCE-MRI were classified according to the Breast Imaging-Reporting and Data System. For the DWI-T2WI set, a DWI-T2WI score for lesion characterization that compared signal intensity of DWI and T2WI (benign: DWI-T2WI score of 1, 2; malignant: DWI-T2WI score of 3, 4, 5) was used. The diagnostic values of DCE-MRI, DWI-T2WI set, and combined assessment of DCE and DWI-T2WI were calculated. RESULTS: Of 169 breast lesions, 48 were benign and 121 were malignant (89 invasive ductal carcinoma, 24 ductal carcinoma in situ, 4 invasive lobular carcinoma, 4 mucinous carcinoma). The mean apparent diffusion coefficient (ADC) of invasive ductal carcinoma (0.92 ± 0.19 × 10-3 mm2/s) and ductal carcinoma in situ (1.11 ± 0.13 × 10-3 mm2/s) was significantly lower than the value seen in benign lesions (1.36 ± 0.22 × 10-3 mm2/s). The specificity, positive predictive value (PPV), and accuracy of DWI-T2WI set and combined assessment of DCE and DWI-T2WI (specificity, 87.5% and 91.7%; PPV, 94.3% and 96.2%; accuracy, Az = 0.876 and 0.922) were significantly higher than those of the DCE-MRI (specificity, 45.8%; PPV, 81.7%; accuracy, Az = 0.854; P < .05). A low ADC value and the presence of rim enhancement were associated with a higher histologic grade cancer (P < .05). CONCLUSION: Combining DWI, T2WI, and ADC values provides increased accuracy for differentiation between benign and malignant lesions, compared with DCE-MRI. A lower ADC value was associated with a higher histologic grade cancer.

Uptodate in the assessment and management of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal Papillary Mucinous Neoplasms (IPMNs) are the most common cystic tumors of the pancreas and are considered premalignant lesions. IPMNs are characterized by the papillary growth of the ductal epithelium with rich mucin production, which is responsible for cystic segmental or diffuse dilatation of the main pancreatic duct (MPD) and/or its branches. According to the different involvement of pancreatic duct system, IPMNs are divided into main duct type (MD-IPMN), branch duct type (BD-IPMN), and mixed type (MT-IPMN). IPMNs may be incidentally discovered in asymptomatic patients, particularly in those with BD-IPMNs, when imaging studies are performed for unrelated indications. The increase in their frequency may reflect the combined effects of new diagnostic techniques, the improvement of radiologic exams and progress in the recognition of the pathology. MD-IPMNs present a higher risk of malignant progression than BD-IPMNs; as a consequence, all the guidelines strictly suggest the need of surgery for MD- and MT- IPMNs with MPD > 10 mm, while the management of BD-IPMNs is still controversial and depends on several cysts and patients features. The choice between non-operative and surgical management depends on the distinction between benign and invasive IPMN forms, assessment of malignancy risk, patient's wellness and its preferences. This manuscript revises the different guidelines for the management of IPMNs that have been published in different world countries: the international (Sendai 2006 and Fukuoka 2012), the 2013 European, the 2014 Italian, and finally the 2015 American guidelines. In summary, this review will integrate the recent insights in the combination of diagnostic techniques, such as Magnetic Resonance Imaging (MRI) and endoscopic ultrasound (EUS), pathology classification, and management of IPMNs.