Validation of American Joint Committee on Cancer 8th edition of TNM staging in resected distal pancreatic cancer

BACKGROUND In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma (PDAC), the American Joint Committee on Cancer (AJCC) has published its eighth edition staging manual. Some major changes have been introduced in the new staging system for both T and N categories. Given the rarity of resectable disease, distal pancreatic cancer is likely underrepresented in the published clinical studies, and how the impact of the staging system actually reflects on to clinical outcomes remain unclear. AIM To validate the AJCC 8th edition of TNM staging in distal PDAC. METHODS A retrospective cohort study was performed in seven academic medical centers in the United States. Clinicopathological prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated through univariate and multivariate analyses. RESULTS Overall, 454 patients were enrolled in the study, and were divided into 2 subgroups: Invasive intraductal papillary mucinous neoplasms (IPMN) (115 cases) and non-IPMN associated adenocarcinoma (339 cases). Compared to invasive IPMN, non-IPMN associated adenocarcinomas are more common in relatively younger patients, have larger tumor size, are more likely to have positive lymph nodes, and are associated with a higher tumor (T) stage and nodal (N) stage, lymphovascular invasion, perineural invasion, tumor recurrence, and a worse PFS and OS. The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual, and it’s more evenly distributed based on 8th edition staging manual. T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort, although dividing into N1 and N2 according to the 8th edition does not show additional stratification. For PDAC arising in IPMN, T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS. For PDAC without an IPMN component, T staging from both versions fails to stratify PFS and OS. CONCLUSION The AJCC 8th edition TNM staging system provides even distribution for the T staging, however, it does not provide better risk stratification than previous staging system for distal pancreatic cancer

Colorectal Microcarcinoids in Association with Long-Term Exposure to Urinary Content: A Case Report and Review of the Literature

Long-term exposure of colonic mucosa to urinary content and its association with increased risk of infection, mechanical and biochemical irritation, and malignancy have been described in the literature. Existing case reports and studies depict the low but distinct risk of malignancy in gastrointestinal segments which come in contact with urinary content as a result of surgical correction of urinary tract abnormalities. However, these reports are largely limited to colonic adenocarcinoma and urothelial cell carcinoma. Late urointestinal carcinoma in patients with ileal incorporation into the urinary tract has also been reported. To the best of our knowledge, however, there is only one case report documenting neuroendocrine (NE) cell hyperplasia in colonic mucosa after long-term cystoplasty. Our case is the first to describe microcarcinoids and diffuse NE hyperplasia occurring in a patient with congenital anorectal anomalies, resulting in long-term exposure of colonic mucosa to fecal stream and urinary content. This case, in conjunction with the reported cases in the literature, raises the distinct possibility of an association between exposure of colonic mucosa to urine and long-term development of malignancy, including NE neoplasms

Pax8 as a useful adjunct marker to differentiate pancreatic serous cystadenoma from clear cell renal cell carcinoma in both cytologic and surgical specimens

Abstract Background Histomorphological differentiation between pancreatic serous cystadenoma (SCA) and clear cell renal cell carcinoma (RCC) can be challenging. We aimed to study Paired box 8 protein (Pax8) expression profile in cytologic and surgical specimens with pancreatic SCA to assess its utility as a differentiating marker from clear cell RCC. Methods We characterized Pax8 immunohistochemistry in 33 patients with pancreatic SCA (23 surgical resections and 10 cytology specimens). Nine cytology specimens from metastatic clear cell RCC involving pancreas were used as control tissue. Electronic medical records were reviewed to retrieve clinical information. Results All 10 pancreatic SCA cytology specimens, and 16 of 23 pancreatic SCA surgical resections showed absent Pax8 immunostaining, while the remaining 7 surgical resection specimens showed 1%-2% immunoreactivities. Islet and lymphoid cells adjacent to the pancreatic SCA expressed Pax8. In contrast, the proportion of Pax8 immunoreactivity ranged from 50 to 90% (average of 76%) in nine cases of metastatic clear cell RCC involving pancreas. Using a 5% immunoreactivity cutoff, all cases of pancreatic SCA are interpreted as negative for Pax8 immunostains while all cases of metastatic clear cell RCC involving pancreas are interpreted as positive for Pax8 immunostains. Conclusions These results suggest that Pax8 immunohistochemistry staining can be a useful adjunct marker to differentiate pancreatic SCA from clear cell RCC in clinical practice. To the best of our knowledge, this is the first large-scale study of Pax8 immunostaining on surgical and cytology specimens with pancreatic SCA

Measuring depth of invasion of submucosa- - - invasive adenocarcinoma in oesophageal endoscopic specimens: how good are we?-

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171205/1/his14566.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171205/2/his14566_am.pd

Challenges with colorectal cancer staging: results of an international study

Challenges exist with standardized colorectal cancer reporting despite adoption of the American Joint Committee on Cancer-Staging Manual 8th edition. We performed this study to gauge current practice patterns among a diverse group of surgical pathologists. A web-based questionnaire depicting problematic issues and images related to colorectal carcinoma staging was circulated among 118 surgical pathologists and their responses were correlated with their geographic location (North America vs. Europe vs. others), nature of practice (academic vs. community), the sign-out model (gastrointestinal subspecialty vs. general surgical pathology), and years of professional experience. We found that a substantial number of practicing pathologists ignore recommended-staging criteria in specific settings, particularly with respect to assessment of advanced T stage. Tumors that communicated with the serosa through inflammatory foci were staged as pT3 (49%) or pT4a (51%) by nearly equal numbers of pathologists regardless of level of experience, the sign-out model, or geographic location. Only 65% assigned T stage and margin status based on extent of viable tumor in the neoadjuvant setting. One-third of pathologists, particularly those in Europe (p = 0.015), classified acellular mucin deposits as N1 disease when detected in treatment-naive cases. Nearly 50% of pathologists classified isolated tumor cells (i.e., deposits <0.2 mm) in lymph nodes as metastatic disease (i.e., pN1, p = 0.02). Our results suggest that pathologists ignore recommendations that are based on insufficient data and apply individualized criteria when faced with situations that are not addressed in the American Joint Committee on Cancer Staging Manual 8th edition. These variations in practice limit the ability to compare outcome data across different institutions and draw attention to areas that require further study

Interobserver Agreement in the Diagnosis of Inflammatory Bowel Disease-Associated Neoplasia in China in Comparison to Subspecialized American Gastrointestinal Pathologists

Background. The aim of this study was to evaluate the interobserver variability in diagnosing inflammatory bowel disease (IBD)-associated neoplasia among practicing pathologists from China using telepathology, a practice of remote diagnostic consultation increasingly used nationally and internationally, and its comparison with the interpretation of subspecialized gastrointestinal (GI) pathologists from the United States (US). Methods. Eight GI pathologists from the US and 4 pathologists from China with an interest in GI pathology participated in this study. A total of 50 colonic biopsies from patients with a clinical history of IBD from 8 medical centers in China were included. All microscopic slides in each case were digitized using an Aperio system. One pathologist (XL) reviewed the digitized full-slide images, and selected areas of interest were captured at low, medium, and high magnifications at a resolution of 1712 × 1072 pixels and saved as tagged image file format (TIFF) files on read-only DVD. Each pathologist evaluated the images and selected the most appropriate diagnostic category for each case (negative, indefinite, low-grade dysplasia [LGD], high-grade dysplasia [HGD], and carcinoma). A Fleiss’ kappa coefficient (K) analysis was performed to determine interobserver agreement and the agreement of each pathologist from China with the consensus diagnosis (defined as diagnostic agreement by at least 4 participating US GI pathologists). Results. There was substantial interobserver agreement among 4 pathologists from China on the interpretation of IBD-associated neoplasia (kappa value 0.68, 95% confidence interval: 0.56–0.78). A consensus diagnosis included negative (n=22), LGD (n=22), HGD (n=3), carcinoma (n=2), and indefinite for dysplasia (n=1). Using consensus diagnoses as references, the agreement between each pathologist from China and the consensus diagnosis was substantial with kappa values ranging from 0.75 to 0.80. Conclusions. This study reveals substantial interobserver agreement for the interpretation of colonic neoplasia in IBD using digitized images among Chinese pathologists as well as between each Chinese pathologist and a consensus diagnosis generated by US GI pathologists