An independent assessment of an artificial intelligence system for prostate cancer detection shows strong diagnostic accuracy.

Prostate cancer is a leading cause of morbidity and mortality for adult males in the US. The diagnosis of prostate carcinoma is usually made on prostate core needle biopsies obtained through a transrectal approach. These biopsies may account for a significant portion of the pathologists' workload, yet variability in the experience and expertise, as well as fatigue of the pathologist may adversely affect the reliability of cancer detection. Machine-learning algorithms are increasingly being developed as tools to aid and improve diagnostic accuracy in anatomic pathology. The Paige Prostate AI-based digital diagnostic is one such tool trained on the digital slide archive of New York's Memorial Sloan Kettering Cancer Center (MSKCC) that categorizes a prostate biopsy whole-slide image as either "Suspicious" or "Not Suspicious" for prostatic adenocarcinoma. To evaluate the performance of this program on prostate biopsies secured, processed, and independently diagnosed at an unrelated institution, we used Paige Prostate to review 1876 prostate core biopsy whole-slide images (WSIs) from our practice at Yale Medicine. Paige Prostate categorizations were compared to the pathology diagnosis originally rendered on the glass slides for each core biopsy. Discrepancies between the rendered diagnosis and categorization by Paige Prostate were each manually reviewed by pathologists with specialized genitourinary pathology expertise. Paige Prostate showed a sensitivity of 97.7% and positive predictive value of 97.9%, and a specificity of 99.3% and negative predictive value of 99.2% in identifying core biopsies with cancer in a data set derived from an independent institution. Areas for improvement were identified in Paige Prostate's handling of poor quality scans. Overall, these results demonstrate the feasibility of porting a machine-learning algorithm to an institution remote from its training set, and highlight the potential of such algorithms as a powerful workflow tool for the evaluation of prostate core biopsies in surgical pathology practices.

Implementation of Digital Pathology Offers Clinical and Operational Increase in Efficiency and Cost Savings.

CONTEXT.­: Digital pathology (DP) implementations vary in scale, based on aims of intended operation. Few laboratories have completed a full-scale DP implementation, which may be due to high overhead costs that disrupt the traditional pathology workflow. Neither standardized criteria nor benchmark data have yet been published showing practical return on investment after implementing a DP platform. OBJECTIVE.­: To provide benchmark data and practical metrics to support operational efficiency and cost savings in a large academic center. DESIGN.­: Metrics reviewed include archived pathology asset retrieval; ancillary test request for recurrent/metastatic disease; cost analysis and turnaround time (TAT); and DP experience survey. RESULTS.­: Glass slide requests from the department slide archive and an off-site surgery center showed a 93% and 97% decrease, respectively. Ancillary immunohistochemical orders, compared in 2014 (52%)-before whole slide images (WSIs) were available in the laboratory information system-and 2017 (21%) showed $114 000/y in anticipated savings. Comprehensive comparative cost analysis showed a 5-year $1.3 million savings. Surgical resection cases with prior WSIs showed a 1-day decrease in TAT. A DP experience survey showed 80% of respondents agreed WSIs improved their clinical sign-out experience. CONCLUSIONS.­: Implementing a DP operation showed a noteworthy increase in efficiency and operational utility. Digital pathology deployments and operations may be gauged by the following metrics: number of glass slide requests as WSIs become available, decrease in confirmatory testing for patients with metastatic/recurrent disease, long-term decrease in off-site pathology asset costs, and faster TAT. Other departments may use our benchmark data and metrics to enhance patient care and demonstrate return on investment to justify adoption of DP.

Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine neoplasms: A multi-institutional study.

BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic neuroendocrine neoplasms are biologically distinct entities with different therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%) have been shown to have an overlapping histology with PD neuroendocrine carcinomas. This study compared expert cytomorphologic assessments of differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health Organization classification; n = 72) were diagnosed independently by 3 cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or poorly differentiated small cell type [PD-S]) purely on the basis of cytomorphology. Their diagnoses were compared with a final classification supported by immunohistochemistry (retinoblastoma (RB), death domain- associated protein (DAXX), and α thalassemia/mental retardation syndrome X-linked (ATRX) protein expression), targeted mutation analysis (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets), prior history of G1/G2 histology, and consensus. RESULTS: The rate of agreement on differentiation was 38% (15 WD cases and 12 PD cases) for the 70 cases included (55 WD cases [n = 19 G2, n = 31 G3, and n = 5 could not be graded] and 15 PD cases [n = 6 PD-S, n = 6 PD-L, and n = 3 PD, not otherwise specified). Two cases could not be classified by the employed methods. PD carcinomas had a higher rate of agreement (10 of 15 [67%]) than WD neoplasms (15 of 55 [27%]). Round nuclei and plasmacytoid cells were associated with agreement for WD cases, whereas apoptosis and angulated nuclei were associated with disagreement. Necrosis was associated with agreement for PD cases. CONCLUSIONS: A purely morphologic approach to the distinction between G2 and G3 pancreatic neuroendocrine neoplasms based on cytology can be challenging, with disagreement found among experienced cytopathologists. Cancer Cytopathol 2018;126:44-53. © 2017 American Cancer Society.

Cytology assessment can predict survival for patients with metastatic pancreatic neuroendocrine neoplasms.

BACKGROUND: Histological features and Ki-67 index have known usefulness in predicting prognosis and guiding therapy among patients with metastatic pancreatic neuroendocrine neoplasms. Fine-needle aspiration may offer advantages for Ki-67 assessment because the technique obtains highly cellular, well-preserved specimens with the potential for broader tumor sampling. In the current study, the authors evaluated concordance for grade and differentiation between concurrent core needle biopsy and cytology preparations. Cytological features and grade then were correlated with survival. METHODS: Differentiation, grade by Ki-67 index, and correlation of these features with survival were compared between concurrent core needle biopsy and cytology specimens from 44 patients with metastatic pancreatic neuroendocrine neoplasms. RESULTS: Differentiation by cytology smear resulted in 38 cases of well (86%) and 6 cases of poor (14%) differentiation. Agreement for differentiation between smear and cell block, smear and core needle biopsy, and cell block and core needle biopsy was 88%, 94%, and 83%, respectively, and agreement for grade was 68%, 54%, and 22%, respectively. Cytology differentiation and cytology grade were found to be strong predictors of outcome with respective hazard ratios of 8.3 (95% confidence interval [95% CI], 3.1-22.1; P<.001) and 1.9 (95% CI, 1.2-2.9) for each ascending grade. The median disease-specific survival cytology projections were 121 months (95% CI, 57-185 months [estimated]) for grade 1, 45 months (95% CI, 29-87 months) for grade 2, and 19 months (95% CI, 1-44 months) for grade 3, with median survivals of 45 months and 3 months, respectively, for patients with well-differentiated and poorly differentiated neuroendocrine tumors (P<.001). CONCLUSIONS: Grading of pancreatic neuroendocrine neoplasms on cytology may not correlate exactly with concurrent core needle biopsy, but cytology differentiation and grade are predictive of survival based on stage-adjusted analysis. Cancer Cytopathol 2017;125:188-196. © 2016 American Cancer Society.

Reliable Pan-Cancer Microsatellite Instability Assessment by Using Targeted Next-Generation Sequencing Data.

PURPOSE: Microsatellite instability (MSI)/mismatch repair (MMR) status is increasingly important in the management of patients with cancer to predict response to immune checkpoint inhibitors. We determined MSI status from large-panel clinical targeted next-generation sequencing (NGS) data across various solid cancer types. METHODS: The MSI statuses of 12,288 advanced solid cancers consecutively sequenced with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets clinical NGS assay were inferred by using MSIsensor, a program that reports the percentage of unstable microsatellites as a score. Cutoff score determination and sensitivity/specificity were based on MSI polymerase chain reaction (PCR) and MMR immunohistochemistry. RESULTS: By using an MSIsensor score ≥ 10 to define MSI high (MSI-H), 83 (8%) of 996 colorectal cancers (CRCs) and 42 (16%) of 260 uterine endometrioid cancers (UECs) were MSI-H. Validation against MSI PCR and/or MMR immunohistochemistry performed for 138 (24 MSI-H, 114 microsatellite stable [MSS]) CRCs, and 40 (15 MSI-H, 25 MSS) UECs showed a concordance of 99.4%. MSIsensor also identified 68 MSI-H/MMR-deficient (MMR-D) non-CRC/UECs. Of 9,591 non-CRC/UEC tumors with MSS MSIsensor status, 456 (4.8%) had slightly elevated scores(≥3 and <10) of which 96.6% with available material were confirmed to be MSS by MSI PCR. MSI-H was also detected and confirmed in three non-CRC/UECs with low exonic mutation burden (< 20). MSIsensor correctly scored all 15 polymerase ε ultra-mutated cancers as negative for MSI. CONCLUSION: MSI status can be reliably inferred by MSIsensor from large-panel targeted NGS data. Concurrent MSI testing by NGS is resource efficient, is potentially more sensitive for MMR-D than MSI PCR, and allows identification of MSI-H across various cancers not typically screened, as highlighted by the finding that 35% (68 of 193) of all MSI-H tumors were non-CRC/ UEC.

Prospective impact of tumor grade assessment in biopsies on tumor stage and prognostic grouping in gastroesophageal adenocarcinoma: relevance of the seventh edition American Joint Committee on Cancer Staging Manual revision.

BACKGROUND: In the seventh edition of the American Joint Committee on Cancer (AJCC) staging system for esophageal cancer, tumor grade was introduced as an independent determinant of stage grouping in early stage tumors. With the significantly lower prognosis for poorly differentiated early stage adenocarcinomas, patients with these tumors may become candidates for neoadjuvant therapy given an accurate identification of these tumors with preoperative staging. The objective of the current study was to investigate the accuracy of preoperative histopathologic grading and the effect of preoperative grade on tumor stage/prognostic grouping. METHODS: Preoperative tumor grade was compared with postoperative tumor grade in 427 patients who underwent surgery without receiving neoadjuvant therapy for adenocarcinoma of the esophagus. The impact of preoperative tumor grade on stage/prognostic grouping was investigated. RESULTS: The overall accuracy of preoperative tumor grade assessment was 76% when unknown differentiation was regarded as well/moderately differentiated as recommended by the AJCC, whereas accuracy was 73% after the exclusion of tumors with unknown grade. In patients who have tumors classified as T1 or T2 and lymph node-negative (N0) (T1-T2N0) disease, 16% were assigned to a lower stage group based on preoperative pathology, whereas 5% were assigned to a higher stage group. In the T1-T2N0 group, sensitivity for detecting a poorly differentiated tumor was 0.43 (95% confidence interval [CI], 0.30-0.56), whereas specificity was 0.94 (95% CI, 0.90-0.98). CONCLUSIONS: With increasing use of neoadjuvant therapy, the accuracy of preoperative biopsy assessment has become increasingly important. In the current study, the accuracy of preoperative tumor grade assessment was 73%, leading to changes in AJCC stage/prognostic group in 21% of patients with T1-T2N0 esophageal adenocarcinomas. The authors concluded that caution should be exhibited in staging patients with esophageal adenocarcinoma based on preoperative biopsy data.

Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment.

BACKGROUND: This study evaluates the significance of tumor involvement of the liver in early T-stage tumors and lymph node (LN) metastases on outcome after R0 resection of gallbladder cancer (GBCA). METHODS: A prospectively maintained database, supplemented with review of the medical record, was used to identify patients who underwent a complete (R0) resection for GBCA. All patients underwent definitive surgical treatment at the initial operation (1 stage) or after initial noncurative cholecystectomy (incidental tumors, 2 stage), including partial hepatectomy and portal LN dissection, with or without bile duct and/or adjacent organ resection. Clinicopathological variables, including TNM stage, histologic tumor involvement of liver (residual or direct extension in the GB fossa or discontiguous disease), and the total number of regional LNs assessed were analyzed for their association with outcome. RESULTS: One hundred twenty-two patients were identified and analyzed. The median follow up period was 23 months. Liver and nodal involvement by GBCA were observed in 61 (50%) and 41(34%) patients, respectively. Among patients with T2 tumors (n = 53), 48 (91%) were incidental. Liver involvement was present in 26%, and this factor was associated with decreased recurrence-free (RFS) and disease-specific survival (DSS) compared with patients with T2 tumors without liver involvement (median RFS, 12 months vs. not reached, P = 0.004, median DSS 25 months versus not reached, P = 0.003); T1b tumors (n = 10) were not associated with liver involvement. The median total lymph node count (TLNC) was 3 (range 0-20). For the entire cohort, survival of patients classified as N0 based on TLNC < 6 was significantly worse than that of N0 patients based on TLNC ≥ 6 (median RFS, 22 months versus not reached, P < 0.001, median DSS 41 months versus not reached, P < 0.001). Liver involvement and TLNC remained significant prognostic factors in a multivariate model that included TNM stage. CONCLUSION: Resection and histologic evaluation of at least 6 lymph nodes improves risk-stratification after resection of GBCA. Incidental T2 tumors are often associated with residual liver disease and should be reclassified to reflect the adverse outcome. The data suggests a need for standardized minimum requirements for adequate surgical treatment and pathological examination.

Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification.

The Ki67 labeling index is known to correlate with survival in patients with neuroendocrine tumors (NETs). A grading scheme recently endorsed by the World Health Organization for gastroenteropancreatic NETs classifies well-differentiated NETs into 2 categories based on the Ki67 labeling index: low (G1) and intermediate grades (G2). Tumor heterogeneity is a common finding in many tumors including NETs. Metastatic NETs to the liver are often diagnosed by radiographically guided needle core biopsy from which the Ki67 index is determined, which randomly samples the lesion without being targeted to regions that may show a higher proliferative rate. Whether the Ki67 index obtained from this type of limited material represents the whole tumor has been questioned. Forty-five surgically resected liver metastases of well-differentiated NETs were retrieved. A 9 core (3 core-triplets) tissue microarray (TMA) was constructed from the paraffin blocks of each tumor, each triplet considered to represent a virtual biopsy. Immunohistochemical staining for Ki67 was performed on TMA and whole slides, and the Ki67 labeling indices were determined by digital image analysis. Correlation of the Ki67 index with patient survival was analyzed. Forty-seven percent of cases showed intratumoral heterogeneity in Ki67 index that translated into discrepant grades among subsections on the whole slide. A similar trend was recapitulated on the virtual biopsies, although to a lesser degree. When the definitive grade of the tumor was based on the highest Ki67 index identified on the whole slide, the virtual biopsies perfectly predicted G1 cases (100%), but were much less accurate for G2 cases (47.8% with 3 biopsies and 34.8% with single biopsy). Accordingly, the predictive value for G1 on the virtual biopsies was low (64.7% and 59.5% for 3 and 1 biopsy, respectively), but was perfect for G2 (100%). By Kaplan-Meier survival analysis, there was a statistically significant difference between G1 and G2 in terms of overall survival, disease-free survival, and progression-free survival when graded on either whole-slide subsections or virtual biopsies. On the whole slides, the highest Ki67 grade showed a better correlation with overall survival than the mean Ki67 grade. In summary, by image analysis, we found that about half of the NETs metastatic to the liver show intratumoral heterogeneity resulting in discrepant Ki67 grade. In most cases, in particular G1, the virtual biopsy is representative of the whole slide, but for G2 the representation is <50%. Nevertheless, grades based on virtual biopsy had statistically significant prognostic values on patient survival, and there is no clear difference between the 3 and single virtual biopsy. Ki67 staining of core biopsies usually provides an adequately reliable method of proliferation assessment for prognosis of metastatic NETs to the liver, although the choice of treatment may be affected by intratumoral grade heterogeneity.

Adequate lymph node assessment for extrahepatic bile duct adenocarcinoma.

OBJECTIVE: To examine the importance of adequate lymph node sampling in staging of extrahepatic bile duct cancer (EHBDCA). SUMMARY OF BACKGROUND DATA: The American Joint Committee on Cancer staging manual (sixth edition) states that histologic examination of at least 3 lymph nodes is required for adequate N stage determination for EHBDCA. This recommendation has not been validated; however, there has been no comparative assessment of the proximal versus distal bile duct cancer. METHODS: A total of 257 patients (144 hilar cholangiocarcinoma [HCCA] and 113 distal bile duct adenocarcinoma [DBDCA]) who underwent curative intent resection (1987-2007) were analyzed; patients with gallbladder cancer were excluded. Final disease staging, including lymph node status and total number of nodes examined (total lymph node count), was obtained from the final pathology report. Differences in disease-specific survival, according to nodal status, were compared using the log-rank test. R1 resections (n = 51) were excluded from this analysis. RESULTS: Metastasis to regional lymph nodes was noted in 89 patients (34.6%) and was an independent prognostic factor of poor survival (median disease-specific survival N0 vs. N1: 53.5 vs. 19.3 months, P < 0.0001, hazard ratio = 2.1 [95% CI: 1.4-3.2]). The median total lymph node count was 6 (range: 0-42), and was significantly lower for HCCA compared with DBDCA (median = 3 [range: 0-16] vs. 12 [range: 1-42], P < 0.001, respectively). For the entire cohort, patients who underwent R0 resection and were classified as N0, based on total lymph node count <11, had a disease-specific survival that was significantly worse than that of patients classified as N0 based on total lymph node count >or=11 (52.6 +/- 9.8 months vs. not reached, P = 0.008). The estimated optimal total lymph node count for HCCA differed from that of DBDCA (n = 7 vs. n = 11, respectively). CONCLUSIONS: Adequate lymph nodes assessment of EHBDCA, based on the current AJCC recommendations, results in understaging of these tumors. With respect to the optimal total lymph node count, HCCA, and DBDCA should be considered separately.

Immunohistochemistry as first-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel.

The utility of immunohistochemical detection of DNA mismatch repair proteins in screening colorectal cancer for hereditary nonpolyposis colorectal cancer (HNPCC) is being widely investigated. Currently, in both research and clinical settings, a 4-antibody panel that includes the 4 most commonly affected proteins (MLH1, MSH2, MSH6, and PMS2) is being used generally. On the basis of the biochemical properties of these proteins, we hypothesized that a 2-antibody panel, comprising MSH6 and PMS2, would be sufficient to detect abnormalities in all 4 proteins. We tested this hypothesis on a series of 232 colorectal carcinoma samples derived from 2 patient cohorts: (1) a prospectively accrued series of patients who were judged to carry a higher-than-average risk for HNPCC based on the revised Bethesda guidelines (n=190); and (2) a retrospective series of patients who were 40 years of age or younger (n=42). Immunohistochemical stains were regarded as negative (protein lost), when there was no nuclear labeling in tumor cells (with positive internal control). Overall, 70 of the 232 tumors demonstrated loss of at least one protein. The most common abnormality was concurrent loss of MLH1 and PMS2 (observed in 17% of the cases), followed by concurrent loss of MSH2 and MSH6 (6%). All MLH1 and MSH2-abnormal cases were also abnormal for PMS2 and MSH6, respectively, whereas 9 of 50 (18%) PMS2 and 6 of 20 (30%) MSH6-abnormal cases showed only isolated loss of PMS2 or MSH6 (with normal staining for MLH1 and MSH2). As such, our findings provide evidence that a 2-antibody panel (PMS2 and MSH6) is as effective as the current 4-antibody panel in detecting DNA mismatch repair protein abnormalities. Such a cost-effective approach carries significant implication, as immunohistochemistry is being widely used as first-line screening for HNPCC.

Clinical significance of intraoperative bile duct margin assessment for hilar cholangiocarcinoma.

BACKGROUND: Frozen section analysis of bile duct margins is often used to guide the extent of surgical resection for hilar cholangiocarcinoma (HCCA), but the usefulness of this practice is unknown. METHODS: The association between disease-specific survival (DSS) and pathologic margin status determined during and after surgical resection for HCCA was assessed retrospectively for 101 patients between 1992 and 2005. Final histopathology identified three subgroups on the basis of resection margin status: wide margin (bile duct and specimen margins negative for adenocarcinoma), narrow margin (bile duct margin negative but specimen margins positive), and positive margin (bile duct and specimen margins positive). RESULTS: On the basis of frozen section analysis alone, 90 patients were thought to have a disease-negative bile duct margin intraoperatively. Final histopathology showed that eight patients (9%) had invasive adenocarcinoma in the cuff of bile duct submitted for frozen section analysis. Of the 82 patients with negative final bile duct margins, 54 patients were categorized as having wide margins, and 28 patients had narrow margins. The median DSS for patients with wide margins was 56 months compared with 38 months for patients with narrow margins and 32 months for margin-positive patients (P = .01). CONCLUSION: Frozen section analysis of the proximal bile duct margin is misleading in 9% of patients. Among patients with HCCA who are determined to have negative duct margins intraoperatively, only 60% will have margins adequately wide enough to be associated with an improvement in DSS.

Preoperative radiographic assessment of hepatic steatosis with histologic correlation.

BACKGROUND: The adverse impact of hepatic steatosis on perioperative outcomes after liver resection is gaining recognition. But the accuracy of preoperative radiologic assessment of fatty liver disease remains unclear. The objective of this study was to correlate preoperative radiologic estimation with postoperative histologic measurement of steatosis. STUDY DESIGN: Patients who underwent partial hepatectomy between 1997 and 2001, with complete preoperative radiographic imaging and postoperative pathologic assessment of steatosis, were retrospectively analyzed. The presence of steatosis was assessed radiographically using noncontrast-enhanced CT (NCCT), contrast-enhanced CT (CCT), or MRI, using standard quantitative radiologic criteria. Repeat histologic analysis was used to quantify the extent of hepatic steatosis. RESULTS: One hundred thirty-one patients were studied. The overall sensitivity and specificity for all imaging modalities in detecting pathologically confirmed hepatic steatosis were 56% and 82%, respectively. Sensitivity and specificity for NCCT, CCT, and MRI using standard quantitative criteria were 33% and 100%, 50% and 83%, and 88%, and 63%, respectively. Increasing body mass indices adversely affected the accuracy of NCCT (p=0.002). Preoperative chemotherapy did not notably affect radiologic accuracy. CONCLUSIONS: The presence of a fatty-appearing liver on NCCT scans indicates clinically significant steatosis, but steatosis cannot be excluded based on a normal NCCT scan, particularly in obese patients. Conversely, normal MRI helps to exclude hepatic steatosis, but abnormal MRI is not a reliable indicator of fatty change. CCT is not an effective means of identifying steatosis. We conclude that, when used alone, conventional cross-sectional imaging does not consistently permit accurate identification of hepatic steatosis.

Carcinoid of the rectum risk stratification (CaRRs): a strategy for preoperative outcome assessment.

BACKGROUND: Predicting rectal carcinoid behavior based exclusively on tumor size is imprecise. We sought to identify factors associated with outcome and incorporate them into a pre-operative risk stratification scheme. METHODS: Seventy rectal carcinoid patients evaluated at our institution were identified. Demographic, clinical, and histopathologic data were collected and correlated with recurrence and survival. RESULTS: The mean age of our cohort was 53.6 years. Fifty-seven percent of patients were female. The mean tumor size was 1.3 cm (range: 0.1-5 cm). Twenty-five percent of patients had deeply invasive tumors (into the muscularis propria or deeper); an equal percentage had tumors with lymphovascular invasion (LVI) or an elevated mitotic rate (> or =2/50 HPF). Eleven patients (17%) had distant metastases at presentation. Sixty-one patients were followed for a median of 22 months (2-308 months), during which seven patients developed recurrence and seven died of disease (2/7 who developed recurrence). Poor outcome was associated with large tumor size, deep invasion, presence of LVI, and elevated mitotic rate. These factors were incorporated into a carcinoid of the rectum risk stratification (CaRRS) score. CaRRS predicted recurrence-free and disease-specific survival better than any single factor alone. CONCLUSIONS: Poor prognostic features of rectal carcinoids include: large size, deep invasion, LVI, and elevated mitotic rate. The CaRRS score incorporates these features and accurately predicts outcome. Because the CaRRS score is based upon values available on pre-operative biopsy, it can identify patients with very favorable prognosis as well as those with poor prognosis that may benefit from additional staging or surveillance.

Carcinoid of the rectum risk stratification (CaRRS): a strategy for preoperative outcome assessment.

BACKGROUND: Predicting rectal carcinoid behavior exclusively on the basis of tumor size is imprecise. We sought to identify factors associated with outcome and incorporate them into a preoperative risk stratification scheme. METHODS: Seventy patients with rectal carcinoid evaluated at our institution were identified. Demographic, clinical, and histopathologic data were collected and correlated with recurrence and survival. RESULTS: The mean age of our cohort was 53.6 years. Fifty-seven percent of patients were women. The mean tumor size was 1.3 cm (range, .1-5 cm). Twenty-five percent of patients had deeply invasive tumors (into the muscularis propria or deeper); an equal percentage had tumors with lymphovascular invasion (LVI) or an increased mitotic rate (two or more mitoses per 50 high-power fields). Eleven patients (17%) had distant metastases at presentation. Sixty-one patients were followed for a median of 22 months (range, 2-308 months), during which seven patients developed recurrence and seven died of disease (including two of seven whose disease recurred). Poor outcome was associated with large tumor size, deep invasion, presence of LVI, and increased mitotic rate. These factors were incorporated into a Carcinoid of the Rectum Risk Stratification (CaRRS) score. CaRRS predicted recurrence-free and disease-specific survival better than any single factor alone. CONCLUSIONS: Poor prognostic features of rectal carcinoids include large size, deep invasion, LVI, and increased mitotic rate. The CaRRS score incorporates these features and accurately predicts outcome. Because the CaRRS score is based on values available by preoperative biopsy, it can identify patients with favorable prognosis and those with poor prognosis who may benefit from additional staging or surveillance.

Perihepatic lymph node assessment in patients undergoing partial hepatectomy for malignancy.

OBJECTIVE: To assess the value of preoperative imaging studies and the intraoperative assessment of perihepatic lymph nodes in patients undergoing partial hepatectomy for malignancy. SUMMARY BACKGROUND DATA: Perihepatic lymph node status is an important prognostic factor for patients undergoing hepatic resection for 1(o) and metastatic cancer. The value of preoperative imaging studies and intraoperative assessment of perihepatic nodes is unknown. METHODS: Perihepatic lymph nodes were sampled in 100 patients undergoing resection for 1(o) and metastatic hepatic malignancy. At the time of sampling, participating surgeons assigned a clinical suspicion score (scale, 1-5: 1 = clinically negative, 5 = clinically positive). Preoperative CT scans and PET scans were reviewed in a blinded fashion by 2 radiologists. Clinical assessment, CT, and PET scan results were analyzed in the context of the pathologic status of the lymph nodes. RESULTS: A mean of 3.2 +/- 0.2 nodes were sampled per patient. Fifteen patients had metastatic disease in perihepatic lymph nodes; 13 had suggestive findings on preoperative CT or PET, and 2 were clinically positive at exploration. Clinical assessment had a high negative predictive value (NPV) = 99% but a low positive predictive value (PPV) = 39%. Similarly, CT scans had a high NPV = 95% and a low PPV = 30%. PET scans had a NPV = 88% and a PPV of 100%. Of the 48 patients with both negative preoperative CT and PET scans, only 1 (2.1%) had metastatic nodal disease, and this was suspected based on the clinical assessment. Of the patients with negative CT and PET scans and a negative clinical assessment (n = 39), none had involved perihepatic nodes. CONCLUSIONS: In patients with 1(o) and metastatic liver cancer, the incidence of truly occult metastatic disease to perihepatic lymph nodes is low. Routine sampling of perihepatic lymph nodes will therefore have a low yield in patients without some evidence of disease on preoperative CT or PET scans or at the time of exploration.

Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperative chemoradiation: a means for determining longterm outcomes of rectal cancer.

BACKGROUND: We have previously demonstrated that fluorodeoxyglucose-positron emission tomography (FDG-PET) can assess extent of pathologic response of primary rectal cancer to preoperative chemoradiation. Our goal was to determine the prognostic significance of FDG-PET assessment of rectal cancer response to preoperative chemoradiation. STUDY DESIGN: Fifteen patients with locally advanced primary rectal cancer (clinically bulky or tethered, or ultrasound evidence of T3-4 disease, N1 disease, or both) deemed eligible for preoperative radiation and 5-FU-based chemotherapy (5,040 cGy to the pelvis and 2 cycles of bolus 5-FU/leucovorin) were prospectively enrolled from May 1997 to September 1998. FDG-PET was performed before and 4 to 5 weeks after completion of preoperative chemoradiation. FDG-PET parameters included maximum standard uptake value (SUV(max)), total lesion glycolysis (TLG), and visual response score. Patients were prospectively followed after operation, and disease status was determined. RESULTS: All patients demonstrated some degree of response to preoperative therapy based on pathologic examination. At a median followup of 42 months (range 23 to 54 months), 11 patients had no evidence of disease and 4 had died of disease. The mean percentage decrease in SUV(max) (DeltaSUV(max)) was 69% for patients free from recurrence and 37% for patients with recurrence (p = 0.004). DeltaSUV(max) >or= 62.5 and deltaTLG >or= 69.5 were the best predictors of no-evidence-of-disease status and freedom from recurrence. Patients with DeltaSUV(max) >or= 62.5 and deltaTLG >or= 69.5 had significantly improved disease-specific and recurrence-free survival (p = 0.08, 0.02 and p = 0.03, 0.01, respectively). CONCLUSIONS: Our results indicate that FDG-PET assessment of locally-advanced rectal cancer response to preoperative chemoradiation may predict longterm outcomes.