Dilemmas for the pathologist in the oncologic assessment of pancreatoduodenectomy specimens

A pancreatoduodenectomy specimen is complex, and there is much debate on how it is best approached by the pathologist. In this review, we provide an overview of topics relevant for current clinical practice in terms of gross dissection, and macro- and microscopic assessment of the pancreatoduodenectomy specimen with a suspicion of suspected pancreatic cancer. Tumor origin, tumor size, degree of differentiation, lymph node status, and resection margin status are universally accepted as prognostic for survival. However, different guidelines diverge on important issues, such as the diagnostic criteria for evaluating the completeness of resection. The macroscopic assessment of the site of origin in periampullary tumors and cystic lesions is influenced by the grossing method. Bi-sectioning of the head of the pancreas may offer an advantage in this respect, as this method allows for optimal visualization of the periampullary area. However, a head-to-head comparison of the assessment of clinically relevant parameters, using axial slicing versus bi-sectioning, is not available yet and the gold standard to compare both techniques prospectively might be subject of debate. Further studies are required to validate the various dissection protocols used for pancreatoduodenectomy specimens and their specific value in the assessment of pathological parameters relevant for prognosis

Axial slicing versus bivalving in the pathological examination of pancreatoduodenectomy specimens (APOLLO): a multicentre randomized controlled trial

Background: In pancreatoduodenectomy specimens, dissection method may affect the assessment of primary tumour origin (i.e. pancreatic, distal bile duct or ampullary adenocarcinoma), which is primarily determined macroscopically. This is the first study to prospectively compare the two commonly used techniques, i.e. axial slicing and bivalving. Methods: In four centres, a randomized controlled trial was performed in specimens of patients with a suspected (pre)malignant tumour in the pancreatic head. Primary outcome measure was the level of certainty (scale 0–100) regarding tumour origin by four independent gastrointestinal pathologists based on macroscopic assessment. Secondary outcomes were inter-observer agreement and R1 rate. Results: In total, 128 pancreatoduodenectomy specimens were randomized. The level of certainty in determining the primary tumour origin did not differ between axial slicing and bivalving (mean score 72 [sd 13] vs. 68 [sd 16], p = 0.21), nor did inter-observer agreement, both being moderate (kappa 0.45 vs. 0.47). In pancreatic cancer specimens, R1 rate (60% vs. 55%, p = 0.71) and the number of harvested lymph nodes (median 16 vs. 17, p = 0.58) were similar. Conclusion: This study demonstrated no differences in determining the tumour origin between axial slicing and bivalving. Both techniques performed similarly regarding inter-observer agreement, R1 rate, and lymph node harvest

Optical diagnosis expanded to small polyps: Post-hoc analysis of diagnostic performance in a prospective multicenter study

Background: Optical diagnosis can replace histopathology of diminutive (1-5mm) polyps if surveillance intervals based on optical diagnosis of polyps have≥90% agreement with intervals based on polyp histology and if the negative predictive value (NPV) for predicting neoplastic histology in the rectosigmoid is≥90%. This study aims to assess whether small (6-9mm) polyps can be included in optical diagnosis strategies. Method: This is a post-hoc analysis of a prospective multicenter study in which 27 endoscopists, all performing endoscopies for the Dutch screening program, were trained in optical diagnosis. For 1 year, endoscopists recorded the predicted histology for all lesions detected using narrow-band imaging during 3144 consecutive colonoscopies after a positive fecal immunochemical test, along with confidence levels. Surveillance interval agreement and NPV were calculated for high confidence predictions for polyps of 1-9mm and compared with histopathology. Surveillance interval agreement was calculated using the European Society of Gastrointestinal Endoscopy surveillance guideline. Results: Surveillance interval agreement was 95.4% (confidence interval [CI] 94.2%-96.4%), and NPV for predicting neoplastic histology in the rectosigmoid 90.0% (CI 87.3%-92.2%). The reduction in histology (45.9% vs. 30.5%) and the proportion of patients who could have received direct surveillance advice (15.6% vs. 7.3%) was higher when small polyps were included (P <0.001). T1 cancer was found in seven small polyps (0.33%), five of which would have been discarded without histopathology. Conclusion: Including small polyps in the optical diagnosis strategy improves its efficacy while maintaining performance thresholds. However, there is a small risk of missing T1 cancers when small polyps are included in the optical diagnosis strategy

Optical Diagnosis of Sessile Serrated Polyps: Bottleneck for the Optical Diagnosis Paradigm?

Optical diagnosis of diminutive (1 to 5 mm) polyps could result in a more cost-effective colonoscopy practice. Previous optical diagnosis studies did not incorporate the differentiation of sessile serrated polyps (SSPs). This study aimed to evaluate the impact of optical diagnosis of diminutive SSPs on the overall performance of endoscopic polyp differentiation in daily colonoscopy practice. Endoscopy data were prospectively collected between 2011 and 2014 in a colonoscopy center. Each endoscopist reported a real-time optical diagnosis (SSP, adenoma or hyperplastic polyp) for all lesions in a structured colonoscopy reporting system, using narrow band imaging at their discretion. Study outcomes were accuracy of optical diagnosis, surveillance interval agreement and negative predictive value for diminutive rectosigmoid neoplastic histology based on the optical diagnosis of diminutive polyps compared to histopathology. Of 2853 removed diminutive polyps, 202 (7.1%) were histologically proven SSPs. Optical diagnosis of diminutive SSPs was accurate in 24.4%. Diminutive SSPs determined 6.9% of postpolypectomy surveillance assignments. Inaccurate optical diagnosis of diminutive SSPs led to lower surveillance interval agreement (78.1% vs. 53.3%, P <0.01) and pooled negative predictive value per polyp (84.3% vs. 50.0%; P <0.01) in patients with diminutive SSPs when compared to patients without diminutive SSPs. Accurate endoscopic identification of diminutive SSPs improved from 0% in 2011 to 47% in 2014 (P=0.02). Endoscopic characterization of diminutive SSPs is difficult, impairing overall performance of optical diagnosis in patients with diminutive SSPs. Future optical diagnosis studies should use validated trainings and classification algorithms that include differentiation of SSP

Routine histopathologic examination of the appendix after appendectomy for presumed appendicitis: Is it really necessary? A systematic review and meta-analysis

Background: Owing to substantial costs and increasing interest in the nonoperative management of appendicitis, the necessity of routine histopathologic examination of appendectomy specimens is being questioned. The aim of this study was to determine whether routine histopathologic examination after appendectomy for suspected appendicitis should still be performed. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies listing the histopathologic diagnoses after appendectomy for suspected appendicitis. Main outcomes were the incidence of histopathologically proven aberrant findings, the ability of surgeons to recognize unexpected appendiceal pathology intraoperatively, and the percentage of aberrant findings resulting in a change of postoperative management. A meta-analysis was performed using a random-effects model. Results: Twenty-five studies with 57,357 patients were included. The pooled percentage of aberrant findings was 2.52% (95% confidence interval 1.81–3.51). Neoplasms were found in 0.71% (95% confidence interval 0.54–0.94). Findings of the intraoperative assessment by the surgeon were reported for 82 of the 2,718 (3.0%) unexpected diagnoses, with great variation between studies. The impact on postoperative management was described for 237 of 2,718 (8.7%) aberrant findings. Of these, 166 (70.0%) resulted in a change of postoperative management. Conclusion: Based on current evidence, it remains unclear how many of the unexpected appendiceal pathologies with clinical consequences can be identified intraoperatively by the surgeon. Until reliable data on the safety and potential cost savings of a selective policy becomes available, we advise sending appendectomy specimens routinely for histopathologic examination

Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable to an age- and gender-matched control population: case-control study with expert pathology review

Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) due to microsatellite instability. The role of sessile serrated lesions (SSLs) and the serrated neoplasia pathway in these patients is unknown. The aim of this matched case-control study was to compare endoscopic detection rates and distribution of SSLs in Lynch syndrome patients to a matched control population. We collected data of Lynch syndrome patients with a proven germline mutation who underwent colonoscopy between January 2011 and April 2016 in 2 tertiary referral hospitals. Controls undergoing elective colonoscopy from 2011 and onward for symptoms or surveillance were selected from a prospectively collected database. Patients were matched 1:1 for age, gender, and index versus surveillance colonoscopy. An expert pathology review of serrated polyps was performed. The primary outcomes included the detection rates and distribution of SSLs. We identified 321 patients with Lynch syndrome who underwent at least one colonoscopy. Of these, 223 Lynch patients (mean age 49.3, female 59%, index colonoscopy 56%) were matched to 223 controls. SSLs were detected in 7.6% (CI, 4.8-11.9) of colonoscopies performed in Lynch patients and in 6.7% (CI, 4.1-10.8) of controls (p = 0.86). None of the detected SSLs in Lynch patients contained dysplasia. The detection rate of SSLs in Lynch patients undergoing colonoscopy is comparable to a matched population. These findings suggest that the role of the serrated neoplasia pathway in CRC development in Lynch syndrome seems to be comparable to that in the general populatio

Optimising diagnostics to discriminate complicated from uncomplicated appendicitis: a prospective cohort study protocol

INTRODUCTION: Growing evidence is showing that complicated and uncomplicated appendicitis are two different entities that may be treated differently. A correct diagnosis of the type of appendicitis is therefore essential. The Scoring system of Appendicitis Severity (SAS) combines clinical, laboratory and imaging findings. The SAS rules out complicated appendicitis in 95% (negative predictive value, NPV) and detects 95% (sensitivity) of patients with complicated appendicitis in adults suspected of acute appendicitis. However, this scoring system has not yet been validated externally. In this study, we aim to provide a prospective external validation of the SAS in a new cohort of patients with clinical suspicion of appendicitis. We will optimise the score when necessary. METHODS AND ANALYSIS: The SAS will be validated in 795 consecutive adult patients diagnosed with acute appendicitis confirmed by imaging. Data will be collected prospectively in multiple centres. The predicted diagnosis based on the SAS score will be compared with the combined surgical and histological diagnosis. Diagnostic accuracy for ruling out complicated appendicitis will be calculated. If the SAS does not reach a sensitivity and NPV of 95% in its present form, the score will be optimised. After optimisation, a second external validation will be performed in a new group of 328 patients. Furthermore, the diagnostic accuracy of the clinical perspective of the treating physician for differentiation between uncomplicated and complicated appendicitis and the patient's preferences for different treatment options will be assessed. ETHICS AND DISSEMINATION: Ethical approval was granted by the Amsterdam UMC Medical Ethics Committee (reference W19_416 # 19.483). Because of the observational nature of this study, the study does not fall under the scope of the Medical Research Involving Human Subjects Act. Results will be presented in peer-reviewed journals. This protocol is submitted for publication before analysis of the results

The density of CD8+ T-cell infiltration and expression of BCL2 predicts outcome of primary diffuse large B-cell lymphoma of bone

HP