Verbeke CS. Resection margins and R1 rates in pancreatic cancer—are we there yet

Department of Histopathology, St James's University Hospital, Leeds, UK.
Histopathology (Impact Factor: 3.45). 07/2008; 52(7):787-96. DOI: 10.1111/j.1365-2559.2007.02935.x
Source: PubMed


The prognosis of pancreatic cancer is poor, even for those patients who undergo surgical resection. The rate of local recurrence is high, despite the fact that in most series complete ('R0') resection is reported to be achieved in the majority of patients. The discrepancy between pathological assessment and clinical outcome indicates that microscopic margin involvement (R1) is frequently underreported, and potential causes for this are discussed in this review. Special emphasis is given to the variation that exists between currently used dissection techniques and their impact on the assessment of the resection margins in pancreatoduodenectomy specimens.

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    • "Pathology guidelines that change the incidence of histopathology parameters are clinically relevant since the parameters carry prognostic information. Guidelines on gross examination and sectioning of pancreaticoduodenectomy (PD) specimens have changed during the last years, after the introduction of the Leeds pathology protocol (LEEPP) [1]. This standardized procedure raised the incidence of involved margins (R1) and involved lymph nodes (N1), and also decreased pancreatic origin and increased distal bile duct origin [2,3] compared to large series using non-standardized procedures [4-10]. "
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    ABSTRACT: Variability in reported histopathology parameters in operated periampullary adenocarcinomas may affect the prognostic weight of the parameters. Standardized axial sectioning produces a higher incidence of involved margins and also seems to produce a lower relative incidence of pancreatic compared with distal bile duct origin and a higher incidence of involved lymph nodes, compared with non-standardized procedure. The aims of this study were to 1) assess how a previously not described standardized pathology procedure, with longitudinal sectioning along the distal bile duct, affects reported tumour origin, margin status and involved lymph nodes, compared with non-standardized procedure, 2) assess if re-evaluation of microscopic slides affects the prognostic value of margin status and 3) compare the results of this standardized procedure with reported results of other standardized and non-standardized procedures. One hundred seventy-five consecutive pancreaticoduodenectomy specimens with primary adenocarcinomas, operated during 2001 - 2011 at the University hospitals of Lund and Malmo, Sweden, were re-evaluated histologically, and parameters relevant for classification and prognosis were assessed, with 1 mm as a threshold for involved or uninvolved margins. Follow-up lasted until 31 December 2013. Five-year overall survival (OS) and hazard ratios (HR) were calculated for the margin status stated in the original reports and margin status after re-evaluation. Compared with non-standardized cases (n = 129), standardized cases (n = 46) had more involved lymph nodes in the specimens (median 3 vs 1), a higher fraction of distal bile duct origin (39% vs 21%) and a higher fraction of involved margins (74% vs 47%). The prognostic value of uninvolved margins increased by re-evaluation of slides (p < 0.001) and the adjusted HR for involved margins increased from 1.6 (95% CI 1.1 - 2.4) to 3.3 (95% CI 1.5 - 7.0). Uninvolved margins remained a significant predictor of OS in adjusted analysis. Both the method of sectioning the specimen and the microscopic assessment affect prognostic pathology parameters significantly. The results of the herein described standardized method are similar to the results of other standardized procedures. The 1-mm threshold for involved margins in pancreaticoduodenectomies is relevant for OS, and margin status is an independent prognostic parameter.Virtual slides: The virtual slides for this article can be found here:
    Full-text · Article · Apr 2014 · Diagnostic Pathology
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    • "Most studies show that R1 resection results in a poor survival rate, although some studies have failed to show R1 resection as an independent prognostic factor for long-term survival (Neoptolemos et al. 2004, 2010; Chang et al. 2009; Fatima et al. 2010; Edge et al. 2010; Raut et al. 2007; Winter et al. 2006). In our cohort, 58.2% had a R1 resection, which is above the reported average of 30–40% in the literature, although the quoted rates vary widely from 16 to 85% (Verbeke 2008). However, all patients without T4 or metastatic disease were considered for resection by us, as this oVers the best longterm outcome. "
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    ABSTRACT: Loco (regional)-recurrence rate after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) remains high, and the efficiency of adjuvant chemoradiotherapy is still debated. We aimed to assess predictors of loco-recurrence in order to tailor the indications for adjuvant chemoradiotherapy. Patients who underwent PD for PDAC between January 2001 and December 2010 were retrieved from a prospective database. Tumor recurrence was categorized as either loco-recurrence or distant recurrence. Clinicopathological characteristics and survivals were compared between patients with different recurrence patterns. The predictors for loco-recurrence were assessed. Seventy-nine patients were included. Loco-recurrence alone was identified in 22 patients (27.8%), distant recurrence alone in 33 (41.8%), both loco- and distant recurrences in 17 (21.5%) and no recurrence in 7 (8.9%). Median survival after recurrence (SAR) was significantly better in patients with loco-recurrence alone than in those with distant recurrence alone (10.4 vs. 5.0 months, P = 0.002) or in those with both loco- and distant recurrences (10.4 vs. 5.8 months, P = 0.044); the survival for patients with distant recurrence alone and those with both patterns was identical. Patients with early recurrence had a significantly poorer SAR than those with late recurrence (median, 5.5 vs. 9.0 months, P = 0.001). Logistic regression analysis revealed that positive resection margin (P = 0.001, HR = 14.532; 95% CI 7.399-38.466), early T stage (P = 0.018, HR = 0.014; 95% CI 0.000-0.475) and large tumor size (P = 0.030, HR = 4.345; 95% CI 1.152-16.391) were the determinant factors directly related to loco-recurrence alone. Patients with PDAC loco-recurrence alone had a significantly better SAR than those with distant recurrence. Adjuvant chemoradiotherapy should be considered to reduce loco-recurrence further and improve long-term survival.
    Full-text · Article · Mar 2012 · Journal of Cancer Research and Clinical Oncology
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    • "The lack of consensus regarding definition of the relevant margins and the absence of a standardized nomenclature are recognized problems in pathological reporting for pancreatic resections with PDAC [13]. "
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    ABSTRACT: To date, curative resection is the only chance for cure for patients suffering from pancreatic ductal adenoacarcinoma (PDAC). Despite low reported rates of microscopic tumor infiltration (R1) in most studies, tumor recurrence is a common finding in patients with PDAC and contributes to extremely low long-term survival rates. Lack of international definition of resection margins and of standardized protocols for pathological examination lead to high variation in reported R1 rates. Here we review recent studies supporting the hypothesis that R1 rates are highly underestimated in certain studies and that a microscopic tumor clearance of at least 1 mm is required to confirm radicality and to serve as a reliable prognostic and predictive factor.
    Full-text · Article · Dec 2010 · Cancers
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