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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    • "The resection rate depends upon the preoperative radiologic workup with high quality CT scan, MRI and/or laparoscopy, and is reported as 60 % without and 82 % with lapar- oscopy [15]. The R0 resection rate varies from 25– 84 % and depends upon the dissection technique and pathological workup [16]. In the 2014 Dutch National Audit 33 % of patients appeared to have an irresectable tumour at explorative laparotomy after radiologic assessment [17]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2–7 % and has hardly improved over the last two decades. Approximately 15 % of all patients have resectable disease at diagnosis, and of those, only a subgroup has a resectable tumour at surgical exploration. Data from cohort studies have suggested that outcome can be improved by preoperative radiochemotherapy, but data from well-designed randomized studies are lacking. Our PREOPANC phase III trial aims to test the hypothesis that median overall survival of patients with resectable or borderline resectable pancreatic cancer can be improved with preoperative radiochemotherapy. Methods/design The PREOPANC trial is a randomized, controlled, multicentric superiority trial, initiated by the Dutch Pancreatic Cancer Group. Patients with (borderline) resectable pancreatic cancer are randomized to A: direct explorative laparotomy or B: after negative diagnostic laparoscopy, preoperative radiochemotherapy, followed by explorative laparotomy. A hypofractionated radiation scheme of 15 fractions of 2.4 gray (Gy) is combined with a course of gemcitabine, 1,000 mg/m2/dose on days 1, 8 and 15, preceded and followed by a modified course of gemcitabine. The target volumes of radiation are delineated on a 4D CT scan, where at least 95 % of the prescribed dose of 36 Gy in 15 fractions should cover 98 % of the planning target volume. Standard adjuvant chemotherapy is administered in both treatment arms after resection (six cycles in arm A and four in arm B). In total, 244 patients will be randomized in 17 hospitals in the Netherlands. The primary endpoint is overall survival by intention to treat. Secondary endpoints are (R0) resection rate, disease-free survival, time to locoregional recurrence or distant metastases and perioperative complications. Secondary endpoints for the experimental arm are toxicity and radiologic and pathologic response. Discussion The PREOPANC trial is designed to investigate whether preoperative radiochemotherapy improves overall survival by means of increased (R0) resection rates in patients with resectable or borderline resectable pancreatic cancer. Trial registration Trial open for accrual: 3 April 2013 The Netherlands National Trial Register – NTR3709 (8 November 2012) EU Clinical Trials Register – 2012-003181-40 (11 December 2012)
    Full-text · Article · Dec 2016 · Trials
    • "Since R0 resection is probably one of the most important prognostic factors for patient outcome [18], achieving this is the main goal of pancreatic surgery. In reality, the proportion of R1 resections (<1 mm margin), as analysed by standardised pathology laboratory analysis, exceeds 75%, even in experienced centres [19,20]. To achieve R0 resection, some authors have proposed systematic PV resection during PD [21], however, no strong data yet exist to support this actually promoting R0 resection and, more importantly, improving disease-free survival (DFS) or overall survival (OS). "
    [Show abstract] [Hide abstract] ABSTRACT: Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.
    No preview · Article · Apr 2016 · European journal of cancer (Oxford, England: 1990)
    • "The present series is consistent with this evidence reporting 3 and 5-year survival rates of 40 and 18 %, respectively. We reported a R0 resection rate of 73.9 %, but as reported in other studies [8, 9], it has been probably overestimated if we consider only 18 % of a 5-year survival rate. Data on patterns of disease recurrence were available only for 12 patients who underwent radical R0 resection: 11 patients recurred with distant metastasis; only one of them developed local recurrence. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose Prognostic indicators for distal cholangiocarcinoma have not been widely confirmed because of its rarity. Despite the early appearance of symptoms, it has a very poor prognosis. The aim of this study was to identify prognostic factors in patients undergoing pancreaticoduodenectomy (PD) for distal bile duct cancer (DBDC) in a high-volume center for pancreatic disease. Methods From January 2000 to December 2013, 1490 PD were performed for periampullary disease. Data from all patients with histologically proven cholangiocarcinoma were reviewed. Preoperative data, post-operative complications, pathologic features, and survival were investigated. Results Among 50 histologically proven DBDC (3.3 %), 4 patients who underwent CBD resection were excluded. Thus, the study population consisted of 46 patients. Overall surgical morbidity rate was 67.4 %; mortality was nil. Major complications were pancreatic fistula (47.8 %), abdominal collections (34.8 %), post-pancreatectomy hemorrhage (21.7 %), and delayed gastric emptying (10.9 %). The majority of resections were R0 (73.9 %). The presence of metastatic lymph nodes (N1) was identified in 76.1 % of cases. Among N1 cases, the most frequently involved lymph nodes were pancreaticoduodenal nodes (50 %), hepatoduodenal ligament nodes (21.7 %), superior mesenteric artery nodes (8.7 %), and anterior hepatic artery nodes (4.3 %). Overall, survival rates were 88.8, 40, and 18 % at 1, 3, and 5 years, respectively. Median survival was 31 months. By univariate analysis, only tumor grading and nodal metastasis were predictors of poor prognosis (p
    No preview · Article · Jul 2015 · Langenbeck s Archives of Surgery
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