новая папка / Operative Standards for Cancer Surgery Volume I 1st Edition

24.Meszoely IM, Lee JS, Watson JC, et al. Peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreas. Am Surg 2004;70(3):208-213; discussion 213-214.

25.Bilimoria KY, Bentrem DJ, Lillemoe KD, et al. Assessment of pancreatic cancer care in the United States based on formally developed quality indicators. J Natl Cancer Inst 2009;101(12):848-859.

26.Sabater L, García-Granero A, Escrig-Sos J, et al. Outcome quality standards in pancreatic oncologic surgery. Ann Surg Oncol

2014;21:1138-1146.

27.Tseng JF, Pisters PW, Lee JE, et al. The learning curve in pancreatic surgery. Surgery 2007;141(5):694-701.

28.Gillen S, Schuster T, Meyer zum Büschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010;7(4):e1000267.

29.Neoptolemos JP, Stocken DD, Dunn JA, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg 2001;234(6):758-

30.Raut CP, Tseng JF, Sun CC, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg 2007;246(1):52-60.

31.Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000;4(6):567-579.

32.Butturini G, Stocken DD, Wente MN, et al. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg 2008;143(1):75-83; discussion 83.

33.Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27(11):1806-1813.

34.Verbeke CS, Leitch D, Menon KV, et al. Redefining the R1 resection in pancreatic cancer. Br J Surg 2006;93(10):1232-1237.

35.Katz MH, Merchant NB, Brower S, et al. Standardization of surgical and pathologic variables is needed in multicenter trials of adjuvant therapy for pancreatic cancer: results from the ACOSOG Z5031 trial. Ann Surg Oncol 2011;18(2):337-344.

36.Exocrine and endocrine pancreas. In: Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:241-249.

37.Washington K, Berlin J, Branton P, et al. Protocol for the examination of specimens from patients with carcinoma of the exocrine pancreas. 2011. http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasExo_11protocol.pdf. Accessed February 6, 2015.

38.Verbeke CS, Menon KV. Redefining resection margin status in pancreatic cancer. HPB (Oxford) 2009;11(4):282-289.

39.Campbell F, Foulis AK, Verbeke CS. Dataset for the histopathological reporting of carcinomas of the pancreas, ampulla of Vater and common bile duct. 2010. http://www.rcpath.org/Resources/RCPath/Migrated%20Resources/Documents/D/datasethistopathologicalreportingcarcinomas may10.pdf.

40.Delpero JR, Bachellier P, Regenet N, et al. Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens. HPB (Oxford) 2014;16(1):20-33.

41.Adsay NV, Basturk O, Saka B, et al. Whipple made simple for surgical pathologists: orientation, dissection, and sampling of pancreaticoduodenectomy specimens for a more practical and accurate evaluation of pancreatic, distal common bile duct, and

ampullary tumors. Am J Surg Pathol 2014;38(4):480-493.

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Pancreatic Surgery: Key Question

Among patients who have resectable pancreatic adenocarcinoma with venous or arterial involvement, does performing a pancreatectomy with vascular resection and reconstruction result in better survival outcomes than performing an R2 resection or aborting surgery?

INTRODUCTION

First described in 19511 and later conceptualized as an “extended Whipple procedure,”2,3 vascular resection and reconstruction (VR) at pancreatectomy for cancer has been an area of considerable interest. Authors of singleand multiple-institution reports and of large database analyses have described a significant experience with pancreatectomy with and without resection of the portal vein, superior mesenteric vein, hepatic artery, and occasionally superior mesenteric artery. Despite these studies, the extent to which VR at pancreatectomy improves survival outcomes in patients who have resectable pancreatic adenocarcinoma with venous or arterial involvement remains unknown. The current review seeks to answer the following question, to the extent that the data can be extracted from the literature and compared: Among patients who have resectable pancreatic adenocarcinoma with venous or arterial involvement, does performing a pancreatectomy VR/reconstruction result in better survival outcomes than performing an R2 resection or aborting surgery?

For clarity and comparability, we have focused on survival as the oncologic metric of interest. Other important metrics include margin status, perioperative morbidity, and the ability to receive adjuvant therapy, insofar as they are associated with overall survival. Although they are beyond the scope of the review, performance status and quality of life, which are increasingly studied outcome measures, may also add additional insight to future investigations and are particularly important in the design of clinical trials. Other issues that are related to the care of patients undergoing planned pancreatectomy, such as whether adjuvant treatments should be given before or after surgery, are beyond the scope of this review but are important considerations when determining whether patients with pancreatic adenocarcinoma with apparent vascular involvement are candidates for pancreatectomy.

METHODOLOGY

Two authors independently performed an organized search of PubMed for English language articles with abstracts published from January 1990 through March 2014. Keyword combinations included “vascular resection” plus “pancreatectomy”; “vascular resection” plus “pancreatic cancer”; (“margin status” or “positive margin” or “R1” or “R2”) plus “pancreatic cancer” plus “survival”; and (“locally unresectable” or “borderline”) plus “pancreatic cancer” plus “survival.”

P.199 The initial search yielded 1,045 unique articles. Of these articles, 849 review articles, duplicate series, and technique-focused papers were excluded based on a review of the title and brief review of the abstract because they did not meet the inclusion criteria. The remaining 196 abstracts were reviewed in detail by both authors independently, and an additional 164 abstracts were excluded because the study did not address the clinical question of interest. Thus, both investigators reviewed 32 full-text articles independently. Of these 32 articles, 16 were excluded because they were small series, had inadequate survival data, had no data for patients who did or did not undergo VR at pancreatectomy, or had inadequate follow-up; the final 16 articles were then selected that were used for the complete

review of the data (Fig. 13-4).4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 Each article was

P.200 then reviewed by both authors and assigned a strength of recommendation based on the Grades of Recommendation, Assessment,

Development, and Evaluation system.20

FIGURE 13-4 CONSORT diagram.

FINDINGS

The reviewed papers are listed in Table 13-1. No randomized studies have compared survival outcomes in patients with vascular involvement by tumor following pancreatectomy with and without VR. Most of the reviewed articles are retrospective reports describing one institution’s experience with pancreatectomy with VR over time; some of these articles include comparison groups of patients who underwent non-VR pancreatectomies. A few studies compared the outcomes of patients who underwent VR with those of patients in whom surgery was aborted or patients who received palliative surgery. Because no papers specifically compared survival data for the three pancreatectomy groups of interest—patients who underwent VR, patients who underwent R2 resection, and patients in whom surgery was aborted—some relatively high-quality studies that analyzed the survival outcomes of one or two of these three groups were included in the review for the purpose of comparison.

Survival Following Pancreatectomy with VR versus that Following Pancreatectomy without VR

The overall theme of the larger, more recent series is the comparison of outcomes of pancreatic adenocarcinoma patients who undergo VR at pancreatectomy with those who do not undergo VR at such operations. Although there is some patient heterogeneity in these series, they tend to advance the concept that, compared with patients who do not undergo VR, those who do undergo VR potentially

have more morbidity and have survival outcomes that are moderately worse,9,13 or similar,15 after multivariable adjustment.5,8 In the fulltext articles, the median survival time after pancreatectomy with portal vein/superior mesenteric vein VR for pancreatic adenocarcinoma

ranges from 10 to 23 months.4,5,6,7,8,9,10,11,13,14,15,18 Analyses of outcomes following arterial resections were limited by small sample sizes but suggested that the outcomes of patients who undergo arterial resection at pancreatectomy are worse than those of patients

who undergo portal vein/superior mesenteric vein resection only at the time of surgery.4,10

Survival Following Pancreatectomy with VR versus that Following R2 Resection

In determining resectability, whether before or during surgery, surgical oncologists must weigh the value of performing a VR to obtain negative or at least grossly negative (R0/R1) margins against that of not performing VR and instead obtaining a grossly positive

margin.21 One difficulty in directly comparing the evidence for these two approaches is the rarity with which R2 margins are identified and survival data for R2 resection patients are reported in the literature. In fact, some studies have deliberately excluded R2 patients from

their analyses of survival data.14 In addition, in studies using larger or older data sets, patients considered to have undergone an R1 resection may include patients whose surgery, given either additional surgeon input in the form

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of a more oncologically detailed operative note or consistent pathologic methods, would be designated an R2 resection.

TABLE 13-1 Studies Assessing Overall Survival of Pancreatic Adenocarcinoma Patients Technically Undergoing Pancreatectomy with or without Vascular Resection

DA, decision analysis; DFS, disease free survival; HA, hepatic artery; HR, hazard ratio; IVC, inferior vena cava; KM, Kaplan Meyer; NCDB, National Cancer Database; OS, overall survival; PDAC, pancreatic cancer; PD, pancreatoduodenectomy; PV/SMV, portal vein/superior mesenteric vein; VR, vascular resection.

Using the National Cancer Database, composed of patient data from Commission on Cancer-accredited hospitals, Bilimoria et al17 stratified patient survival according to surgical margin status. The median overall survival durations of patients who underwent R0, R1, or R2 pancreatectomies were 16.7 months, 12.3 months, and 7.1 months, respectively. Although the study was limited by its use of administrative data, its findings suggest that the survival outcomes of patients who undergo margin-negative resections and those who

undergo margin-positive resections differ substantially. Fatima et al,16 from the Mayo Clinic, also assessed patients’ survival according to their margin status following resection. Patients with R0 resections had a median survival duration of 18 to 19 months, depending on whether en bloc resection was performed; patients with R1 resections had a median survival duration of 15 months; and patients with R2 resections had a median survival duration of 10 months. Although the Mayo Clinic study included 99 patients who underwent pancreatectomy with VR, it did not directly compare the survival outcomes of patients who underwent pancreatectomy with VR to those who underwent an R2 resection. The hazard ratio for death was significant for patients with R2 resection (HR = 2.15, P = .002) but not

those with R1 resection (HR = 1.26, P = .08). Finally, Konstantinidis et al12 published the Massachusetts General Hospital experience, in which patients who had “wide” R0 surgical margins (>1 mm) had a median survival duration of 35 months, whereas patients who had “close” R0 surgical margins (≤1 mm) had a median survival duration of 16 months, which was similar to that of patients who underwent R1 resection (14 months).

Survival Following Pancreatectomy with VR versus that Following Aborted Surgery

Data from studies directly comparing outcomes following pancreatectomy with PD with those following aborted or palliative procedures are analogously limited. However, data from an article detailing the Massachusetts General Hospital experience with VR suggest that patients with locally advanced disease who undergo palliative surgery or in whom surgery is aborted have a median survival duration of

11 months.12 One recent multicenter series from the United Kingdom demonstrated that patients who did or did not undergo VR had similar median survival times (18.2 months and 18 months, respectively); in both groups, >50% of patients had R1 margins. In contrast,

surgical bypass patients had a median survival duration of 8 months.8

CONCLUSION

Published data are generally from high-volume centers and may not be generalizable to smaller centers. This limitation notwithstanding, available data suggest that patients who undergo pancreatectomy with VR have a longer overall survival time than those undergoing R2 resections or aborted operations. The data for venous reconstructions are more robust than those for arterial reconstructions. Accurate preoperative staging using high quality imaging, and judicious use of preoperative therapies to select those patients most likely benefit from these aggressive operations, are both critical.

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