chapter 3 lymphadenectomy in pancreatic cancer surgery · recent advances in pancreatic cancer...

2 www.avidscience.com

Recent Advances in Pancreatic Cancer

Chapter 3

Lymphadenectomy in Pancreatic Cancer SurgeryDaniel Kostov

Department of Surgery, Naval Hospital of Varna, Bulgaria

*Corresponding Author: Daniel Kostov, Department of Surgery, Naval Hospital of Varna, Bulgaria, Email: [email protected]

First Published March 23, 2016

Copyright: © 2016 Daniel Kostov

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source.

3


www.avidscience.com

AbstractPancreatic cancer is one of the most aggressive malig-

nancies with poor rates of survival. Lymph node involve-ment in pancreatic adenocarcinoma is a key prognostic factor. We present the operative technic and the volume of the standard lymph node dissection, as well as our own experience with this type of operation. Pancreaticoduo-denectomy with standard lymphadenectomy including at least 15 lymph nodes should be the procedure of choice in adenocarcinoma of the pancreatic head. Extended lym-phadenectomy should not be applied routinely in patients with pancreatic cancer requiring pancreaticoduodenec-tomy or distal pancreatectomy. The radical antegrade modular pancreato-splenectomy is recommended for cancer location in the body or tail. Lymph node ratio ≥ 0.2 is an independent adverse prognostic factor, which is powerful and useful for prognostic assessment for pancre-atic cancer. We establish a directly proportional correla-tion between the presence of metastatic lymph nodes in-dependently of their number and the development of local recurrence and distant metastases. The most commonly affected by metastasis are lymph nodes around superior mesenteric artery (station 14) and anterior pancreatic nodes (station 13). Pancreatic cancer should be managed as a systemic disease, even in patients with evidence of only local or regional disease; consequently, any effort for local control can have little effect on survival. This finding confirms the fact that the biology of the disease remains the most important determining factor affecting the final



outcome, despite the progress in surgical technique and systemic therapy.

IntroductionPancreatic cancer (PC) treatment is an interdiscipli-

nary challenge as this tumor entity is still characterized by a poor prognosis, with long-term survival less than 6% [1-3]. PC causes about 20 million deaths worldwide each year with an increasing incidence rate [4]. Nowadays it is the fourth leading cause of death among cancers, and is one of the common gastrointestinal malignancies. Although recent advances in chemotherapy have made an impact on PC treatment, the surgical resection still remains the only hope for cure of this lethal disease [5,6]. However, the PC easily invades to adjacent organs, especially to the surrounding major vasculatures, due to its malignant be-havior and the anatomical location of the pancreas. Less than 20% of patients who present with PC have resectable tumors because of local invasion, together with frequent occurrences of distant metastasis[7]. The Cancer Statistics Review (2002–2008) from the US Surveillance Epidemi-ology and End Results showed that 53% of all patients with PC had concomitant distant metastases at the time of diagnosis; only 15–20% of the remaining patients were eligible for potentially curative resection, and up to 25% were staged as having locally advanced disease and thus were potentially ‘‘inoperable’’ because of involvement of

5


www.avidscience.com

surrounding major vessels [8].

Pancreatic resections for malignant disease processes, are some of the most technically challenging operations performed by surgeons. Difficulties with PC include the increased frequency of regional or distant lymph node involvement, positive resection margins in the pancreas itself and in the retroperitoneal tissues [9]. Despite the re-cent advances in imaging, staging, adjuvant therapy, ag-gressive surgery, and downstaging by neoadjuvant thera-py, there is no improvement in the overall survival of these patients. Randomized controlled trials of surgical resec-tion followed by adjuvant therapy demonstrate disease relapse rates of >70% [10] while autopsy series of patients after resection show local and distant failure rates of 75% and 88%, respectively [11]. Only 30%-40% of pancreatec-tomies achieve actual R0 resection, even in experienced hands, because of the early spread into and along the neu-ral sheaths [12].

Standardization of surgical procedures and centrali-zation of pancreatic surgery in high-volume institutions guarantees the best patient’s care, a mortality of 0,7%-3% and a morbidity of 36%-41% [13]. Median overall survival of primarily resectable patients ranges between 20 and 24 months, while survival in locally advanced, non-meta-static PC is 9-13 months only. However, in patients who are suitable for resection, five-year survival rates of 25% are possible, which underlines that surgery offers the only



chance of cure and long-term survival [14].

Pancreaticoduodenectomy (PD) is the only effective treatment for cancers of the pancreatic head region. The major goals that must be achieved during pancreatic re-section include reduced postoperative hemorrhaging and operation time, because integrated resection of the pan-creatic head is the most difficult step of radical PD in pa-tients with invasion or oppression of the portal vein and superior mesenteric vein by the tumor. The extent of the cancer to the regional lymph nodes is a powerful prognos-tic factor after resection independently from cancer histol-ogy [15]. For this reason, lymphadenectomy is considered a crucial step of PD for pancreatic head cancer. In 2014, a consensus meeting of the International Study Group on Pancreatic Surgery (ISGPS) in Verona on the definition and the prognostic role of lymphadenectomy during PD for cancer stated that: (i) the use of the nomenclature for nodal stations based on the classification of the Japanese Pancreas Society [21-16] is recommended; (ii) an extend-ed lymphadenectomy does not improve the oncological outcome of patients and should not be associated with PD for cancer; (iii) lymphadenectomy should include the re-moval of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (SMA) (14a right lateral side, 14b right lateral side) and nodes of the

7


www.avidscience.com

anterior surface of the pancreatic head (stations 17a and 17b) [17].

Whereas operable cancers of the pancreatic body and tail are less common than those of the pancreatic head, distal pancreatectomy (DP) is the only effective treat-ment for cancers of the pancreatic body and tail. DP has been the standard procedure for these cancers for dec-ades. However, the recurrence rate after DP has remained high [18-20]. Lymphadenectomy during pancreatectomy for patients with pancreatic adenocarcinoma in the body or tail includes nodes in stations 10 in the hilum of the spleen, 11 along the splenic artery, and 18 along the in-ferior border of the body and tail of the pancreas. Lymph node station 9 is only suggested to be included in the re-section when tumors are confined to the area of the body of the pancreas [17].

Today, standardization of surgical procedures and centralization of pancreatic surgery in high volume insti-tutions guarantees the bestpatient care and mortality rates below 5%. This chapter summarizes the current state of lymphadenectomy in surgery for pancreatic adenocarci-noma with focus on standard lymphadenectomy.Westud-iedthelymphnodeinvolvementinpatientswithresectableP-Cundergoing PD or DP with standard lymphadenectomy.



Standard LymphadenectomyLymphadenectomy in PancreaticoduodenectomyThe standard lymphadenectomy formulated by theIS-

GPS based on the literature and expert opinions is a guide for surgeons when operating on patients with resectable pancreatic adenocarcinoma. Compelling evidence-based reports, both randomized, controlled trials and meta-analyses, show no benefit to performing an extended lymphadenectomy [10,11,21-29]. Extended lymphad-enectomy has a harmful impact on patients undergoing oncological PD compared with standard lymphadenecto-my. A standard lymphadenectomy should include supra- and infrapyloric nodes (stations 5,6), nodes to the right of the hepatoduodenal ligament (stations 12b1, 12b2, and 12c), anterior and posterior pancreatico-duodenal nodes (stations 17a, 17b, 13a, and 13b), nodes to the right of the SMA ( stations 14a and 14b), and anterior to the common hepatic artery (station 8a) (Figure 1). Lymphnodestations 13 and 17 areembeddedwithinthepancreaticoduodenal-groove, andthereforearealwaysresectedwiththespecimen (Figure 2).

The standard lymphadenectomy includes lymph node stations 5, 6, 8a, 12b, and 12c found in the hepatoduode-nal ligament. Lymphadenectomy should extend up to the level of the right hepatic artery as it crosses over to the right liver to adequately clear the hepatoduodenal liga-

9


www.avidscience.com

ment (Figure 3 and Figure 4).

Figure 1: Volume of the standard lymphadenectomy dur-ing PD in patients with pancreatic head adenocarcinoma.



Figure 2: Lymph node stations 13 and 17 are embedded within the specimen– tumor (1), d. choledochus (2), duo-

denum (3).A complete resection of the lymph nodes around the

SMA as part of an extended lymphadenectomy has not been shown to be beneficial for the patient and leads to more morbidity, in particular postoperative diarrhea, and is not indicated. Diarrhoea, as assessed up to 4 months after surgery, was markedly more common in patients in whom nerve tissue surrounding the SMA was cleared cir-cumferentially. By contrast, in studies in which only the right lateral aspect of the nerve plexus was dissected, no impact on intestinal transit was observed. Only lymph node stations along the right side of the SMA (stations 14a and 14b) should be resected in a standard lymphadenec-tomy during PD (Figure 5, Figure 6 and Figure 7). Com-plete resection around the SMA is not indicated. Nodes around the celiac trunk should not be resected.

11


www.avidscience.com

Figure 3: Lymph node dissection in the hepatoduodenal-ligament: left gastric artery (1), proper hepatic artery (2), common hepatic artery (3), portal vein (4), interrupted commonhepatic duct (5) and an aberrant right hepatic ar-

tery (6) of Michels’ type III.Pawlik et al. demonstrated that less than 12 nodes re-

trieved in N0 disease resulted in poorer overall survival and Tomlinson and colleagues highlighted that ≧15 nodes were required to confer a survival advantage in N0 dis-ease [30,31]. The number of lymph nodes required to minimize the risk of the stage migration phenomenon is proposed to be between 10 and 15 [32,33]. The American Joint Committee on Cancer (AJCC) TNM classification and the Royal College of Pathologist of United Kingdom have set 12 and 15 lymph nodes, respectively, as the mini-mal number to be collected at surgery and these figures



were utilized to create categorical variables for the sur-vival analysis [34,35]. The standard lymphadenectomy should regularly provide ≧15 lymph nodes to ensure ad-equate pathologic staging of the disease [17].

Figure 4: Lymph node dissection in the hepatoduo-denal ligament: left gastric artery (1), left hepatic artery from which the artery for segment 4 (2) arises, common hepatic artery (3), portal vein (4), interrupted common hepatic duct (5), aberrant right hepatic artery of Michels’ type VIII (6), accessory left hepatic artery (7) and gas-

troduodenal artery (8).

13


www.avidscience.com

Figure 5: Lymphadenectomy along the right side of the SMA (2): mesenterico-portal vein (1) and an aberrant

right hepatic artery extending from the SMA (2).

The number of positive lymph nodes was shown to have an important impact on long-term outcome. In patients with one positive node, long-term survival was equal to patients with an N0 stage, whereas two or more positive nodes were associated with a significantly poorer survival, regardless to the total number of positive nodes. This observation was similarly made in DP with a cutoff level of three or more positive nodes. These results un-derline the importance of lymph node dissection, as in case of only one or two positive nodes the radical removal leads to a dramatically improved prognosis, compared to



patients with residual tumor manifestation or merely pal-liative therapy.

Figure 6: Lymphadenectomy along the right side of the SMA (3): portal vein (1), superior mesenteric vein (2) and an aberrant common hepatic artery extending from

the SMA (3).

Very important prognostic factor is the number of harvested lymph nodes and the ratio of positive to to-tal examined lymph nodes that is, the lymph node ratio. Lymph node ratio is a commonly used term initially in-troduced to characterize lymphatic tumor load and create a prognostic parameter independent from the rough esti-mation N0 vs. N1 or the overall number of positive lymph nodes. Usually the number of 0.2 is accepted as the sepa-ration level that indicates poor survival. Lymph node ratio > 0.2, together with vascular or perineural invasion, and a positive resection margin are all independent prognos-

15


www.avidscience.com

tic factors in determining long-term survival in patients undergoing resection for periampullarytumours [36-39].

Figure 7: Lymphadenectomy along the right side of the SMA (2): portal vein (1), superior mesenteric vein (2) and an aberrant common hepatic artery extending from

the SMA (3).

Lymphadenectomy in Distal PancreatectomyLymph node involvement in tumors located in the

body or tail of the gland is most frequently observed in the lymph nodes attached to the pancreas in the resected specimen. Standard lymphadenectomy during pancrea-tectomy for patients with pancreatic adenocarcinoma in the body or tail includes lymph nodes in stations 10 in the hilum of the spleen, 11 along the splenic artery, and 18 along the inferior border of the body and tail of the pancreas (Figure 8) [17].



Figuere 8: Standard lymphadenectomy in tumors located in the body or tail of the pancreas (lymph node stations

10,11,18).

Figure 9: А tumor localized at the boundary between the body and tail of the pancreas.

17


www.avidscience.com

Figure 10: А tumor localized at the boundary between the body and tail of the pancreas.

Lymph node station 9 is only suggested to be included in the resection when tumors are confined to the area of the body of the pancreas (Figure 9, Figure 10, Figure 11 and Figure 12). In patients undergoing left-sided pan-createctomy for malignant neoplasms, splenectomy is in-dicated to ensure adequate excision of the primary tumor and lymph nodes.

Two or three positive nodes were not associated with an impairment of the prognosis but had an equal survival to those patients with an N0 situation. A routine removal of the directly attached and peripancreatic nodes is a highly important part of the resection to achieve best oncological



outcome. In contrast, a more extended lymphadenectomy cannot be recommended from the available data, as this is, comparable to the setting of pancreatic head resection, associated with an increase in morbidity without proven oncological benefit.

Figure 11: A tumor (yellow circle) localized in the body of the pancreas. The lymphadenectomy includes lymph nodes in station 9 (lymph nodes around the celiac artery)–a.gastroduodenalis (1), common hepatic artery

(2), a.gastricasinistra (3), a.lienalis (4).

Lymphadenectomy in Total PancreatectomyFrom the oncological point of view, a multifocal pan-

creatic cancer as well as multiple metastases in the pan-creas are indications for a primary total pancreatectomy. This procedure may be necessary to achieve a tumor-free

19


www.avidscience.com

resection margin and R0 situation in centrally localized tumors of the pancreatic body. The removal of the gland as an en bloc pancreatectomy should be performed to avoid pancreatic transection with the risk of tumor cell spilling. Тhe volume of lymph node dissection in total pancrea-tectomy combinesа standard lymphadenectomy inPD and DP.

Figure 12: A specimen from a tumor located in the body of the pancreas in the center of the tumor is visible a duc-

tus pancreaticus.Prospective StudyWe studied the rate of metastatic lymph nodes accord-

ing to their localization in patients with resectable pancre-atic head adenocarcinoma, undergoing PD with standard lymphadenectomy [40]. Medical records of 116 consecu-tive patients treated for pancreas head adenocarcinoma at Naval Hospital of Varna, Bulgaria, between January 2004 and December 2012 were analyzed. Patients underwent a



classic Whipple’s procedure or pylorus preservation with standard lymphadenectomy. Pancreatogastrostomy in our modification was the preferred anastomotic technique [41]. Tumors were staged after resection according to the 7th edition of the American Joint Committee on Cancer Staging Manual [42]. Postoperatively, 82 (70,6%) patients received adjuvant 5-fluorouracil or gemcitabine-based regimens, including radiation as a component of adjuvant therapy. The follow-up from the date of surgery for all the patients was at least 18 month long. Only 48 (41,3%) patients are followed-up for 5 years and this prospective study still goes on. Postoperatively, they were evaluated according to their history and physical examination, se-rum carbohydrate antigen 19-9 (CA 19-9) levels, and CT scans of the chest, abdomen and pelvis every 3-6 months for 3 years and, subsequently, once annually. We studied the frequency of the lymph node involvement in all these patients, the lymph node stations most commonly affected by metastases after standard lymphadenectomy as well as the interdependence between the frequencies of the re-gional nodal metastases and the local/distant recurrence. Categorical variables were compared using chi-squared analysis. Continuous data were expressed as the median and range and compared using the Mann-Whitney test. Survival analysis was performed using the Kaplan-Meier method, and differences in survival were compared us-ing the log-rank test. The significance parameter was set at P<0,05. Statistical analysis was performed using SPSS

21


www.avidscience.com

version 17.0 (SPSS, Inc., Chicago, IL, USA).

Figure 13: Interdependence between the frequencies of regional nodal metastases and local/distant recurrences.

Morbidity and mortality rates after PD are 53,4% (n=62) and 5,1% (n=6), respectively. The number of re-trieved lymph nodes in the standard lymphadenectomy is ≥15. Among the 116 patients who have undergone PD, 81 (69,8%) patients are lymph-node positive. Recurrence data are available for 110 of them. The overall recurrence rate is 75,4% (83 patients) during the follow-up period. Clinicopathologic data are presented in Table 1.

The lymph-node areas most affected are station 13 (n=24), 17 (n=17) and 14 (n=13), followed by stations 12 (n=5) and 8a (n=2) (P=0,016) (Table 2).



Figure 14: Median disease-free survival and median over-all survival after pancreatic resection in patients with and

without lymph node.

Lymph-node involvement is significantly associated with the development of local recurrence. The latter oc-curs in 20% (n=22) of patients. Lymph-node involvement affects local recurrence rates, which occur in 20 of 75 (26,6%) and in two of 35 (5,7%) patients with and without lymph-node involvement, respectively (P=0,024) (Figure 13).

23


www.avidscience.com

Table 1: Clinical and pathologic features of 116 PC pa-tients submitted to PD.

Distant metastases occur in 55,4% (n=61) of patients. Regional nodal metastases from primary tumor correlate with the development of distant metastases, which occur in 68% (51 of 75) and 28,5% (10 of 35) of patients with and without positive regional lymph nodes, respectively (P=0,011). Vascular resection, margin status, T-stage and tumor size do not correlate with recurrence patterns. Post-operative radiation has not affected local recurrence rates. The 18-month survival estimates for lymph-node positive

Variable Patients, n (%) p-valueWithout lymph-node

metastases (n=35)With lymph-node metastases (n=81)

Gender, n (%) female male

11 (31,4)24 (68,5)

22 (27,1)59 (72,8)

0,343

Age, years, median (range) 63 (28-73) 61 (36-72) 0,152Postoperative adjuvant therapy, n (%) 28 (80,0) 54 (66,6) <0,001

Preoperative CA 19-9, U/ml, median (range)

41 (<1-1135) 181 (<1-6010) <0,001

Surgical procedure, n (%) Whipple’s procedure pylorus preservation

28 (80,0)7 (20,0)

53 (65,4)28 (34,5)

0,003

Vascular resection, n (%) 8 (22,8) 10 (12,3) <0,001Tumour size, cm, median (range) 2,5 (1-6) 3,0 (1,8-8) 0,005Tumour stage, n (%) T1 T2 T3

4 (11,4)2 (5,7)

29 (82,8)

0 (0)22 (27,2)59 (72,8)

<0,001

Histologic differentiation, n (%) good moderate poor

1 (2,8)

13 (37,1)21 (60)

4 (4,9)34 (42,0)43 (53,1)

0,235

Resection margin, n (%) R0 R1 R2

20 (57,1)14 (40,0)

1 (2,8)

46 (56,8)32 (39,5)

3 (3,7)

0,543

Recurrence, n (%) local recurrence distant recurrence

2 (5,7)

10 (28,5)20 (24,7)51 (62,9)

<0,018



group is 56% (n=42) but for lymph-node negative one - 80% (n=28), respectively. Median disease-free survival from the date of surgery is 8,5 months (95% CI 6,4-18) in 75 patients with and 14,0 months (95% CI 11,1-18) in 35 patients without lymph-node metastases, respectively (P = 0,022) (Figure 14).

Table 2: Distribution of lymph-node metastases.

Median overall survival from the date of surgery was 12 months (95% CI 10,4-18) in 75 patients with and 17 months (95% CI 15,3-18) in 35 patients without lymph-node metastases, respectively (P=0,035).

Conclusion PD with standard lymphadenectomy including at

least 15 lymph nodes should be the procedure of choice in adenocarcinoma of the pancreatic head. Extended lym-phadenectomy should not be applied routinely in patients with PC requiring PD or DP. The radical antegrade mod-ular pancreato-splenectomy is recommended for cancer location in the body or tail. Lymph node ratio ≥ 0.2 is an

Variable (nodal station) Patientsn %

Lymph node metastases in one nodal station 5 – suprapyloric 6 – infrapyloric 8a – nodes anterior to the common hepatic artery 12 b1, b2, c – nodes to the right of the hepatoduodenal ligament 13 a, b – posterior pancreaticoduodenal nodes 14 a, b – nodes to the right of the superior mesenteric artery 17 a, b – anterior pancreaticoduodenal nodes

0025

241317

00

2,46,1

29,618,020,9

Lymph-node metastases in two or more nodal stations 20 24,6

25


www.avidscience.com

independent adverse prognostic factor, which is powerful and useful for prognostic assessment for pancreatic can-cer. The illusion of ‘localized’ disease is betrayed by the high frequency of regional and distal nodal involvement, positive pancreatic and/or retroperitoneal margins fol-lowing resection, and the presence of distant micrometas-tases that commonly become clinically apparent shortly after surgery. We establish a directly proportional correla-tion between the presence of metastatic lymph nodes in-dependently of their number and the development of local recurrence and distant metastases. PC should be managed as a systemic disease, even in patients with evidence of only local or regional disease; consequently, any effort for local control can have little effect on survival. This finding confirms the fact that the biology of the disease remains the most important determining factor affecting the final outcome, despite the progress in surgical technique and systemic therapy.

AcknowledgementI thank N Dragnev and V Alexandrov for their sup-

port in data preparation.

References1. Hariharan D, Saied A, Kocher HM. Analysis of

mortality rates for pancreatic cancer across the world. HPB (Oxford). 2008; 10: 58-62.

2. Siegel R, Ma J, Zou A, Jemal A. Cancer statistics.



2014. CA Cancer J Clin. 2014; 64: 9-29.

3. Evans DB, Farnell MB, Lillemoe KD, Vollmer C Jr, Strasberg SM. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol. 2009; 16: 1736-1744.

4. World Cancer Research Fund International. Pan-creatic cancer statistics. London, England.

5. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H. Curative resection is the single most important factor determining outcome in patients with pan-creatic adenocarcinoma. Br J Surg. 2004; 91: 586-594.

6. Wenger FA, Peter F, Zieren J, Steiert A, Jacobi CA. Prognosis factors in carcinoma of the head of the pancreas. Dig Surg. 2000; 17: 29-35.

7. Cancer Research UK. Statistics and outlook for pancreatic cancer. Lonacon, England.

8. National Cancer Insitute. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations).

9. Rupp CC, Linehan DC. Extended lymphadenec-tomy in the surgery of pancreatic adenocarcino-ma and its relation to quality improvement issues. J Surg Oncol. 2009; 99: 207-214.

27


www.avidscience.com

10. Nimura Y, Nagino M, Takao S, Takada T, Miyaza-ki K, et al. Standard versus extended lymphad-enectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pan-creas: long-term results of a Japanese multicenter randomized controlled trial. J Hepatobiliary Pan-creat Sci. 2012; 19: 230-241.

11. Yeo CJ, Cameron JL, Lillemoe KD, Sohn T, Camp-bell K, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retro-peritoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg. 2002; 236: 355-366.

12. Büchler MW, Kleeff J, Friess H. Surgical treatment of pancreatic cancer. J Am Coll Surg. 2007; 205: S81-86.

13. McPhee JT, Hill JS, Whalen GF, Zayaruzny M, Litwin DE. Perioperative mortality for pancrea-tectomy: a national perspective. Ann Surg. 2007; 246: 246-253.

14. Gaedcke J, Gunawan B, Grade M, Szöke R, Liersch T. The mesopancreas is the primary site for R1 re-section in pancreatic head cancer: relevance for clinical trials. Langenbecks Arch Surg. 2010; 395: 451-458.



15. Zacharias T, Jaeck D, Oussoultzoglou E, Neuville A, Bachellier P. Impact of lymph node involve-ment on long term survival after R0 pancreati-coduodenectomy for ductal adenocarcinoma of the pancreas. J Gastrointest Surg. 2007; 11: 350-356.

16. Japan Pancreatic Society. Classification of Pancre-atic Carcinoma, 2nd English edn. Tokyo: Kane-hara Pub. 2003.

17. Tol JA, Gouma DJ, Bassi C, Dervenis C, Montorsi M, et al.; for the International Study Group on Pancreatic Surgery. Definition of a standard lym-phadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery. 2014; 156: 591-600.

18. Shimada K, Sakamoto Y, Sano T, Kosuge T. Prog-nostic factors after distal pancreatectomy with extended lymphadenectomy for invasive pancre-atic adenocarcinoma of the body and tail. Surgery. 2006; 139: 288-295.

19. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y. Impact of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for adenocarcinoma of the body or tail of the pancre-as. J Gastrointest Surg. 2009; 13: 85-92.

29


www.avidscience.com

20. Fujita T, Nakagohri T, Gotohda N, Takahashi S, Konishi M. Evaluation of the prognostic factors and significance of lymph node status in invasive ductal carcinoma of the body or tail of the pan-creas. Pancreas. 2010; 39: e48-54.

21. Pedrazzoli S, DiCarlo V, Dionigi R, Mosca F, Ped-erzoli P. Standard versus extended lymphadenec-tomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospec-tive, randomized study. Lymphadenectomy Study Group. Ann Surg. 1998; 228: 508-517.

22. Yeo CJ, Cameron JL, Sohn TA, Coleman J, Sauter PK, et al. Pancreaticoduodenectomy with or with-out extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma: comparison of morbidity and mortality and short-term out-come. Ann Surg. 1999; 229: 613-614.

23. Nguyen TC, Sohn TA, Cameron JL, Lillemoe KD, Campbell KA, et al. Standard vs. radical pancrea-ticoduodenectomy for periampullary adenocarci-noma: a prospective, randomized trial evaluating quality of life in pancreaticoduodenectomy survi-vors. J Gastrointest Surg. 2003; 7: 1-9.

24. Riall TS, Cameron JL, Lillemoe KD, Campbell K, Sauter PK, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended ret-



roperitoneal lymphadenectomy for periampullary adenocarcinomaâ€“part 3: update on 5-year sur-vival. J Gastrointest Surg. 2005; 9: 1191-1204.

25. Farnell MB, Pearson RK, Sarr MG, DiMagno EP, Burgart LJ, et al. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lym-phadenectomy in resectable pancreatic head ad-enocarcinoma. Surgery. 2005; 138: 618-630.

26. Jang JY, Kang MJ, Heo JS, Choi SH, Choi DW, et al. A prospective randomized controlled study comparing outcomes of standard resection and extended resection, including dissection of the nerve plexus and various lymph nodes, in patients with pancreatic head cancer. Ann Surg. 2014; 259: 656-664.

27. Michalski CW, Kleeff J, Wente MN, Diener MK, Büchler MW. Systematic review and meta-analy-sis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg. 2007; 94: 265-273.

28. Iqbal N, Lovegrove RE, Tilney HS, Abraham AT, Bhattacharya S. A comparison of pancreaticoduo-denectomy with extended pancreaticoduodenec-tomy: a meta-analysis of 1909 patients. Eur J Surg

31


www.avidscience.com

Oncol. 2009; 35: 79-86.

29. Ke K, Chen W, Chen Y. Standard and extended lymphadenectomy for adenocarcinoma of the pancreatic head: a meta-analysis and systematic review. J Gastroenterol Hepatol. 2014; 29: 453-462.

30. Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007; 141: 610-618.

31. Tomlinson JS, Jain S, Bentrem DJ, Sekeris EG, Maggard MA. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 2007; 142: 767-723.

32. Gutierrez JC, Franceschi D, Koniaris LG. How many lymph nodes properly stage a periampullary malignancy? J Gastrointest Surg. 2008; 12: 77-85.

33. Schwarz RE, Smith DD. Extent of lymph node retrieval and pancreatic cancer survival: informa-tion from a large US population database. Ann Surg Oncol. 2006; 13: 1189-1200.

34. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, et al. Exocrine and Endocrine Pancrea. AJCC Cancer Staging Manual, 7th edition. New York: Springer. 2010; 241.



35. Campbell F, Foulis AK, Verbeke CS. Dataset for the histopathological reporting of carcinomas of the pancreas, ampulla of Vater and common bile duct. 2010.

36. Huebner M, Kendrick M, Reid-Lombardo KM, Que F, Therneau T. Number of lymph nodes eval-uated: prognostic value in pancreatic adenocarci-noma. J Gastrointest Surg. 2012; 16: 920-926.

37. Valsangkar NP, Bush DM, Michaelson JS, Ferrone CR, Wargo JA. N0/N, PNL, or LNR? The effect of lymph node number on accurate survival predic-tion in pancreatic ductal adenocarcinoma. J Gas-trointest Surg. 2013; 17: 257-266.

38. Sahin TT, Fujii T, Kanda M, Nagai S, Kodera Y. Prognostic implications of lymph node metasta-ses in carcinoma of the body and tail of the pan-creas. Pancreas. 2011; 40: 1029-1033.

39. Farid S, Falk G, Joyce D, Chalikonda S, Walsh R, et al. Prognostic value of the lymph node ratio af-ter resection of periampullary carcinomas. HPB. 2014; 16: 582-591.

40. Kostov D, Kobakov G, Yankov D. Involvement of regional lymph nodes in patients with pancreatic head adenocarcinoma. Surg Chron. 2015; 20: 265-269.

33


www.avidscience.com

41. Kostov D, Kobakov G, Yankov D. Pancreatogas-trostomy with one continuous seromuscular cir-cular suture. Int J Surg Med. 2015; 1: 1-10.

42. Edge SB, Byrd DR, Compton CC, et al. AJCC Can-cer Staging Manual. New York: Springer. 2010.

chapter 3 lymphadenectomy in pancreatic cancer surgery · recent advances in pancreatic cancer...

Documents