Pancreatic Cancer in Southern Iran

This Article

Citations


Creative Commons License
Except where otherwise noted, this work is licensed under Creative Commons Attribution-NonCommercial 4.0 International License.

Article Information:


Group: 2010
Subgroup: Volume 12, Issue 6
Date: November 2010
Type: Original Article
Start Page: 624
End Page: 630

Authors:

  • N Ahmadloo
  • Department of Radiation Oncology, Shiraz University of Medical Science, Shiraz, Fars, Iran
  • F Bidouei
  • Department of Radiation Oncology, Shiraz University of Medical Science, Shiraz, Fars, Iran
  • Sh Omidvari
  • Department of Radiation Oncology, Shiraz University of Medical Science, Shiraz, Fars, Iran
  • M Ansari
  • Department of Radiation Oncology, Shiraz University of Medical Science, Shiraz, Fars, Iran
  • A Mosalaei
  • Department of Radiation Oncology, Shiraz University of Medical Science, Shiraz, Fars, Iran
  • M Mohammadianpanah
  • Department of Radiation Oncology, Nemazee Hospital, Shiraz University of Medical Sciences, Postcode: 71936-13311, Shiraz, Fars, Iran

      Correspondence:

      Affiliation: Department of Radiation Oncology, Nemazee Hospital, Shiraz University of Medical Sciences, Postcode: 71936-13311
      City, Province: Shiraz, Fars
      Country: Iran
      Tel: +98-711-6474320
      Fax: +98-711-6474320
      E-mail: mohpanah@sums.ac.ir, mohpanah@gmail.com

Abstract:


Background: Pancreatic cancer is still a health problem worldwide. The present study aimed to report the clinical characteristics, prognostic factors and treatment outcomes of 55 cases of pancreatic cancer and the literature review and analysis.

 

Methods: Between 1998 and 2008, 55 consecutive patients proven pathologically with adenocarcinoma of the pancreas and treated at our institution were enrolled. To find out the recent major series, a literature review was performed. We selected 35 major series including 257950 patients with pancreatic cancer for discussing the present study.

 

Results: Twenty-four patients (44%) had resectable disease, 19 (34%) had locally advanced disease, and 12 (22%) had metastatic disease. There were 22 women and 33 men ranging in age from 16 to 76 years, with a median age of 57 years at diagnosis. After a median follow-up of 15 months (range=2-104 months) for surviving patients, 14 patients were alive and without disease, 3 patients were alive with disease and 38 patients had died due to disease. The 5-year overall survival was 27%.

 

Conclusions: In this study and by analyzing the large data collection of recent major reported series, we found that pancreatic cancer tended to present at advanced stage, with a high frequency of locoregional and distant failure and a poor outcome. More effective local and systemic treatment for improving overall survival is needed.

Keywords: Pancreatic cancer; Chemotherapy; Radiotherapy; Surgery; Chemoradiation; Iran

Manuscript Body:


Introduction

 

Pancreatic cancer remains a major health problem around the world. This aggressive neoplasm is the 10th most common newly diagnosed cancer and the fourth leading cause of cancer mortality in the United States.1 An estimated 42,470 new cases of and 35,240 deaths from pancreatic cancer occurred in the United States in 2009. Mortality from pancreatic cancer has remained relatively stable and its survival has not improved substantially over the past 30 years.2 Pancreatic cancer has poor prognostic features at diagnosis, responds poorly to therapy and has short survival with approximately one- and five-year overall survival of 23% and 5% respectively.3,4 In resectable diseases, median survival following surgical resection has been reported as nearly 20 months with a 5-year survival of 7-25%.1,5-20 The majority of patients present with locally advanced and unresectable disease and has a median survival of approximately 4 to 12 months, with rare long-term survival. Median survival of patient with metastatic disease is less than 6 months.13,15,20-22

The present study aimed to report the characteristics, prognostic factors and treatment outcomes of 55 cases of pancreatic cancer and the literature review and analysis. In addition, this study represents a quantitative summary and analysis pooled data collection of 35 recent major related studies including more than 250000 cases.

 

 

Materials and Methods

 

Between 1998 and 2008, 55 consecutive patients diagnosed with adenocarcinoma of the pancreas and treated at Department of Radiation Oncology, Nemazee Hospital, affiliated to Shiraz University of Medical Sciences entered our study. The possibility of selection bias cannot be ruled out, because our institution is a referral cancer center, and few patients with metastatic pancreatic cancer might not be referred to receive local treatment and have been excluded from the study. The study included all patients with histopathologically proven diagnosis of adenocarcinoma of the pancreas. Clinical evaluation included history and physical examination, complete blood count, renal function tests, serum electrolytes, liver function tests, chest x-ray, and ultrasonography and computed tomography of abdomen and pelvis. Based on the clinical, surgical, pathological and imaging findings, the patients were categorized to resectable (stage I-II), locally advanced (stage III) and metastatic (stage IV) forms. Twenty-four patients were treated surgically followed by adjuvant chemotherapy and/or radiotherapy, 24 patients with combined radiotherapy and chemotherapy, 4 with radiotherapy alone, and 3 with chemotherapy alone.

Surgical treatment consisted of Whipple's procedure in patients with resectable diseases, or palliative biliary bypass and biopsy in patients with unresectable or metastatic disease. The chemotherapy regimen mainly consisted of 5-fluorouracil- (5-FU) or gemcitabine-based regimen. Twenty-seven patients (52%) received 5-FU 500 mg/m2 on days 1-3 every 4 weeks and 22 patients (40%) received gemcitabine 1000 mg/m2 on days 1, 8 and 15 every 4 weeks. The sixth edition of the American Joint Committee on Cancer (AJCC) staging classification was used for staging the disease. Forty-six patients received adjuvant or definitive external beam radiotherapy using cobalt-60 units or 9 MV X-ray photons from a linear accelerator. A median dose of 50 Gy (range 40 to 60 Gy) was delivered via a daily fraction of 1.8-2 Gy, with five fractions per week. Disease-free survival was calculated from the date of registration to the date of disease relapse at any site. Overall survival was calculated from the date of registration to the date of death due to any cause. Univariate analysis for disease-free survival and overall survival rates was performed using the Kaplan–Meier method, and prognostic factors were compared using the log-rank test. Multiple-covariate analysis was performed using the stepwise Cox’s proportional hazards regression model. The hazard ratio for death, with the 95% confidence interval (CI), was calculated for the treatment groups. The stratified log-rank test was used to compare treatment results in each disease group. P values less than 0.05 were considered statistically significant.

 

 

Results

 

There were 22 women and 33 men ranging in age from 16 to 76 years, with a median age of 57 years at diagnosis. The peak incidence was during the sixth and seventh decades of life in both sexes. Thirty-eight patients were ≥50 years old at presentation and 17 patients were <50 years old. Twenty-four patients (44%) had resectable (stage I-II) disease, 19 (34%) had locally advanced (stage III) disease, and 12 (22%) had metastatic (stage IV) disease.

Twenty-four patients (44%) underwent Whipple's procedure followed by adjuvant chemotherapy and/or radiotherapy. In patients who underwent Whipple's procedure, 25% had lymph node involvement and 75% were lymph node negative, and resection margins were clear in 83% and involved in 17% of cases. In addition, in this group, lymphovascular or perineural invasion was found in 13 (54%) cases.

After a median follow up of 15 months for surviving patients, 14 patients were alive and without disease, 3 were alive with disease, and 38 had died due to the disease. Forty-one patients (74.5%) developed local, regional or distant failures. Recurrences consisted of 10 patients (18.2%) with locoregional or distant metastases. Median survival was 15 months for surviving patients. The one- and 5-year overall survival was 54.5% and 27% respectively.

On univariate analysis for overall survival, age (p=0.04), stage of disease (p=0.001), resectability (p=0.001), and resection margin status in operated patients (p=0.004) were prognostic factors. Lymph node status, lymphovascular or perineural invasion and type of adjuvant treatment (radiotherapy vs. chemotherapy or both) were found not to be prognostic factors for overall survival (Table 1).

 

 

Table 1: Univariate analysis of prognostic factors for clinical outcome

Prognostic factors

Pts

(n)

1-yr OS (%)

2-yr OS (%)

5-yr OS

 (%)

P value

HR

CI

Age

  <55 years

  ≥55 years

 

17

38

 

70.6

47.4

 

49.9

25.9

 

49.9

17.0

 

 

0.040

 

 

2.138

 

 

0.977-4.676

Sex

  Male

  Female

 

33

22

 

51.5

59.1

 

30.5

37.5

 

24.4

31.3

 

 

0.479

 

 

0.791

 

 

0.408-1.533

Resectability

   Resected

   Non-resected

 

24

31

 

79.2

35.5

 

64.6

  9.0

 

50.7

  9.0

 

 

0.001

 

 

4.224

 

 

1.990-8.965

Stage

   I-II

   III

   IV

 

24

19

12

 

79.2

36.8

33.3

 

64.6

15.8

00.0

 

50.7

15.8

00.0

 

 

 

0.001

 

 

 

2.255

 

 

 

1.495-3.402

Margin status

   Clear

   Involved

 

20

  4

 

85.0

50.0

 

73.2

25.0

 

62.8

00.0

 

 

0.004

 

 

5.548

 

 

1.468-20.976

LN status

   Free

   Involved

 

18

  6

 

88.9

50.0

 

75.2

33.3

 

54.2

33.3

 

 

0.111

 

 

0.372

 

 

0.103-1.334

LV or PN invasion

   Present

   Absent

 

13

11

 

69.2

90.9

 

59.3

70.7

 

31.6

70.7

 

 

0.126

 

 

0.365

 

 

0.094-1.418

Radiotherapy

   Received

   No received

 

46

  9

 

54.3

55.6

 

32.6

37.0

 

25.6

37.0

 

 

0.624

 

 

0.794

 

 

0.310-2.035

Chemotherapy

   Gemcitabine-based

   5-FU-based

   No Ch.T

 

22

27

  6

 

59.1

51.9

50.0

 

39.2

29.6

25.0

 

31.3

24.7

25.0

 

 

 

0.820

 

 

 

1.122

 

 

 

0.684-1.841

Total

55

54.5

33.2

27

-

-

-

Pts, Patients; yr, year; OS, Overall Survival; LN, Lymph Node; LV, Lymphovascular; PN, Perineural; ChT, Chemotherapy; HR, Hazard Ratio; CI, Confidence Interval

 

 

On multivariate analysis, only resectability (hazard ratio=4.224; 95% confidence interval =1.990-8.965, p<0.001), stage of disease (hazard ratio=2.255; 95% confidence interval=1.495-3.402, p<0.001) and resection margin status (hazard ratio=5.548; 95% confidence interval=1.468-20.976, p=0.004) retained statistical significance. 

 

 

Discussion

 

Pancreatic cancer is one of the most rapidly fatal cancer, and most cases are first diagnosed at advanced clinical stages. This malignancy is the fourth leading cause of cancer death following the cancers of the lung, colon and breast. Pancreatic cancer usually occurs in the seventh and eight decades of life and rarely in adults less than 40 years of age.2,4 In the present study, the median age of our patients were 57 years, which was younger that of the results of the literature review in which the average median age of 42972 patients in the reported series was 71 years3,5,7-11,14,17-29 (Table 2). In a study in southern Iran, the crude incidence rate and ASR for pancreatic cancer in males were 0.26 and 0.42 respectively while these figures in females were 0.21 and 0.38 respectively confirming our results.30

 

 

Table 2: Characteristics and treatment outcome of 257950 patients with pancreatic cancer in 34 major reported series and present study

Author

Pts (n) 

Median age 

M/F ratio 

% of Resectable disease 

Median survival

1-year

OS (%)

5-year

OS (%)

Baxter3

  36553

72

0.95

  33

  4

23

  5

Zhang4

  70518

-

0.99

-

-

-

-

Garcea5

        62

62.5

1.2

-

54

-

-

Scodan6

        41

-

1.6

  73

  9.4

41

-

Chiang7

      159

59

1.5

  40

-

51.3

12.5

Corsini8

      472

67

1.2

100

21.6

-

28

Sohn9

      616

66

1.2

-

17

63

17

Ahmad10

      116

66

0.8

-

16

60

19

Eloubeidi11

    2230

71

1

  12.5

  4.7

-

-

Wang12

        18

-

0.8

-

21.6

88

-

Tani13

      172

-

1.3

    0

10.9

40.5

  0 

Murakami14

        89

68

1.4

  66

12.1

59

  7

Cress15

  10612

-

-

  15.8

-

-

-

Sperti16

      113

-

1.4

-

-

80

12

Hudson17

        91

69

1

    0

  9.2

34.1

-

Lim18

      396

72

1

-

17.6

60

-

Magistrelli19

        73

62

1.5

  80

16

60

13

Ueda20

      140

66

1.3

-

14.5

-

12.3

Soriano-Izquierdo21

        94

63

0.9

-

18

63

  8

Herman22

      616

68

1.1

-

17.9

-

20

Tinkl23

        38

61

1.7

-

25

68

30

You24

      219

60

1.4

-

14

-

14.2

Hattangadi25

        86

62.5

0.9

-

22

76

-

Lange26

        24

63

0.6

    0

10

-

-

Ohguri27

        29

64

1.4

-

16.1

-

-

Ogawa28

      870

64

-

  31

-

-

-

Sharp29

    3173

72

097

    7

  3.5

13.7

-

Wood30

  17919

-

0.97

-

-

12.7

2.5

Benassai31

      336

-

1.4

  24

17

68

18.7

Lefebvre32

    1175

-

1.1

  11

  4

-

-

Allen-Mersh33

    5881

-

-

  34

-

10

  3

Sener34

100313

-

-

    9

-

23.4

  5.2

Gao35

      134

-

-

-

24.7

67.1

17.6

Bossard36

    4517

-

-

-

-

-

  6

Present study

        55

57

1.5

  44

15

54.5

27

Total

257950

71.4

0.98

  16*

  5.2*

22.3*

  5*

*Studies including selectively localized or locally advanced disease were excluded for this mean value

 

 

In the present study, males represented a higher proportion of cases, with a male/female ratio of 1.5; however, in the literature review, there was no significant difference and the male/female ratio was nearly equal to one (range from 0.6 to 1.7) in 27 studies including 132584 patients.3-14,16-27,29-33

Pancreatic cancer usually presents late and approximately 80-95% of patients are diagnosed with locally advanced and metastatic disease. Therefore, the vast majority of these patients have unresectable disease at presentation.11,29 In the literature review and according to the pooled data from 14 series including 160385 cases, only 16% of patients had resectable disease at the diagnosis.3,6-8,11,14,15,19,28,29,32-35 However, in present study, 44% of patients had resectable disease, which is significantly higher than our mean value.

Pancreatic cancer is a highly fatal malignant tumor with a median survival of only less than 6 months in most large series.3 In our series, the median survival was 15 months, which is higher than 5.2 months for 47051 patients in the literature. This is mainly due to the higher frequency of resectable disease in our series. In addition, the one-year survival of our series was 54.5% compared with 22.3% for 166639 patients in the literature. Similarly, 5-year survival of our series was 27%, which was higher than 22.3% for 166639 patients in the literature.3,5,6,8-14,17-27,29,32,33,36,37

Comparable to other studies, we found that tumor, patient, and treatment factors affect survival in patients with pancreatic cancer.38-44 Therefore, the present study concluded that older age (age ≥ 50 years), a higher disease stage, unresectable forms, and pathologic involved resection margin are associated with poorer survival.

In contrary to some studies, in this study, lymph node status and lymphovascular invasion or perineural invasion did not have any relationship with survival, which can be due to small amount of our patients.45-47 In addition, type of adjuvant treatment modality (radiotherapy vs. chemotherapy or both) showed no effect on overall survival, which may be due to suboptimal adjuvant chemotherapy and radiotherapy used in these patients.48-50 In the current study, liver metastasis and locoregional recurrences were the dominant failures, which are consistent with the results of most reported series in the literature.6,12,20,24,27

Currently, surgical resection remains the only potentially curative treatment for locoregional disease.51 In an attempt to increase resection rates, reduce positive resection margins, and improve locoregional control and survival, chemotherapy has been investigated as an adjuvant or neoadjuvant to locoregional treatment. It has been well-established that adjuvant chemotherapy improves survival in patients with pancreatic cancer; however, neoadjuvant treatments should be limited to controlled clinical trial. Concurrent chemoradiation remains the mainstay of therapy for unresectable pancreatic cancer. This combined modality increases resectability rates in neoadjuvant setting and improves locoregional control as adjuvant treatment. However, its impact on overall survival still remains undefined.50-52

 

Conflict of interest: None declared.

References: (52)

  1. Yokoyama Y, Nimura Y, Nagino M. Advances in the treatment of pancreatic cancer: limitations of surgery and evaluation of new therapeutic strategies. Surg Today 2009;39: 466-75. [19468801] [doi:10.1007/s00595-008-3904-6]
  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49. [19474385] [doi:10.3322/caac.20006]
  3. Baxter NN, Whitson BA, Tuttle TM. Trends in the treatment and outcome of pancreatic cancer in the United States. Ann Surg Oncol 2007;14:1320-6. [17225980] [doi:10.1245/s10434-006-9249-8]
  4. Zhang J, Dhakal I, Yan H, Phillips M, Kesteloot H; SEER Cancer Registries. Trends in pancreatic cancer incidence in nine SEER Cancer Registries, 1973-2002. Ann Oncol 2007;18:1268-79. [17488731] [doi:10.1093/annonc/mdm123]
  5. Garcea G, Dennison AR, Ong SL, Pattenden CJ, Neal CP, Sutton CD, Mann CD, Berry DP. Tumour characteristics predictive of survival following resection for ductal adenocarcinoma of the head of pancreas. Eur J Surg Oncol 2007;33:892-7. [17398060] [doi:10.1016/j.ejso.2007.02.024]
  6. Le Scodan R, Mornex F, Girard N, Mercier C, Valette PJ, Ychou M, Bibeau F, Roy P, Scoazec JY, Partensky C. Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann Oncol 2009;20:1387-96. [19502533] [doi:10.1093/annonc/mdp015]
  7. Chiang KC, Yeh CN, Lee WC, Jan YY, Hwang TL. Prognostic analysis of patients with pancreatic head adenocarcinoma less than 2 cm undergoing resection. World J Gastroenterol 2009;15:4305-10. [19750574] [doi:10.3748/wjg.15.4305]
  8. Corsini MM, Miller RC, Haddock MG, Donohue JH, Farnell MB, Nagorney DM, Jatoi A, McWilliams RR, Kim GP, Bhatia S, Iott MJ, Gunderson LL. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975-2005). J Clin Oncol 2008;26:3511-6. [18640932] [doi:10.1200/JCO.2007.15.8782]
  9. Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, Coleman J, Hruban RH, Lillemoe KD. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000;4:567-79. [11307091] [doi:10.1016/S1091-255X(00)80105-5]
  10. Ahmad NA, Lewis JD, Ginsberg GG, Haller DG, Morris JB, Williams NN, Rosato EF, Kochman ML. Long term survival after pancreatic resection for pancreatic adenocarcinoma. Am J Gastroenterol 2001;96:2609-15. [11569683] [doi:10.1111/j.1572-0241.2001.04123.x]
  11. Eloubeidi MA, Desmond RA, Wilcox CM, Wilson RJ, Manchikalapati P, Fouad MM, Eltoum I, Vickers SM. Prognostic factors for survival in pancreatic cancer: a population-based study. Am J Surg 2006;192:322-9. [16920426] [doi:10.1016/j.amjsurg.2006.02.017]
  12. Wang MLC, Foo KF. Adjuvant chemoradiotherapy for high risk pancreatic cancer. Singapore Med J 2009;50:43-8. [19224083]
  13. Tani M, Kawai M, Terasawa H, Ina S, Hirono S, Shimamoto T, Miyazawa M, Uchiyama K, Yamaue H. Prognostic factors for long-term survival in patients with locally invasive pancreatic cancer. J Hepatobiliary Pancreat Surg 2007;14:545-50. [18040618] [doi:10.1007/s00534-007-1209-6]
  14. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Ohge H, Sueda T. Postoperative adjuvant chemotherapy improves survival after surgical resection for pancreatic carcinoma. J Gastrointest Surg 2008;12:534-41. [18026816] [doi:10.1007/s11605-007-0407-5]
  15. Cress RD, Yin D, Clarke L, Bold R, Holly EA. Survival among patients with adenocarcinoma of the pancreas: a population-based study. Cancer Causes Control 2006;17:403-9. [16596292] [doi:10.1007/s10552-005-0539-4]
  16. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg 1996;83:625-31. [8689203] [doi:10.1002/bjs.1800830512]
  17. Hudson E, Hurt C, Mort D, Brewster AE, Iqbal N, Joseph G, Crosby TD, Mukherjee S. Induction Chemotherapy Followed by Chemoradiation in Locally Advanced Pancreatic Cancer: An Effective and Well-tolerated Treatment. Clin Oncol (R Coll Radiol) 2010;22:27-35. [19896352] [doi:10.1016/j.clon.2009.09.024]
  18. Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg 2003;237:74-85. [12496533] [doi:10.1097/00000658-200301000-00011]
  19. Magistrelli P, Antinori A, Crucitti A, La Greca A, Masetti R, Coppola R, Nuzzo G, Picciocchi A. Prognostic factors after surgical resection for pancreatic carcinoma. J Surg Oncol 2000;74:36-40. [10861607] [doi:10.1002/1096-9098(200005)74:1<36::AID-JSO9>3.0.CO;2-F]
  20. Ueda M, Endo I, Nakashima M, Minami Y, Takeda K, Matsuo K, Nagano Y, Tanaka K, Ichikawa Y, Togo S, Kunisaki C, Shimada H. Prognostic factors after resection of pancreatic cancer. World J Surg 2009;33:104-10. [19011933] [doi:10.1007/s00268-008-9807-2]
  21. Soriano-Izquierdo A, Adet AC, Gallego R, Miquel R, Castells A, Pellisé M, Nadal C, López-Boado MA, Piqué JM, Gascón P, Conill C, Bombí A, Fernández-Cruz L, Maurel J, Navarro S. Prediction of prognosis of patients with pancreatic adenocarcinoma with curative intent resection by means of histologic grade and pathologic N stage. Med Clin (Barc) 2009;132:163-71. [19211081] [doi:10.1016/j.medcli.2008.07.012]
  22. Herman JM, Swartz MJ, Hsu CC, Winter J, Pawlik TM, Sugar E, Robinson R, Laheru DA, Jaffee E, Hruban RH, Campbell KA, Wolfgang CL, Asrari F, Donehower R, Hidalgo M, Diaz LA Jr, Yeo C, Cameron JL, Schulick RD, Abrams R. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol 2008;26:3503-10. [18640931] [doi:10.1200/JCO.2007.15.8469]
  23. Tinkl D, Grabenbauer GG, Golcher H, Meyer T, Papadopoulos T, Hohenberger W, Sauer R, Brunner TB. Downstaging of pancreatic carcinoma after neoadjuvant chemoradiation. Strahlenther Onkol 2009;185:557-66. [19756421] [doi:10.1007/s00066-009-1977-9]
  24. You DD, Lee HG, Heo JS, Choi SH, Choi DW. Prognostic factors and adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. J Gastrointest Surg 2009;13:1699-706. [19582512] [doi:10.1007/s11605-009-0969-5]
  25. Hattangadi JA, Hong TS, Yeap BY, Mamon HJ. Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma. Cancer 2009;115:3640-50. [19514088] [doi:10.1002/cncr.24410]
  26. de Lange SM, van Groeningen CJ, Meijer OW, Cuesta MA, Langendijk JA, van Riel JM, Pinedo HM, Peters GJ, Meijer S, Slotman BJ, Giaccone G. Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer. Eur J Cancer 2002;38:1212-7. [12044508] [doi:10.1016/S0959-8049(02)00076-X]
  27. Ohguri T, Imada H, Yahara K, Narisada H, Morioka T, Nakano K, Korogi Y. Concurrent chemoradiotherapy with gemcitabine plus regional hyperthermia for locally advanced pancreatic carcinoma: initial experience. Radiat Med 2008;26:587-96. [19132489] [doi:10.1007/s11604-008-0279-y]
  28. Ogawa K, Ito Y, Karasawa K, Ogawa Y, Onishi H, Kazumoto T, Shibuya K, Shibuya H, Okuno Y, Nishino S, Ogo E, Uchida N, Karasawa K, Nemoto K, Nishimura Y; JROSG Working Subgroup of Gastrointestinal Cancers. Patterns of Radiotherapy Practice for Pancreatic Cancer in Japan: Results of the Japanese Radiation Oncology Study Group (JROSG) Survey. Int J Radiat Oncol Biol Phys 2010;77:743-50. [19879060] [doi:10.1016/j.ijrobp.2009.05.063]
  29. Sharp L, Carsin AE, Cronin-Fenton DP, O'Driscoll D, Comber H. Is there under-treatment of pancreatic cancer? Evidence from a population-based study in Ireland. Eur J Cancer 2009;45:1450-9. [19268569] [doi:10.1016/j.ejca.2009.01.033]
  30. Mehrabani D, Tabei SZ, Heydari ST, Shamsina SJ, Shokrpour N, Amini M, Masoumi SJ, Julaee H, Farahmand M, Manafi A. Cancer occurrence in Fars Province, Southern Iran. Iran Red Crescent Med J 2008;10:314-322.
  31. Wood HE, Gupta S, Kang JY, Quinn MJ, Maxwell JD, Mudan S, Majeed A. Pancreatic cancer in England and Wales 1975-2000: patterns and trends in incidence, survival and mortality. Aliment Pharmacol Ther 2006;23:1205-14. [16611282] [doi:10.1111/j.1365-2036.2006.02860.x]
  32. Benassai G, Mastrorilli M, Quarto G, Cappiello A, Giani U, Forestieri P, Mazzeo F. Factors influencing survival after resection for ductal adenocarcinoma of the head of the pancreas. J Surg Oncol 2000;73:212-8. [10797334] [doi:10.1002/(SICI)1096-9098(200004)73:4<212::AID-JSO5>3.0.CO;2-D]
  33. Lefebvre AC, Maurel J, Boutreux S, Bouvier V, Reimund JM, Launoy G, Arsene D. Pancreatic cancer: incidence, treatment and survival trends--1175 cases in Calvados (France) from 1978 to 2002. Gastroenterol Clin Biol 2009;33:1045-51. [19773140] [doi:10.1016/j.gcb.2009.04.011]
  34. Allen-Mersh TG, Earlam RJ. Pancreatic cancer in England and Wales: surgeons look at epidemiology. Ann R Coll Surg Engl 1986;68:154-8. [3729266]
  35. Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg 1999;189:1-7. [10401733] [doi:10.1016/S1072-7515(99)00075-7]
  36. Gao CT, Li HK, Li Q. Factors influencing survival of patients with cancer of the pancreatic head after resection. Zhonghua Zhong Liu Za Zhi 2009;31:554-7. [19950708]
  37. Bossard N, Velten M, Remontet L, Belot A, Maarouf N, Bouvier AM, Guizard AV, Tretarre B, Launoy G, Colonna M, Danzon A, Molinie F, Troussard X, Bourdon-Raverdy N, Carli PM, Jaffre A, Bessaguet C, Sauleau E, Schvartz C, Arveux P, Maynadie M, Grosclaude P, Esteve J, Faivre J. Survival of cancer patients in France: a population-based study from The Association of the French Cancer Registries (FRANCIM). Eur J Cancer 2007;43:149-60. [17084622] [doi:10.1016/j.ejca.2006.07.021]
  38. Murphy MM, Simons JP, Hill JS, McDade TP, Chau Ng S, Whalen GF, Shah SA, Harrison LH, Jr., Tseng JF. Pancreatic resection: a key component to reducing racial disparities in pancreatic adenocarcinoma. Cancer 2009;115:3979-90. [19514091] [doi:10.1002/cncr.24433]
  39. Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Gomez HF, Sun CC, Crane CH, Wolff RA, Evans DB. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004;8:935-49. [15585381] [doi:10.1016/j.gassur.2004.09.046]
  40. Henne-Bruns D, Vogel I, Luttges J, Kloppel G, Kremer B. Ductal adenocarcinoma of the pancreas head: survival after regional versus extended lymphadenectomy. Hepatogastroenterology 1998;45:855-66. [9684147]
  41. Cleary SP, Gryfe R, Guindi M, Greig P, Smith L, Mackenzie R, Strasberg S, Hanna S, Taylor B, Langer B, Gallinger S. Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg 2004;198:722-31. [15110805] [doi:10.1016/j.jamcollsurg.2004.01.008]
  42. Kuhlmann KF, de Castro SM, Wesseling JG, ten Kate FJ, Offerhaus GJ, Busch OR, van Gulik TM, Obertop H, Gouma DJ. Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer 2004;40:549-58. [14962722] [doi:10.1016/j.ejca.2003.10.026]
  43. Greer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 1993;165:68-72. [8380315] [doi:10.1016/S0002-9610(05)80406-4]
  44. Park JK, Yoon YB, Kim YT, Ryu JK, Yoon WJ, Lee SH. Survival and prognostic factors of unresectable pancreatic cancer. J Clin Gastroenterol 2008;42:86-91. [18097296] [doi:10.1097/01.mcg.0000225657.30803.9d]
  45. Delcore R, Rodriguez FJ, Forster J, Hermreck AS, Thomas JH. Significance of lymph node metastases in patients with pancreatic cancer undergoing curative resection. Am J Surg 1996;172:463-8. [8942545] [doi:10.1016/S0002-9610(96)00237-1]
  46. Nakaghori T, Kinoshita T, Konishi M, Takahashi S, Gotohda N. Nodal involvement is the strongest predictor of poor survival in patients with invasive adenocarcinoma of the head of the pancreas. Hepatogastroenterol 2006;53:447-51. [16795990]
  47. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:586-94. [15122610] [doi:10.1002/bjs.4484]
  48. Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, Bassi C, Dervenis C, Fernandez-Cruz L, Lacaine F, Buckels J, Deakin M, Adab FA, Sutton R, Imrie C, Ihse I, Tihanyi T, Olah A, Pedrazzoli S, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. 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;234:758-68. [11729382] [doi:10.1097/00000658-200112000-00007]
  49. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403-13. [9196156]
  50. Morganti AG, Massaccesi M, La Torre G, Caravatta L, Piscopo A, Tambaro R, Sofo L, Sallustio G, Ingrosso M, Macchia G, Deodato F, Picardi V, Ippolito E, Cellini N, Valentini V. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol 17:194-205. [19856029] [doi:10.1245/s10434-009-0762-4]
  51. Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Postgrad Med J 2008;84:478-97. [18940950] [doi:10.1136/gut.2006.103333]
  52. Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. Jop 2008;9:99-132. [18326920]