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  • Research article
  • Open Access
  • Open Peer Review

Predictors of distant metastasis on exploration in patients with potentially resectable pancreatic cancer

Contributed equally
BMC Gastroenterology201818:168

https://doi.org/10.1186/s12876-018-0891-y

  • Received: 6 August 2018
  • Accepted: 23 October 2018
  • Published:
Open Peer Review reports

Abstract

Background

Patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC) are frequently found to be unresectable on exploration due to small distant metastasis. This study was to investigate predictors of small distant metastasis in patients with potentially resectable PDAC.

Methods

Patients who underwent surgical exploration for potentially resectable PDAC from 2013 to 2014 were reviewed retrospectively and divided into two groups according to whether distant metastases were encountered on exploration. Then, univariate and multivariate logistic regression analyses were used to identify predictors of distant metastasis. A scoring system to predict distant metastasis of PDAC on exploration was constructed based on the regression coefficient of a multivariate logistic regression model.

Results

A total of 235 patients were included in this study. Mean age of the study population was 61.7 ± 10.4 years old. Upon exploration, distant metastases were found intraoperatively in 62 (26.4%) patients, while the remaining 173 were free of distant metastases. Multivariate logistic regression analysis identified that age ≤ 62 years old (p < 0.001), male sex (p = 0.011), tumor size ≥4.0 cm (p < 0.001), alanine aminotransferase level (ALT) < 125 U/L (p < 0.001), and carbohydrate antigen (CA19–9) level ≥ 385 U/mL (p < 0.001) were independent risk factors for occult distant metastasis of PDAC. A preoperative scoring system (0–8 points) for distant metastasis on exploration was constructed using these five factors. The receiver operating characteristic curves showed that the area under the curve of this score was 0.85. A score of 6 points was suggested to be the optimal cut-off value, and the sensitivity and specificity were 85% and 69%, respectively.

Conclusions

Distant metastasis is still frequently encountered on exploration for patients with potentially resectable PDAC. Younger age, male sex, larger tumor size, low ALT level and high CA19–9 level are independent predictors of unexpected distant metastasis on exploration.

Keywords

  • Distant metastasis
  • Pancreatic cancer
  • Predictive factor
  • Surgical exploration

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most dismal malignancies with an overall 5-year survival rate of < 7% [1, 2]. Despite enormous efforts directed at the treatment of PDAC, radical resection remains the most effective treatment modality, and it increases the 5-year survival rate for PDAC patients to 10–25% [35]. However, due to a lack of presentations at early stages and the aggressive nature of this disease, the majority of PDAC patients present an unresectable disease at the time of diagnosis, and only around 20% of newly diagnosed PDAC patients were suitable candidates for curable surgical resection [6].

Multidetector computed tomography (MDCT) is currently the optimal imaging modality for preoperative diagnosis and staging of PDAC [7, 8]. However, this imaging modality has a poor sensitivity for identifying small liver or peritoneal metastasis [7, 9]. Among the patients subjected to surgical exploration, a significant proportion (40%) of them are found to be unresectable due to occult distant metastasis or infiltration of local structures [1012]. The proportion of patients successfully resected during surgical exploration might be as low as 50% [12, 13].

For patients with distant occult metastasis, surgical resection is unnecessary as it does not prolong survival in the overwhelming majority of patients [14, 15]. Besides, unnecessary surgical exploration often delays administration of other treatments, for example systematic chemotherapy, which currently is the preferred treatment for metastatic PDAC patients [16]. Therefore, it is important to differentiate PDAC patients with distant metastasis from those with truly resectable cancers to avoid unnecessary surgery and offer these patients tailored treatments in a timely manners. The objective of this retrospective study was to analyze the predictive factors for distant occult metastasis in patients with resectable PDAC based on preoperative MDCT.

Methods

Study design and patients

This was a single institution, retrospective study, from a high-volume center, the Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, China. All patients who underwent elective pancreatic surgery at our unit between January 2014 and December 2015 were reviewed retrospectively. Only patients with a final diagnosis of PDAC were included. Exclusion criteria were as follows: 1) patients underwent an operation with palliative intent, 2) patients without preoperative internal MDCT, and 3) patients with distant metastasis detected with preoperative MDCT. All patients underwent a triple-phase 16-row MDCT, consisting of unenhanced, early arterial, and venous phases.

Patients were included in the “with metastasis” (WM) group when distant metastasis, such as liver and peritoneal metastasis, was encountered during surgery. The remaining patients were included in the “no metastasis” (NM) group. During the surgery, distant metastasis was discovered through manual palpation by experienced surgeons and further confirmed with frozen resection. Intra-operative ultrasound was not used.

Data collected included age at diagnosis; sex; drinking and smoking history; comorbidities (Hypertension and Diabetes Mellitus); chief complaint (with pain or without pain); preoperative laboratory data, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), albumin, alpha fetoprotein (AFP), carbohydrate antigen (CA19–9), and carcinoembryonic antigen (CEA); tumor size and location on MDCT; and time interval between MDCT and operation. The possible risk factors for distant metastasis were then examined statistically. Data were obtained from the patients’ medical records and the hospital electronic database. All the imaging results were reviewed by a dedicated radiologist. This study was approved by the institutional review board with a waiver of informed consent (No. 2016-SR-210).

Statistical analysis

Quantitative variables are presented as the mean ± standard deviation and qualitative variables are expressed as absolute and relative frequencies. Comparisons between the WM and NM groups are performed using the Student’s t-test or Chi-square test accordingly. The association between the predictive factors and presence of distant metastasis was first evaluated by univariate logistic regression. Factors with a p < 0.1 in the univariate regression analysis were included in multivariate logistic regression analysis. Backward stepwise elimination was used to exclude variables with p > 0.05 from the model. Continuous variables were divided into two groups according to the mean value of each parameter. All statistical analyses were performed using Stata/SE version 10.0 for Windows (StataCorp, Texas, USA). All tests for significance were two-sided and a value of p < 0.05 was considered statistically significant.

Results

Demographic and clinicopathologic characteristics

In the study period, a consecutive series of 501 patients with PDAC underwent laparotomy in our center. Of these, 26 patients were excluded because they had unresectable disease detected radiologically and underwent an operation with palliative intent. Another 240 patients were excluded for having no internal MDCT: 218 didn’t have any image studies in our hospital, and 22 had only Magnetic Resonance Imaging or magnetic resonance cholangiopancreatography or positron emission tomography/computed tomography other than MDCT. Ultimately, a total of 235 patients were included in the analysis (Fig. 1).
Fig. 1
Fig. 1

Flow diagram showing selection of patients for inclusion in the study

All the included 235 patients underwent upfront surgery, and received no neoadjuvant therapy. Distant metastasis was found in 62 (26.4%) patients, including 31 liver metastases and 31 peritoneal metastases. Of the 62 patients with metastases, three patients underwent pancreaticoduodenectomy for primary cancer and the remaining patients underwent different palliative procedures accordingly. Of the 173 NM patients, 164 patients underwent resection successfully and 9 patients underwent palliative operations because the tumor was locally advanced. Details of the procedures are shown in Table 1.
Table 1

Procedures performed for 235 patients

 

Total

(n = 235)

No Metastasis

(n = 173)

With Metastasis

(n = 62)

Resected

167

164

3

 PD/PPPD

124

121

3

 Distal pancreatectomy

39

39

0

 Total pancreatectomy

1

1

0

 Appleby Operation

3

3

0

Not Resected

68

9

59

 Double Bypass

13

1

12

 Biliary Bypass

9

4

5

 Gastric Bypass

4

0

4

 Celiac plexus neurolysis

16

0

16

 Exploration alone

26

4

22

PD pancreaticoduodenectomy, PPPD pylorus-preserving pancreaticoduodenectomy

Comparisons between the patients with metastasis (WM) and patients with no metastasis (NM)

Patients’ demographics and laboratory values at the time of diagnosis are shown in Table 2. The mean age of all patients was 61.7 ± 10.4 years (median 62 years, range 29–87 years), and 64.3% (n = 151) were male. The metastasis group had a younger age (59.4 vs. 62.5 years, p = 0.041) and larger tumor size compared with the NM group (4.2 vs. 3.8 cm, p < 0.001). Additionally, patients in the NM group had a higher ALT level (p = 0.010) and a higher AST level (p = 0.010) when compared with patients in the WM group. Levels of TBil and DBil in the WM group were found to be lower than those in the NM group; however, these differences were not significant (p = 0.057 and 0.085, respectively).

Table 2

Demographic and clinical characteristics of included patients

 

Total

(n = 235)

NM

(n = 173)

WM

(n = 62)

p

Age (years) (mean ± SD)

61.7 ± 10.4

62.5 ± 10.4

59.4 ± 10.0

0.041

Sex, male/female

151/84

105/68

46/16

0.057

Chief complaint

 Pain

150

106

44

0.173

 Without pain

85

67

18

 

 Jaundice

73

61

12

0.200

 Without jaundice

162

112

50

 

 Weight loss

100

70

30

0.279

 Without weight loss

135

103

32

 

Personal history

 Smoking, yes/no

48/187

34/139

14/48

0.624

 Drinking, yes/no

38/197

32/141

6/56

0.106

 Hypertension, yes/no

71/164

51/122

20/42

0.683

 Diabetes, yes/no

36/199

25/148

11/51

0.537

Interval between imaging and surgery, days

6.3 ± 4.8

6.3 ± 4.6

6.2 ± 5.2

0.868

Tumor size on MDCT (cm)

4.2 ± 1.9

3.8 ± 1.6

5.5 ± 2.0

< 0.001

Tumor location

 Head

174

134

40

0.046

 Body or tail

61

39

22

 

Laboratory examinations

 ALT

124.6 ± 173.1

142.2 ± 179.1

75.9 ± 146.1

0.010

 AST

84.3 ± 100.5

94.4 ± 105.0

56.3 ± 81.2

0.010

 TBil

73.9 ± 103.8

81.6 ± 107.6

52.4 ± 89.5

0.057

 DBil

50.3 ± 74.6

55.4 ± 77.2

36.3 ± 65.7

0.085

 ALB

40.0 ± 5.4

40.1 ± 5.4

39.7 ± 5.2

0.686

 AFP

2.9 ± 1.8

2.8 ± 1.4

3.1 ± 2.6

0.293

 CA19–9

385.5 ± 378.8

335.7 ± 350.2

525.2 ± 422.0

< 0.001

 CEA

8.9 ± 20.3

8.1 ± 21.9

11.1 ± 14.7

0.328

Predictive factors for occult distant metastases on exploration

Table 3 summarizes the univariate and multivariate logistic regression analyses of the risk factor for distant metastasis using the significant univariate predictors. In univariate analyses, significant predictive factors for finding distant metastasis during surgery were younger age (p = 0.003), larger tumor size (p < 0.001), tumor location (p = 0.048), lower ALT level (p < 0.001), lower AST level (p = 0.006), lower TBil level (p < 0.019), higher CA199 level (p = 0.007), and higher CEA level (p < 0.001) (Table 3). In multivariate analysis, the following variables remained significantly associated with presence of distant metastasis: an age < 62 years old (Odds ratio (OR) = 3.97; 95% Confidence interval (CI): 1.87–8.42; p < 0.001), male sex (OR = 2.79, 95% CI: 1.26–6.19; p = 0.011), a tumor size ≥4.0 cm (OR = 16.02, 95% CI: 5.31–48.30; p < 0.001), ALT level < 125 U/L (OR = 6.19, 95% CI: 2.26–16.92, p < 0.001), and a CA19–9 level ≥ 385 U/ml (OR = 3.53, 95% CI: 1.87–6.67; p < 0.001) (Table 3).
Table 3

Univariate and multivariate analyses of factors predicting distant metastases

  

Total

n = 235

NM

n = 173

WM

n = 62

Univariate analysis

Multivariate analysisa

p

OR (95% CI)

p

OR (95% CI)

Age

> 62

115

95

20

0.003

1

< 0.001

1

 

≤62

120

78

42

 

2.55 (1.39, 4.71)

 

3.97 (1.87, 8.42)

Sex

Female

84

68

16

0.057

1

0.011

1

 

Male

151

105

46

 

1.86 (0.98, 3.55)

 

2.79 (1.26, 6.19)

Pain

No

85

67

18

0.174

1

  
 

Yes

150

106

44

 

1.50 (0.82, 2.90)

  

Jaundice

No

162

112

50

0.022

1

  
 

Yes

73

61

12

 

0.44 (0.22, 0.89)

  

Weight loss

No

135

103

32

0.280

1

  
 

Yes

100

70

30

 

1.37 (0.77, 2.47)

  

Smoking

No

187

139

48

0.624

1

  
 

Yes

48

34

14

 

1.19 (0.59, 2.41)

  

Drinking

No

197

141

56

0.112

1

  
 

Yes

38

32

6

 

0.47 (0.19, 1.19)

  

Hypertension

No

71

51

20

0.683

1

  
 

Yes

164

122

42

 

1.14 (0.61, 2.13)

  

Diabetes

No

199

148

51

0.538

1

  
 

Yes

36

25

11

 

1.28 (0.59, 2.78)

  

Interval between imaging and surgery

≤7

170

123

47

 

1

  

7–14

48

39

9

0.213

0.60 (0.27, 1.34)

  

≥14

17

11

6

0.461

1.49 (0.52, 4.31)

  

Tumor size

< 4.0

96

92

4

< 0.001

1

< 0.001

1

 

≥4.0

139

81

58

 

16.47 (5.73, 47.36)

 

16.02 (5.31, 48.30)

Tumor location

Head

174

134

40

0.048

1

  
 

Body/tail

61

39

22

 

1.88 (1.01, 3.55)

  

ALT

≥125

71

64

7

< 0.001

1

< 0.001

1

 

< 125

164

109

55

 

4.61 (1.98, 10.74)

 

6.19 (2.26, 16.92)

AST

≥ 85

75

64

11

0.006

1

  
 

< 85

160

109

51

 

2.72 (1.32, 5.60)

  

TBil

≥75

78

65

13

0.019

1

  
 

< 75

157

108

49

 

2.27 (1.14, 4.50)

  

DBil

≥50

75

61

14

0.069

1

  
 

< 50

160

112

48

 

1.87 (0.95, 3.66)

  

ALB

≥40

124

89

35

0.498

1

  
 

< 40

111

84

27

 

0.82 (0.46, 1.47)

  

AFP

< 3.0

153

111

42

0.612

1

  
 

≥3.0

82

62

20

 

0.85 (0.46, 1.57)

  

CA19–9

< 385

144

115

29

0.007

1

0.015

1

 

≥385

91

58

33

 

2.26 (1.25, 4.07)

 

2.49 (1.19, 5.21)

CEA

< 9

183

145

38

< 0.001

1

  
 

≥9

52

28

24

 

3.53 (1.87, 6.67)

  

NM, No metastases; WM, with metastases

aA multivariable model was constructed by a backward stepwise method

The five independent risk factors found in the multivariate analysis were used to develop a score system based on the regression coefficient of the multivariate logistic regression model (Table 4). The score values for individual patient ranged from 0 to 8. The risk of patients with distant metastasis progressively increased as the score increased (Table 5, Fig. 2a). A receiver operating characteristic curve of the model showed that the area under curve of this score was 0.85 (95% CI: 0.80–0.89) (Fig. 2b). A score of 6 points was suggested to be the optimal cut-off value (Youden index = 0.548) to divide the risk strata with a sensitivity of 85% and a specificity of 69%.
Table 4

Predictive scoring system for pancreatic fistula

Preoperative factor

β coefficient

Points contributed

Age

 > 62 years old

 

0 point

 ≤ 62 years old

1.38

1 point

Sex

 Female

 

0 point

 Male

1.02

1 point

Tumor size

 < 4.0 cm

 

0 point

 ≥ 4.0 cm

2.78

3 points

ALT

 ≥ 125 U/L

 

0 point

 < 125 U/L

1.89

2 points

CA19–9

 < 385 U/mL

 

0 point

 ≥ 385 U/mL

0.91

1 point

Table 5

Risk of distant metastasis for patients with each score

Score

No. of patients

%

 

Total

WM

Sensitivity (%)

Specificity (%)

Accuracy (%)

Youden Index (%)

0

5

0

0

100

0

26.38

0

1

17

0

0

100

2.89

28.51

2.89

2

20

0

0

100

12.72

35.74

12.72

3

26

1

3.85

100

24.28

44.26

24.28

4

38

4

10.53

98.39

38.73

54.47

37.12

5

23

4

17.39

91.94

58.38

67.23

50.32

6

51

16

31.37

85.48

69.36

73.62

54.84

7

41

26

63.41

59.68

89.60

81.70

49.28

8

14

11

78.57

17.74

98.27

77.02

16.01

Fig. 2
Fig. 2

Prediction of distant metastasis. a Proportion of patients with occult metastasis during laparotomy. b Receiver operating characteristics of number of factors to predict the risk for distant metastasis found at operation

Discussion

Currently, radical resection provides the only chance for long-term survival for patients with PDAC. As surgical skills and perioperative management developed, mortality after pancreatic surgery has dramatically decreased to less than 5% [17]. However, morbidity after pancreatic surgery is still very high. Non-curative exploratory laparotomy of pancreas can have a morbidity as high as 42.3% and does not increase survival [18]. Moreover, this unnecessary operation can postpone other more suitable therapies such as chemotherapy and can become the last straw to their debilitating state.

Unfortunately, not all patients with PDAC who undergo resection surgery can be resected successfully. Despite thorough pre-operative staging with advanced imaging techniques, incidental occult distant metastasis from PDAC is commonly encountered in during surgery [19]. Previous studies revealed that up to 31% of patients with resectable PDAC staged by MDCT were found to have metastases in sbusequent laparotomy or staging laparoscopy [8, 2022]. In patients with locally advanced PDAC, the likelihood of finding unresectable PDAC at operation is much higher [23].

Despite the emerging use of magnetic resonance imaging, endoscopic ultrasound, and positron emission tomography/computed tomography, MDCT remains the most commonly used imaging modality for the diagnosis and staging of PDAC [7, 24, 25]. However, small distant metastases, such as minimal peritoneal deposits and small liver metastases, can remain undetected even with modern computed tomography protocols [26]. Previous studies suggested that patients with PDAC should undergo the operation within 25 or 32 days of diagnostic imaging to reduce the risk of tumor progression to unresectable disease [27, 28]. In the present study, we found that 26% of the patients selected for curative surgery for PDAC had distant metastasis. However, in our study, we found no affects attributable to the time interval between MDCT study and surgery on the accuracy of MDCT in determining the presence or absence of metastatic disease.

Due to the limitation of imaging, other techniques were reported in literature for determining the resectability of PDAC. One such technique is peritoneal lavage cytology (PLC), which is a routinely applied in the diagnosis and staging of several cancers. However, in PDAC, although a positive PLC represents an early recurrence and a worse prognosis, a positive PLC is not regarded as equal to a macrometastasis in patients with PDAC and it does not exclude a curative resection in patients without other distant metastasis [2931]. Another technique is staging laparoscopy, which has been used to diagnose occult metastasis to decrease the number of unnecessary laparotomies in PDAC [3234]. Patients who were found to harbor distant metastasis by laparoscopy staging received palliative chemotherapy earlier and lived longer than patients who underwent only laparotomy [33]. Moreover, a cost analysis indicated that use of laparoscopy in pancreatic cancer did not significantly increase the overall expense of treatment [34]. A recent review of 1146 patients found that diagnostic laparoscopy prior to laparotomy could decrease the rate of unnecessary laparotomy from 40 to 20% in patients with periampullary cancer [10]. As a minimally invasive modality, staging laparoscopy was suggested to be routinely used to identify radiographically occult metastases and prevent rewardless laparotomies [20, 21, 35, 36]. However, as the proportion of patients found to have metastases at laparoscopy is decreasing, its routine use is challenged, and some studies have investigated the indications for selective use of staging laparoscopy in pancreatic cancer [37]. Identifying patients at an increased risk of distant metastasis seems to be a more reasonable approach, that can increase the diagnostic accuracy of staging laparoscopy and deliver optimal disease management.

By comparing a number of preoperative factors, this study identified that young age, male sex, low ALT level, large tumor size, and high CA 19–9 level were independent predictors of distant metastases in patients with resectable PDAC. Previous studies found that tumors in the pancreas body and tail, tumor size as determined by MDCT, serum CA 19–9 level, CEA, and weight loss were risk factors for unresectability in patients with potentially resectable PDAC [20, 3841]. Our study confirmed that tumor in the body and tail, and high CEA were associated with distant metastasis in univariate analysis, but not in multivariate analysis. Weight loss was not associated with distant metastasis. In line with previous studies, CA19–9 and tumor size were independent predictive factors for distant metastasis [37]. Ong et al. found that age < =65 was a predictive factor of resectable disease [42]. On the contrary, our study found that age < =62 was an independent risk factor of distant metastasis. Also, we found that patients with distant metastatic PDAC had significantly lower levels of ALT and AST than patients without distant metastatic PDAC, which might be explained by the following reasons. First, this might be relevant to the population characteristics in our study. For example, all our patients underwent upfront surgery without neoadjuvant chemotherapy, which has liver toxicity and results in elevated levels of ALT and AST. Second, we found that patients with lower ALT levels are more likely to be without jaundice, which, on the one hand is beneficial for liver function, but on the other hand may lead to late diagnosis of PDAC due to lack of symptoms. Third, we found that patients with peritoneal metastases had a slightly lower ALT level than patients with liver metastasis (52.7 ± 139.1 vs 99.2 ± 151.3 U/L, p = 0.212). This implies that liver metastasis could only slightly raise the level of ALT when there are no other contributing factors.

After identifying the risk factors associated with distant metastasis, this study developed a model for predicting occult distant metastasis in patients undergoing non-curative laparotomy for potentially resectable PDAC. When a score of 6 points was taken as the cut-off value, this score system had a sensitivity of 85% and a specificity of 69%. However, it is necessary to point out that the reliability and effectiveness of this score system still needs validation by further studies. Also, because successful resection is the only cure for PDAC, these preoperative predictors alone are not contraindications for pancreatic exploration. The predictive factors identified in this study only indicated that additional preoperative staging modalities, such as selective staging laparoscopy, may be needed before laparotomy is indicated.

This study has several limitations. First, due to the nature of its retrospective design, there was a potential for several biases. For example, small intrahepatic lesions may be missed by palpation. Second, the sample size of the present study is relatively small. Therefore, a well-designed, prospective study with more data will be needed to validate the results of this study. Third, though staging laparoscopy was discussed and suggested in this study, we had limited experience in using it. Lastly, although neoadjuvant therapy has become increasingly common in the practice, our findings may not apply to this group of patients.

Conclusions

In conclusion, we showed that for patients with potentially resectable PDAC based on MDCT, distant metastasis is still frequently encountered during surgery. Younger age, male sex, large tumor size, lower ALT and higher CA19–9 are independent predictive factors for finding distant metastasis during exploration.

Notes

Abbreviations

ALT: 

Alanine aminotransferase

AST: 

Aspartate aminotransferase

CA19–9: 

Carbohydrate antigen

CEA: 

Carcinoembryonic antigen

DBil: 

Direct bilirubin

MDCT: 

Multidetector computed tomography

NM: 

No metastasis

PDAC: 

Pancreatic ductal adenocarcinoma

PLC: 

Periton eal lavage cytology

TBil: 

Total bilirubin

WM: 

With metastasis

Declarations

Acknowledgements

Not applicable

Funding

This work was supported by the Natural Science Foundation of China (81672449); Natural Science Foundation of Jiangsu Province (BK20161590); and the International Exchange and Cooperation Projects of Nanjing Medical University (C046). The founding resources had no role in study design, data collection and analysis, preparation of the manuscript, or decision to publish.

Availability of data and materials

All data in our study are available from the corresponding authors upon reasonable request.

Authors’ contributions

Study conception and design of the study: XL, JuW, WG, KJ, YM, and JiW. Acquisition of data: YF, and QC. Statistical analysis and interpretation of data: XL and YF. Drafting of the manuscript: XL, and JiW. Critical revision: YF, QC, JuW, WG, KJ, and YM. Approval of the final version: all authors.

Ethics approval and consent to participate

This study was approved by the institutional review board at The First Affiliated Hospital of Nanjing Medical University (No. 2016-SR-210). Due to the retrospective nature of this study and all data was retrieved from medical records without additional blood samples or biochemical analysis, informed consent from individual participants was waived.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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Authors’ Affiliations

(1)
Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China
(2)
Pancreas Institute, Nanjing Medical University, Nanjing, China
(3)
Department of Gastrointestinal Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, China

References

  1. Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D, Nones K, Quek K, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518(7540):495–501.View ArticleGoogle Scholar
  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.View ArticleGoogle Scholar
  3. Perysinakis I, Avlonitis S, Georgiadou D, Tsipras H, Margaris I. Five-year actual survival after pancreatoduodenectomy for pancreatic head cancer. ANZ J Surg. 2015;85(3):183–6.View ArticleGoogle Scholar
  4. Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, Gullerud RE, Donohue JH, Nagorney DM, Farnell MB. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247(3):456–62.View ArticleGoogle Scholar
  5. 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):1–7.Google Scholar
  6. Speer AG, Thursfield VJ, Torn-Broers Y, Jefford M. Pancreatic cancer: surgical management and outcomes after 6 years of follow-up. Med J Aust. 2012;196(8):511–5.View ArticleGoogle Scholar
  7. Pietryga JA, Morgan DE. Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol. 2015;6(4):343–57.PubMedPubMed CentralGoogle Scholar
  8. Loizou L, Albiin N, Leidner B, Axelsson E, Fischer MA, Grigoriadis A, Del Chiaro M, Segersvärd R, Verbeke C, Sundin A, Kartalis N. Multidetector CT of pancreatic ductal adenocarcinoma: Effect of tube voltage and iodine load on tumour conspicuity and image quality. Eur Radiol. 2016;26(11):4021-4029.View ArticleGoogle Scholar
  9. Vargas R, Nino-Murcia M, Trueblood W, Jeffrey RB Jr. MDCT in pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR Am J Roentgenol. 2004;182(2):419–25.View ArticleGoogle Scholar
  10. Allen VB, Gurusamy KS, Takwoingi Y, Kalia A, Davidson BR. Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev. 2016;7:CD009323.PubMedGoogle Scholar
  11. Durczynski A, Kumor A, Hogendorf P, Szymanski D, Grzelak P, Strzelczyk J. Preoperative high level of D-dimers predicts unresectability of pancreatic head cancer. World J Gastroenterol. 2014;20(36):13167–71.View ArticleGoogle Scholar
  12. Schlieman MG, Ho HS, Bold RJ. Utility of tumor markers in determining resectability of pancreatic cancer. Arch Surg. 2003;138(9):951–5 discussion 955-956.View ArticleGoogle Scholar
  13. Ellsmere J, Mortele K, Sahani D, Maher M, Cantisani V, Wells W, Brooks D, Rattner D. Does multidetector-row CT eliminate the role of diagnostic laparoscopy in assessing the resectability of pancreatic head adenocarcinoma? Surg Endosc. 2005;19(3):369–73.View ArticleGoogle Scholar
  14. Gleisner AL, Assumpcao L, Cameron JL, Wolfgang CL, Choti MA, Herman JM, Schulick RD, Pawlik TM. Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer. 2007;110(11):2484–92.View ArticleGoogle Scholar
  15. Hackert T, Niesen W, Hinz U, Tjaden C, Strobel O, Ulrich A, Michalski CW, Buchler MW. Radical surgery of oligometastatic pancreatic cancer. Eur J Surg Oncol. 2016;43(2):358–363.View ArticleGoogle Scholar
  16. Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, Ko CY, Bentrem DJ. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–7.View ArticleGoogle Scholar
  17. Gastinger I, Meyer F, Shardin A, Ptok H, Lippert H, Dralle H. Investigations on in-hospital mortality in pancreatic surgery: results of a multicenter observational study. Chirurg. 2018. https://doi.org/10.1007/s00104-018-0654-x.
  18. Insulander J, Sanjeevi S, Haghighi M, Ivanics T, Analatos A, Lundell L, Del Chiaro M, Andren-Sandberg A, Ansorge C. Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma. Br J Surg. 2016;103(9):1200–8.View ArticleGoogle Scholar
  19. Stefanidis D, Grove KD, Schwesinger WH, Thomas CR Jr. The current role of staging laparoscopy for adenocarcinoma of the pancreas: a review. Ann Oncol. 2006;17(2):189–99.View ArticleGoogle Scholar
  20. Contreras CM, Stanelle EJ, Mansour J, Hinshaw JL, Rikkers LF, Rettammel R, Mahvi DM, Cho CS, Weber SM. Staging laparoscopy enhances the detection of occult metastases in patients with pancreatic adenocarcinoma. J Surg Oncol. 2009;100(8):663–9.View ArticleGoogle Scholar
  21. Jimenez RE, Warshaw AL, Rattner DW, Willett CG, McGrath D, Fernandez-del Castillo C. Impact of laparoscopic staging in the treatment of pancreatic cancer. Arch Surg. 2000;135(4):409–14 discussion 414-405.View ArticleGoogle Scholar
  22. Glant JA, Waters JA, House MG, Zyromski NJ, Nakeeb A, Pitt HA, Lillemoe KD, Schmidt CM. Does the interval from imaging to operation affect the rate of unanticipated metastasis encountered during operation for pancreatic adenocarcinoma? Surgery. 2011;150(4):607–14.View ArticleGoogle Scholar
  23. Karabicak I, Satoi S, Yanagimoto H, Yamamoto T, Hirooka S, Yamaki S, Kosaka H, Inoue K, Matsui Y, Kon M. Risk factors for latent distant organ metastasis detected by staging laparoscopy in patients with radiologically defined locally advanced pancreatic ductal adenocarcinoma. J Hepatobiliary Pancreat Sci. 2016;​23(12):750–755.View ArticleGoogle Scholar
  24. Feldman MK, Gandhi NS. Imaging evaluation of pancreatic Cancer. Surg Clin North Am. 2016;96(6):1235–56.View ArticleGoogle Scholar
  25. Tamburrino D, Riviere D, Yaghoobi M, Davidson BR, Gurusamy KS. Diagnostic accuracy of different imaging modalities following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. The Cochrane database of systematic reviews. 2016;9:CD011515.PubMedGoogle Scholar
  26. Lavy R, Gatot I, Markon I, Shapira Z, Chikman B, Copel L, Halevy A. The role of diagnostic laparoscopy in detecting minimal peritoneal metastatic deposits in patients with pancreatic cancer scheduled for curative resection. Surgical laparoscopy, endoscopy & percutaneous techniques. 2012;22(4):358–60.View ArticleGoogle Scholar
  27. Sanjeevi S, Ivanics T, Lundell L, Kartalis N, Andren-Sandberg A, Blomberg J, Del Chiaro M, Ansorge C. Impact of delay between imaging and treatment in patients with potentially curable pancreatic cancer. Br J Surg. 2016;103(3):267–75.View ArticleGoogle Scholar
  28. Raman SP, Reddy S, Weiss MJ, Manos LL, Cameron JL, Zheng L, Herman JM, Hruban RH, Fishman EK, Wolfgang CL. Impact of the time interval between MDCT imaging and surgery on the accuracy of identifying metastatic disease in patients with pancreatic cancer. AJR Am J Roentgenol. 2015;204(1):W37–42.View ArticleGoogle Scholar
  29. Steen W, Blom R, Busch O, Gerhards M, Besselink M, Dijk F, Festen S. Prognostic value of occult tumor cells obtained by peritoneal lavage in patients with resectable pancreatic cancer and no ascites: a systematic review. J Surg Oncol. 2016;114(6):743–51.View ArticleGoogle Scholar
  30. Yamada S, Fujii T, Kanda M, Sugimoto H, Nomoto S, Takeda S, Nakao A, Kodera Y. Value of peritoneal cytology in potentially resectable pancreatic cancer. Br J Surg. 2013;100(13):1791–6.View ArticleGoogle Scholar
  31. Yoshioka R, Saiura A, Koga R, Arita J, Takemura N, Ono Y, Yamamoto J, Yamaguchi T. The implications of positive peritoneal lavage cytology in potentially resectable pancreatic cancer. World J Surg. 2012;36(9):2187–91.View ArticleGoogle Scholar
  32. Ta R, O'Connor DB, Sulistijo A, Chung B, Conlon KC. The role of staging laparoscopy in Resectable and borderline Resectable pancreatic Cancer: a systematic review and meta-analysis. Dig Surg. 2018. https://doi.org/10.1159/000488372.
  33. Sell NM, Fong ZV, Del Castillo CF, Qadan M, Warshaw AL, Chang D, Lillemoe KD, Ferrone CR. Staging laparoscopy not only saves patients an incision, but may also help them live longer. Ann Surg Oncol. 2018;25(4):1009–16.View ArticleGoogle Scholar
  34. Enestvedt CK, Mayo SC, Diggs BS, Mori M, Austin DA, Shipley DK, Sheppard BC, Billingsley KG. Diagnostic laparoscopy for patients with potentially resectable pancreatic adenocarcinoma: is it cost-effective in the current era? J Gastrointest Surg. 2008;12(7):1177–84.View ArticleGoogle Scholar
  35. Hennig R, Tempia-Caliera AA, Hartel M, Buchler MW, Friess H. Staging laparoscopy and its indications in pancreatic cancer patients. Dig Surg. 2002;19(6):484–8.View ArticleGoogle Scholar
  36. Warshaw AL, Tepper JE, Shipley WU. Laparoscopy in the staging and planning of therapy for pancreatic cancer. Am J Surg. 1986;151(1):76–80.View ArticleGoogle Scholar
  37. De Rosa A, Cameron IC, Gomez D. Indications for staging laparoscopy in pancreatic cancer. HPB. 2016;18(1):13–20.View ArticleGoogle Scholar
  38. Maithel SK, Maloney S, Winston C, Gonen M, D'Angelica MI, Dematteo RP, Jarnagin WR, Brennan MF, Allen PJ. Preoperative CA 19-9 and the yield of staging laparoscopy in patients with radiographically resectable pancreatic adenocarcinoma. Ann Surg Oncol. 2008;15(12):3512–20.View ArticleGoogle Scholar
  39. Slaar A, Eshuis WJ, van der Gaag NA, Nio CY, Busch OR, van Gulik TM, Reitsma JB, Gouma DJ. Predicting distant metastasis in patients with suspected pancreatic and periampullary tumors for selective use of staging laparoscopy. World J Surg. 2011;35(11):2528–34.View ArticleGoogle Scholar
  40. Okada K, Kawai M, Tani M, Hirono S, Miyazawa M, Shimizu A, Kitahata Y, Yamaue H. Predicting factors for unresectability in patients with pancreatic ductal adenocarcinoma. J Hepatobiliary Pancreatic Sci. 2014;21(9):648–53.View ArticleGoogle Scholar
  41. Kim YC, Kim HJ, Park JH, Park DI, Cho YK, Sohn CI, Jeon WK, Kim BI, Shin JH. Can preoperative CA19-9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma? J Gastroenterol Hepatol. 2009;24(12):1869–75.View ArticleGoogle Scholar
  42. Ong SL, Garcea G, Thomasset SC, Mann CD, Neal CP, Abu Amara M, Dennison AR, Berry DP. Surrogate markers of resectability in patients undergoing exploration of potentially resectable pancreatic adenocarcinoma. J Gastrointest Surg. 2008;12(6):1068–73.View ArticleGoogle Scholar

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