Efficacy of CT value along portal vein for preoperative prediction of portal vein resection in pancreatic head cancer

doi:10.21203/rs.3.rs-1523367/v1

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Efficacy of CT value along portal vein for preoperative prediction of portal vein resection in pancreatic head cancer

https://doi.org/10.21203/rs.3.rs-1523367/v1

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Background

It is important for surgeons to determine whether combined portal vein (PV) resection (PVR) is necessary before surgery, because the PVR is required in many cases with pancreatic head cancer. The present study aimed to determine the ability of computed tomography (CT) value along the PV in predicting the necessity for concomitant PVR in pancreatic head carcinoma.

Methods

Total 107 consecutive patients who underwent pancreaticoduodenectomy (PD) for invasive ductal carcinoma of the pancreatic head at our institute between September 2007 and September 2020 were reviewed retrospectively. Univariate analysis to predict PVR were performed with preoperative radiological valuables acquired by Synapse Vincent, in addition to clinicopathological factors. The resected specimen near the PV or the PV notch was analyzed by histopathological findings.

Results

Only the CT value of the PV was independently associated with PVR (Mann–Whitney U test; p = 0.045, logistic regression test; p = 0.039). The AUC of the CT value of the PV for the prediction of PVR was 0.616. The outer boundary of the PV was unclear in the cases without pathological PV invasion and PVR due to the development of smooth muscle in the outer membrane of the PV and the proliferation of collagen fibers. The elastic fibers were arranged regularly in the notch portion of the PV in cases wherein PVR was not performed.

Conclusion

The CT value along the PV was independently associated with PVR, and the only predictor of PVR.

Pancreaticoduodenectomy

Portal vein resection

The prognosis of pancreatic cancer is extremely poor. Even after curative resection, the 5-year survival rate is 12–17% [1–3]. A reason for the poor survival rate is that above 50% of the cases are diagnosed at an advanced stage. Peripancreatic vascular invasion, which has a major impact on prognosis, is an important criterion to consider while assessing resectability [4]. For patients with peripancreatic venous involvement, pancreaticoduodenectomy (PD) with portal vein (PV) resection and reconstruction substantially increases the probability of achieving R0 resection [5]. Therefore, accurate preoperative evaluation of the presence of vein invasion is essential [6, 7].

Several models have been proposed for predicting preoperative peripancreatic venous invasion. However, in actual surgery, combined resection of the PV is required in many cases because it cannot be safely detached otherwise. This is true for not only the invasion of cancer but also the effects of concomitant pancreatitis and fibrotic changes around the pancreas. According to recent reports, concomitant PV resection (PVR) during PD in high-volume centers is safe, with lower morbidity and mortality rates than earlier [8]. Therefore, it is important for surgeons to diagnose PV invasion and determine whether combined resection of the PV is necessary before surgery.

The present study aimed to determine the ability of computed tomography (CT) value along the PV in predicting the necessity for concomitant PVR in pancreatic head carcinoma.

Patients

In total, the data of 107 consecutive patients who underwent PD for invasive ductal carcinoma of the pancreatic head at our institute from September 2007 to September 2020 was colected retrospectively. Five patients were excluded from the study, and data from the remaining 102 patients were evaluated. Patients with the following histological tumor types were excluded from the study: mucinous cystadenocarcinoma, intraductal papillary adenocarcinoma, and neuroendocrine carcinoma [7].

Radiological analysis

All patients underwent preoperative abdominal CT during the arterial-phase, portal-phase, and equilibrium phases using Aquilion One (Toshiba Medical Systems, Tokyo, Japan), a LightSpeed Volumetric CT (GE, Waukesha, WI, USA), and Revolution Frontier (GE, Waukesha, WI, USA) reconstructed at 1.25-mm intervals [7]. Unenhanced and three-phase contrast-enhanced helical CT images were obtained. The beginning of image acquisition for each phase after the injection of the contrast material was timed using the automated Dual Shot GX7 (Nemoto Kyorindo, Tokyo, Japan). Arterial phase and portal venous phase image acquisition started at 10 and 40 s after contrast injection, respectively [7]. Delayed-phase image acquisition started 110 s after the contrast injection. Contrast material (mean, 520 mg iodine/kg body weight) was delivered over a period of 30 s [7].

Calculation of CT value along PV by Synapse Vincent

All CT data were analyzed using the Synapse Vincent system (Fuji Film). Images were developed using multiplanar reformation (Fig. 1A). Next, we confirmed the most accessible part of the cancer centering on the PV and confirmed the axial image (Fig. 1A, left upper panel). We then made fine adjustments in the sagittal image (Fig. 1A, right upper panel) and coronal image (Fig. 1A, left lower panel) to follow the PV course. Finally, after reconstructing the image of the most approaching part adjusted parallel to the PV (Fig. 1A, right lower panel), the CT value was measured for individual patients so that the part along the PV had an area of approximately 80 mm², in which the PV was not included (Fig. 1B). All evaluations were performed by two investigators (S.O. and N.C., with 8 and 20 years of post-training experience in surgery and CT imaging, respectively), and the average values were adopted.

Surgical procedure

The PV around the pancreas was dissected as much as possible, regardless of whether it was due to cancer invasion or surrounding inflammation. Concomitant resection of the PV was performed when dissection became difficult. The surgery proceeded with monitoring of the pathological findings for the frozen section collected from around the PV. At the location where cancer invasion was observed, concomitant resection was performed immediately. All authors performed the surgery, and the procedures were unified.

Histopathological analysis

The resected specimens were fixed in formalin and embedded in paraffin. For each case, a representative tissue block showing pancreatic ductal carcinoma and the PV was selected. In the cases without PVR, the part of the pancreatic tissue the PV was probably in contact with was selected. Serial 3-µm-thick sections were prepared from the paraffin-embedded tissue blocks and stained with hematoxylin–eosin, Elastica van Gieson, and Azan.

Statistical analysis

All statistical analyses were performed using SPSS (version 24.0; IBM Corp., Armonk, NY, USA). Categorical variables were evaluated using the chi-square test or Fisher’s exact test. Continuous variables were compared using Student’s t-test or the Mann–Whitney U test (for variables with non-normal distribution). All variables were incorporated into a univariate analysis, and only those variables showing statistical significance (P < 0.05) were evaluated by univariate logistic analyses to identify the independent predictive factors for concomitant PVR in patients with pancreatic head cancer. Survival analysis was performed using the Kaplan–Meier method, and the log-rank test was performed for comparison between groups. Receiver operating characteristic curves and the corresponding area under the curve (AUC) were used to assess the performance of the predictive model with the test data.

Patients’ characteristics and survival analysis

Table 1 summarizes patient characteristics, surgical outcomes, and pathological status. In total, 43 patients (42%) underwent concomitant PVR and 15 (18%) had pathological PV invasion. The median CT value of contrast-enhanced PV was 184 HU (range: 165–202), and the median measurement area along the PV was 80 mm² (range: 78–83).

Table 1

Patient characteristics
Characteristic	N = 102
Sex (male/female)	53 (52%) / 49 (48%)
Age (years)	71 (40–84)
Tumor marker CEA (ng/ml) CA19-9 (U/ml)	3.3 (0.7–150.4) 171 (2–12000)
Radiological status Tumor size on CT (mm) PV length of tumor contact on CT (mm) CT value along PV (HU) CT value in contrast-enhanced PV (HU) Measurement area along PV (mm²)	25 (9–49) 14 (0–38) 82 (18–123) 184 (165–202) 80 (78–83)
Neoadjuvant chemotherapy	15 (15%)
Surgical procedure PPPD / PD or SSPPD PV reconstruction Operative time (min) Blood loss (g)	88 (86%) / 14 (14%) 43 (42%) 420 (130–810) 467 (10–2856)
Morbidity and mortality Morbidity (≥ Clavien Dindo grade IIIA) Mortality	24 (24%) 0 (0%)
Pathological status UICC Stage (I/II/III) Lymph node metastasis PV invasion Residual tumor (R0/R1/R2)	25 (25%) / 66 (65%) / 11 (10%) 65 (64%) 18 (18%) 94 (92%) / 8 (8%) / 0 (0%)
PV; portal vein, CEA; Carcinoembryonic antigen, CA19-9; carbohydrate antigen 19 − 9,HU; Hounsfield unit, CT; computed tomography, PPPD; pylorus preserving pancreatoduodenectomy, PD; pancreatoduodenectomy, SSPPD; subtotal stomach-preserving pancreaticoduodenectomy, UICC; Union for International Cancer Control

Table 2 shows the two groups stratified by the presence or absence of concomitant PVR. The CT value along the PV was significantly higher in the PVR (+) group than in the PVR (-) group (p = 0.039). Other variables that were significantly different between the two groups were neoadjuvant chemotherapy (NAC), operative time, blood loss, and Union for International Cancer Control (UICC) stage. These were understandable results because of the many advanced cases in the PVR (+) group.

Table 2

Patient characteristics stratified by portal vein reconstruction
Characteristic	PV resection (+) N = 43	PV resection (-) N = 59	P value
Sex (male/female)	22 / 21	31 / 28	0.890
Age (years)	69 (40–81)	73 (52–84)	0.055
Tumor marker CEA (ng/ml) CA19-9 (U/ml)	3.1 (1.0–20.8) 195 (2–5132)	3.4 (0.7–150.4) 101 (2–12000)	0.427 0.164
Radiological status Tumor size on CT (mm) PV length of tumor contact on CT (mm) CT value along PV (HU) CT value in contrast-enhanced PV (HU) Measurement area along PV (mm²)	25 (10–49) 17 (8–37) 85 (35–123) 179 (165–198) 81 (75–86)	23 (9–43) 14 (5–35) 76 (18–109) 180 (168–202) 80 (72–89)	0.363 0.162 0.039 0.908 0.130
Neoadjuvant chemotherapy	12	3	0.004
Surgical procedure PPPD / PD or SSPPD Operative time (min) Blood loss (g)	38 / 5 450 (193–810) 710 (55–2856)	50 / 9 392 (130–720) 390 (10–1870)	0.576 0.021 0.004
Morbidity and mortality Morbidity (≥ Clavien Dindo grade IIIA) Mortality	9 0	15 0	0.598 -
Pathological status UICC Stage (I/II/III) Lymph node metastasis PV invasion Residual tumor (R0/R1/R2)	7 / 29 / 7 32 15 37 / 6 / 0	18 / 37 / 4 33 0 57 / 2 / 0	0.045 0.058 - 0.874
PV; portal vein, CEA; Carcinoembryonic antigen, CA19-9; carbohydrate antigen 19 − 9, HU; Hounsfield unit, CT; computed tomography, PPPD; pylorus preserving pancreatoduodenectomy, PD; pancreatoduodenectomy, SSPPD; subtotal stomach-preserving pancreaticoduodenectomy, UICC; Union for International Cancer Control

The overall 5-year survival rate in our series was 16.2%, with a median survival of 20.0 months. As previously reported, our series also showed significantly better survival in patients with positive pathological PV invasion than in those with negative results (data not shown). In addition, no significant difference in overall survival in cases without pathological PV invasion was noted between the PVR (+) and PVR (−) groups (Fig. 2).

Predictive factors for PVR

In this series, univariate analysis showed that sex, age, CEA, CA19-9, tumor size on CT, PV length of tumor contact on CT, and CT value along the PV were analyzed to predict PVR (Table 3). Only the CT value along the PV was independently associated with PVR. The CT value along the PV in the PVR (+) group was significantly higher than that in the PVR (−) group (Mann–Whitney U test; p = 0.045, logistic regression test; p = 0.039) (Fig. 3A). The AUC of the CT value along the PV for the prediction of PVR was 0.616 (Fig. 3B).

Table 3

Univariate analysis of risk factors for portal vein reconstruction
Variables	OR	95% CI	P value
Sex (male/female)	1.057	0.481–2.321	0.890
Age (≥ 70 years)	0.438	0.196–1.077	0.054
CEA (≥ 5ng/ml )	0.685	0.276–1.703	0.416
CA19-9 (≥ 65U/ml )	1.397	0.614–3.176	0.426
Tumor size on CT (≥ 20mm)	1.125	0.449–2.819	0.802
PV length of tumor contact on CT (≥ 15mm)	2.124	0.954–4.730	0.065
CT value along PV (≥ 74 HU)	2.812	1.197–6.608	0.018
CEA; Carcinoembryonic antigen, CA19-9; carbohydrate antigen 19 − 9, PV; portal vein, CT; computed tomography, HU; Hounsfield unit

Histopathological analysis

The representative histopathological findings along the PV of cases with positive pathological PV invasion, negative pathological PV invasion, with PVR performed, and without PVR performed are shown in Fig. 4. The outer boundary of the PV without cancer invasion was clear in cases with pathological PV invasion. On the other hand, the outer boundary of the PV was unclear in the cases without pathological PV invasion and PVR due to the development of smooth muscle in the outer membrane of the PV and the proliferation of collagen fibers. The elastic fibers were arranged regularly in the notch portion of the PV in cases wherein PVR was not performed. The fat layer on the outside was not found pathologically.

Preoperative diagnosis of pathological PV invasion is of great significance. However, it is difficult to predict PV invasion based on morphological changes alone [5]. Although many reports have proposed various nomograms to predict PV invasion, they are unclear because of subjective evaluation of the CT images [6]. Only morphological measurements with low subjectivity were examined. Significant factors that can predict pathological PV invasion include tumor diameter, length of tumor–PV contact, PV circumference, and PV wall irregularities [9, 10]. However, in this study, neither tumor diameter nor the length of the tumor–PV contact were significant factors in predicting concomitant PVR. This is because the objective variable was not pathological invasion but the presence or absence of concomitant PVR. In some cases with concomitant PVR, the tumor was not in contact with the PV. However, in many cases, concomitant PVR was not required even if the tumor was in contact with the PV. However, in cases with pathological PV invasion, the tumor was in contact with the PV.

Preoperative diagnosis of clinical non-invasion of the PV does not coincide with the need for concomitant PVR. From the data of this study, 35% (15 of 43 cases) had pathological PV invasion among the cases with concomitant PVR (40–60% in other reports) [8, 11]. In other words, in addition to predicting PV invasion preoperatively, it is also important to diagnose whether preoperative concomitant PVR is necessary. There are various concepts regarding surgical procedures. If PV invasion, i.e., PV stenosis or obstruction, is apparent on the CT image, the detachment of that part of the PV should be minimized, and combined resection should be performed. However, if the PV invasion is not apparent on the CT image but still suspected, detachment of the area around the PV may be needed or combined resection if detachment is deemed difficult. On the other hand, if clinical PV invasion is suspected, some surgeons perform concomitant PVR in every case. Even if PV invasion is not clinically suspected, difficulties in detachment around the PV are encountered due to inflammatory and fibrotic changes in the surrounding areas. Therefore, it is also important to determine whether concomitant PVR is necessary before surgery.

It is clear that positive pathological PV invasion is a clear prognostic factor. In cases without pathological PV invasion, there was no significant difference in the incidence of postoperative complications due to concomitant PVR, and the prognosis did not change. Therefore, our surgical policy was considered acceptable. In addition, the determination of the need for concomitant PVR before surgery could enable appropriate surgery preparation. The rate of unexpected PVR may also decrease. Pathological PV invasion could not be predicted using the CT value of the PV used in this study. In other words, there was no change in the CT value of the PV values in the two groups with and without pathological PV invasion (data not shown).

If a black band on the CT image is visible at the border of the pancreas in the closest part of the tumor along the PV, it is presumed that it is a fat layer and the CT value is lowered accordingly. In such cases, it is not necessary to measure the CT value, and it is determined that PVR may not be necessary. On the other hand, PVR can be considered necessary even when the PV is narrowed or obstructed due to obvious cancer invasion in the absence of such a fat layer. Difficult cases showed no further fat layer or any obvious deformation of the PV. In this case, it is speculated that measuring the CT value of the closest part would enable a meaningful determination of the need for concomitant PVR.

In the histopathological findings of this study, the border outside the PV was unclear in cases without pathological PV invasion and with PVR, and hyperplasia of the collagen fibers was observed. These facts provide evidence to support the previous hypothesis. In addition, the notch of the PV in cases without PVR showed hyperplasia of the elastic fibers; however, the arrangement was well-organized and the presence of any outer fat layer was not observed. The possible reason is that the fat layer disappeared during the process of resection and specimen preparation.

The limitations of this study are that the number of cases was small and it was retrospective in nature. In addition, the subjective element in the measurement of the CT value along the PV has not been completely eliminated. The measurement area along the PV and CT values in contrast-enhanced PV imaging has a small range, which makes it more objective but not perfect. Furthermore, the effects of morphological change on the CT value due to the effect of NAC was not examined.

The CT value along the PV was independently associated with PVR, and the only predictor of PVR. These results were very useful in predicting PVR preoperatively and was histopathologically supportive.

Ethics approval and consent to participate

This research has been approved by Tokyo Medical University Hachioji Medical Center Ethics Committee. And this research has the informed consent to all participates. Human data and human tissue confirm that all experiments were performed in accordance with Declaration of Helsinki.

Consent for publication

This research has the consent for publication to all authos.

Availability of data and materials

The datasets generated and analysed during the current study are not publicly available due to personal data but are available from the first author on reasonable request.

Competing Interests

All authors declare no conflicts of interest.

Funding

This research has no funding.

Author's contributions

Study design: Author N Chiba, and S Kawachi

Acquisition of data: Author S Ochiai

Operation procedures were performed All authors

Analysis and interpretation: Author S Ochiai

Manuscript drafted by Author S Ochiai and N Chiba

Revision: Author S Ochiai, N Chiba and S Kawachi

Acknowledgements.

None

Ueda M, Endo I, Nakashima M, Minami Y, Takeda K, Matsuo K, et al. Prognostic factors after resection of pancreatic cancer. World J Surg. 2009;33:104–10.
Moon HJ, An JY, Heo JS, Choi SH, Joh JW, Kim YI. Predicting survival after surgical resection for pancreatic ductal adenocarcinoma. Pancreas. 2006;32:37–43.
Alexakis N, Halloran C, Raraty M, Ghaneh P, Sutton R, Neoptolemos JP. Current standards of surgery for pancreatic cancer. Br J Surg. 2004;91:1410–27.
Banz VM, Croagh D, Coldham C, et al. Factors influencing outcome in patients undergoing portal vein resection for adenocarcinoma of the pancreas. Eur J Surg Oncol. 2012;38:72–9.
Chun YS, Milestone BN, Watson JC, Cohen SJ, Burtness B, Engstrom PF, et al. Defining venous involvement in borderline resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2832–8.
Klauss M, Mohr A, von TH, et al. A new invasion score for determining the resectability of pancreatic carcinomas with contrast-enhanced multidetector computed tomography. Pancreatology. 2008;8:204–10.
Teramura K, Noji T, Nakamura T, Asano T, Tanaka K, Nakanishi Y, et al. Preoperative diagnosis of portal vein invasion in pancreatic head cancer: appropriate indications for concomitant portal vein resection. J Hepatobiliary Pancreat Sci. 2016;23:643–649.
Murakami Y, Satoi S,Motoi F, ShoM, Kawai M, Matsumoto I, et al. Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma. Br J Surg. 2015;102:837–46.
Li H, ZengMS, Zhou KR, Jin DY, LouWH. Pancreatic adenocarcinoma: signs of vascular invasion determined by multi-detector row CT. Br J Radiol. 2006;79:880–7.
Marinelli T, Filippone A, Tavano F, Fontana A, Pellegrini F, Koninger J, et al.A tumour scorewithmultidetector spiral CT for venous infiltration in pancreatic cancer: influence on borderline resectable. Radiol Med. 2014;119:334–42.
Nakao A, Kanzaki A, Fujii T, Kodera Y, Yamada S, Sugimoto H, et al. Correlation between radiographic classification and pathological grade of portal vein wall invasion in pancreatic head cancer. Ann Surg. 2012;255:103–8.

No competing interests reported.

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Version 1

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You are reading this latest preprint version

Efficacy of CT value along portal vein for preoperative prediction of portal vein resection in pancreatic head cancer

Status:

Version 1

Abstract

Figures

Introduction

Patients And Methods

Patients

Radiological analysis

Calculation of CT value along PV by Synapse Vincent

Surgical procedure

Histopathological analysis

Statistical analysis

Results

Patients’ characteristics and survival analysis

Predictive factors for PVR

Histopathological analysis

Discussion

Conclusions

Declarations

Ethics approval and consent to participate

Consent for publication

Availability of data and materials

Competing Interests

Funding

Author's contributions

Acknowledgements.

References

Additional Declarations

Status:

Version 1