Original article
Portal vein patency after pancreatoduodenectomy for periampullary cancer M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea Correspondence to: Professor S.-W. Kim, Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul 110–744, Korea (e-mail: [email protected]) Background: The fate of the portal vein (PV) after pancreatoduodenectomy, especially its long-term
patency and associated complications, has received little attention. The aim of this study was to explore the long-term patency rate of the PV after pancreatoduodenectomy, focusing on risk factors for PV stenosis/occlusion and associated complications. Methods: Serial CT images of patients who underwent pancreatoduodenectomy for periampullary cancer between January 2000 and June 2012 in a single institution were evaluated for PV stenosis or occlusion. Results: A total of 826 patients were enrolled. The PV stenosis/occlusion rate after pancreatoduodenectomy was 19⋅6 per cent and the 5-year patency rate 69⋅9 per cent. The most frequent cause of PV stenosis/occlusion was local recurrence followed by postoperative change and PV thrombosis. Patients who underwent PV resection had a higher PV stenosis/occlusion rate than those who did not (51 versus 17⋅4 per cent; P < 0⋅001). The 3-year patency rate was highest in patients with cancer of the ampulla of Vater and lowest in patients with pancreatic cancer (91⋅9 versus 55⋅5 per cent respectively; P < 0⋅001). Multivariable analysis showed that risk factors for PV stenosis/occlusion included primary tumour location, chemoradiotherapy and PV resection. PV stenosis or occlusion without disease recurrence was observed in 17⋅3 per cent of the patients. PV resection and grade B or C pancreatic fistula were independent risk factors for PV stenosis/occlusion. Among 162 patients with PV stenosis or occlusion, five (3⋅1 per cent) had fatal recurrent gastrointestinal bleeding. Conclusion: PV stenosis or occlusion is common after pancreatoduodenectomy, particularly if the PV has been resected and/or chemoradiotherapy was given after surgery. Although recurrence is the most frequent cause of PV stenosis/occlusion, this complication is found in a significant proportion of patients without disease recurrence. Paper accepted 22 September 2014 Published online 12 November 2014 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9682
Introduction
Technical improvements have expanded surgical indications for portal vein (PV) resection during pancreatoduodenectomy for periampullary cancers with suspected PV invasion1,2 . PV resection is regarded as safe and feasible, providing important survival benefits to selected groups of patients. However, these studies focused only on short-term perioperative results, and did not evaluate long-term complications such as PV stenosis/occlusion that develop several months to years after surgery3 . Thorough evaluation of the long-term outcomes of PV resection during pancreatoduodenectomy is required to confirm the safety and feasibility of this procedure, especially in view of the improved survival outcomes of patients with periampullary cancer. © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
Patients who do not undergo PV resection during pancreatoduodenectomy are also at risk of PV-related complications, because the PV is the most manipulated structure during pancreatoduodenectomy. Little is known, however, about the fate of the PV after pancreatoduodenectomy, especially its long-term patency and associated complications3 . Unlike acute PV thrombosis or occlusion after liver transplantation, chronic PV stenosis or occlusion after pancreatoduodenectomy is not considered a serious complication. However, long-standing PV stenosis or occlusion can cause portal hypertension, leading to recurrent gastrointestinal bleeding. Owing to poor overall survival, patients with classical adenocarcinoma of the pancreatic head do not have sufficient time to develop complications associated with PV stenosis/occlusion. In contrast, many patients with distal BJS 2015; 102: 77–84
78
common bile duct (CBD) or ampulla of Vater cancer survive for a prolonged period of time. These patients may therefore develop long-term postoperative complications associated with PV stenosis or occlusion. The long-term postoperative changes in the PV after pancreatoduodenectomy have rarely been studied. The aim of the present study was to investigate the long-term patency of the PV after pancreatoduodenectomy with curative intent, either with or without PV resection. Parameters assessed included PV patency rate, risk factors for PV stenosis or occlusion, and the development of serious complications associated with PV stenosis/occlusion. Methods
Consecutive patients undergoing pancreatoduodenectomy with curative intent for periampullary cancer at Seoul National University Hospital in Korea were eligible for inclusion in this retrospective study. Clinicopathological data and radiological images were collected prospectively as electronic medical records. The study was approved by the Institutional Review Board of Seoul National University Hospital, which waived the requirement for informed consent. Preservation of the pylorus was attempted in all patients undergoing pancreatoduodenectomy, unless duodenal ischaemia, duodenal ulcer or duodenal tumour infiltration was present. Child reconstruction with duct-to-mucosa hepaticojejunostomy and duct-to-mucosa pancreatojejunostomy with external drainage were used as the standard reconstruction procedures. Lymph node dissection during pancreatoduodenectomy included the removal of regional lymph nodes on the right side of the coeliac and superior mesenteric arteries. Skeletonization of the PV and hepatic artery was performed, removing all tissue in the hepatoduodenal ligament. Para-aortic lymph node dissection was not performed routinely4 . Where there was suspicion of tumour invasion into the PV, PV resection was performed if there was no evidence of distant metastasis, collateral vessel formation or tumour thrombi. In patients undergoing PV resection, venous resection and reconstruction were performed in accordance with standard vascular techniques5 . The tumour was dissected and the extent of venous invasion determined. The proximal and distal portions of the involved vein were clamped, and en bloc tumour resection with the involved vein was performed. The surgical methods for reconstruction and the conduits used were tailored according to the vein involved and the extent of resection, including a primary end-to-end anastomosis, wedge resection, venoplasty or bovine patch interposition using non-absorbable monofilament suture. © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
Chemoradiation with or without maintenance chemotherapy was administered to all patients except those with a T1 N0 lesion with no residual tumour, those who had poor performance status, and patients who refused adjuvant treatment. External-beam radiation therapy consisted of a total dose of 45 Gy in 25 fractions. Maintenance chemotherapy consisted primarily of 5-fluorouracil or gemcitabine, at the discretion of the medical oncologist6 . PV patency was evaluated by an experienced biliary–pancreatic surgeon blinded to the primary tumour and to whether a PV resection had been performed. PV diameter in all patients was measured on portal venous phase CT images, taken at a thickness of 1⋅5–3 mm. Images were stored and analysed using picture archiving and communication system (PACS) workstations (Maroview; Marotech, Seoul, South Korea). To eliminate the confounding effect of initial PV diameter, the change in PV diameter was calculated as the percentage poststenosis PV diameter compared with preoperative PV diameter. A reduction of more than 50 per cent in PV diameter was considered clinically meaningful7,8 , with the first occurrence of this reduction on serial CT images defined as the time of PV stenosis/occlusion. The degree of PV diameter change was classified as: grade A (0–49 per cent reduction in diameter), grade B (50–74 per cent reduction), grade C (75–99 per cent reduction) or grade D (total occlusion) (Fig. 1). Patients with grades B–D were defined as having clinically relevant PV stenosis/occlusion. Patients with grade migration were classified according to the final degree of stenosis or occlusion, because risk of complications depends on the final status of the patient.
Statistical analysis SPSS® version 19.0 (IBM, Armonk, New York, USA) was used for statistical analysis. Nominal data were compared with χ2 tests. For binary variables, a logistic regression model was used to find significant risk factors and estimate their odds ratios (ORs). PV patency was assessed by the Kaplan–Meier method and compared using the log rank test. Actual patency was calculated relative to the follow-up period, defined as the time interval from surgery to the date of the last CT scan. As all patients were alive at last follow-up, none was censored owing to death or loss to follow-up. Two-sided P < 0⋅050 was considered statistically significant. Variables with P < 0⋅050 after univariable analysis were entered into the multivariable analysis. Results
Between January 2000 and June 2012, 1161 consecutive patients underwent surgical treatment for periampullary www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy
a
Grade B PV stenosis
b
Grade C PV stenosis
c
Grade D PV occlusion
79
Grading of degree of portal vein (PV) stenosis/occlusion: a grade B, 50 per cent stenosis (PV diameter between 16 and 8 mm); b grade C, 75 per cent stenosis (PV diameter between 15 and 3⋅5 mm); c grade D, total occlusion of PV
Fig. 1
cancer at the authors’ institution. Of 934 resections, 876 (93⋅8 per cent) were performed with curative intent. Fifty of these 876 patients were lost to postoperative imaging follow-up, leaving 826 patients for analysis (Table 1, Fig. 2). The degree of PV diameter change was identified as grade A in 664 patients (80⋅4 per cent), grade B in 19 (2⋅3 per cent), grade C in 52 (6⋅3 per cent) and grade D in 91 (11⋅0 per cent).
Early portal vein occlusion
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
Ten patients experienced postoperative PV stenosis/ occlusion within the first month after surgery. All of these patients had pancreatic head cancer. Six had undergone PV segmental resection and three had wedge resection of the PV because of tumour invasion. One patient developed PV stenosis/occlusion even though PV resection had not BJS 2015; 102: 77–84
80
Table 1
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
Overall portal vein patency
Patient characteristics No. of patients* (n = 826)
Mean(s.d.) age (years) Sex ratio (M : F) Location Pancreatic head Distal CBD Ampulla of Vater Operation Whipple PPPD PV resection End-to-end anastomosis Wedge resection Bovine graft interposition AJCC stage Carcinoma in situ I II III IV ISGPF POPF grade A B C Median (range) length of CT follow-up (months)
62⋅6(9⋅5) 498 : 328 289 (35⋅0) 270 (32⋅7) 267 (32⋅3) 239 (28⋅9) 587 (71⋅1) 55 (6⋅7) 39 15 1
After a median CT follow-up of 22⋅9 months, 162 (19⋅6 per cent) of the 826 patients showed PV stenosis/occlusion after pancreatoduodenectomy with curative intent. Overall median PV patency in these patients was 135⋅9 months, and the 5-year PV patency rate was 69⋅9 per cent. The PV patency rate differed significantly according to tumour location (P < 0⋅001) (Fig. 3).
Timing of portal vein stenosis/occlusion
2 (0⋅2) 216 (26⋅2) 588 (71⋅2) 19 (2⋅3) 1 (0⋅1)† 208 (25⋅2) 67 (8⋅1) 28 (3⋅4) 22⋅9 (0⋅1–165⋅8)
*With percentages in parentheses unless indicated otherwise. †The patient had biopsy-proven liver metastasis and chemotherapy was administered. With regression of the tumour, the patient underwent pylorus-preserving pancreatoduodenectomy (PPPD) with curative intent, and final pathology revealed no residual tumour in either the bile duct or liver. CBD, common bile duct; PV, portal vein; AJCC, American Joint Committee on Cancer; ISGPF, International Study Group on Pancreatic Fistula; POPF, postoperative pancreatic fistula.
been performed. No patient developed PV thrombosis; early PV stenosis/occlusion occurred following extrinsic compression of the PV as a consequence of a postoperative fluid collection or haematoma.
The PV stenosis/occlusion rate before 6 months was significantly higher in patients with pancreatic head cancer (22 of 88 patients, 25 per cent) than in those with cancer of the ampulla of Vater (1 of 25, 4 per cent) or distal CBD (3 of 49, 6 per cent) (P = 0⋅003). The rate was also significantly higher in patients who had PV resection than in those who did not: 15 (54 per cent) of 28 patients versus 11 (8⋅2 per cent) of 134 respectively (P < 0⋅001). In contrast, PV stenosis/occlusion rates after 12 months were significantly higher in patients with ampulla of Vater (20 of 25, 80 per cent) or distal CBD (39 of 49, 80 per cent) cancer than in patients with pancreatic head cancer (41 of 88, 47 per cent) (P = 0⋅001), and in patients who did not undergo PV resection (92 of 134, 68⋅7 per cent) compared with those who did (8 of 28, 29 per cent) (P < 0⋅001).
Causes of portal vein stenosis/occlusion Causes of PV stenosis/occlusion were classified into local recurrence around the PV (108 of 162 patients, 66⋅7 per cent), postoperative change without recurrence (28 of 162, 17⋅3 per cent) and PV thrombosis (26 of 162, 16⋅0 per cent) (Fig. 2). As it is difficult to distinguish postoperative
Consecutive pancreatoduodenectomies n = 826
PV resection n = 55
PV stenosis/occlusion n = 162 (19·6%) No PV resection n = 771
88 (30·4%)
Pancreatic head cancer n = 289
49 (18·1%)
Distal CBD cancer n = 270
25 (9·4%)
Ampulla of Vater cancer n = 267
28 (51%)
134 (17·4%) Causes Local recurrence n = 108 Postoperative change n = 28 PV thrombosis n = 26
Fatal recurrent gastrointestinal bleeding n = 5
Summary of long-term portal vein (PV) patency in consecutive patients undergoing pancreatoduodenectomy. CBD, common bile duct
Fig. 2
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy
81
100
100
80
60
40
20
PV patency (%)
PV patency (%)
80
Ampulla of Vater cancer CBD cancer Pancreatic cancer
60
40 No PV resection PV resection 20
0 No. at risk Ampulla of Vater cancer 267 CBD cancer Pancreatic cancer
270 289
12 24 Time after surgery (months)
36
0 225
175
126
198 157
137 76
114 42
Overall portal vein (PV) patency rates after pancreatoduodenectomy for periampullary cancer. CBD, common bile duct. P < 0⋅001 (log rank test)
Fig. 3
granulation tissue from early local recurrence, serial CT images were analysed to the end of follow-up to assess changes in soft tissue density around the PV in conjunction with other evidence of tumour recurrence. Among patients with PV stenosis/occlusion, the median time to PV stenosis/occlusion caused by local recurrence, PV thrombosis and granulation tissue was 15⋅1, 16⋅3 and 16⋅2 months respectively (P = 0⋅814). PV stenosis/occlusion was caused by local recurrence more frequently in patients with pancreatic head cancer (65 of 88, 74 per cent) than in those with ampulla of Vater cancer (11 of 25, 44 per cent), whereas postoperative granulation tissue formation caused PV stenosis/occlusion more frequently in patients with ampulla of Vater (6 of 25, 24 per cent) or distal CBD (11 of 49, 22 per cent) cancer than in those with pancreatic head cancer (11 of 88, 13 per cent) (P = 0⋅042). Postoperative complication rates were higher in patients with PV stenosis/occlusion caused by postoperative granulation tissue formation (21 of 28, 75 per cent) than when caused by local recurrence (44 of 108, 40⋅7 per cent) or PV thrombosis (12 of 26, 46 per cent) (P = 0⋅005). In addition, the occurrence of grade B or C pancreatic fistula was more common with granulation tissue formation (8 of 28, 29 per cent) than with local recurrence (10 of 108, 9⋅3 per cent) or PV thrombosis (3 of 26, 12 per cent) (P = 0⋅011).
Portal vein stenosis/occlusion in relation to portal vein resection Of the 55 patients who underwent PV resection, 28 (51 per cent) developed PV stenosis or occlusion. The © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
12
24
36
Time after surgery (months) No. at risk No PV resection PV resection
771 55
557 24
378 10
277 5
Overall portal vein (PV) patency according to PV resection. P < 0⋅001 (log rank test)
Fig. 4
5-year PV patency rate was significantly lower in patients who had PV resection than in those who did not (17 versus 72⋅7 per cent; P < 0⋅001) (Fig. 4). The method of PV reconstruction was not associated with PV patency: 54 per cent (21 of 39) for end-to-end anastomosis versus 40 per cent (6 of 15) for wedge resection versus 0 per cent (0 of 1) for bovine graft interposition (P = 0⋅210). PV patency rates were compared according to tumour location after stage matching. Of patients with stage II disease, the 3-year PV patency rate was significantly lower for those who had PV resection than in patients who did not, both in the group with distal CBD cancer (50 versus 78⋅9 per cent respectively; P = 0⋅032) and in the group with pancreatic head cancer (33 versus 59⋅8 per cent; P < 0⋅001).
Risk factor analysis for portal vein stenosis/occlusion after curative pancreatoduodenectomy Multivariable analysis showed that tumour location (P < 0⋅001), PV resection (P < 0⋅001) and chemoradiotherapy (P = 0⋅044) were independent risk factors for PV stenosis/occlusion after pancreatoduodenectomy with curative intent (Table 2). For pancreatic head cancer, PV resection (OR 4⋅20, 95 per cent c.i. 2⋅01 to 8⋅78; P < 0⋅001) and tumour recurrence (OR 7⋅81, 2⋅85 to 21⋅39; P < 0⋅001) were independent risk factors for PV stenosis/occlusion. www.bjs.co.uk
BJS 2015; 102: 77–84
82
Table 2
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
Risk factors for portal vein stenosis or occlusion Stenosis or occlusion* No (n = 664)
Co-morbidity Yes No Location Ampulla of Vater Distal CBD Pancreas PV resection Yes No Complication Yes No POPF None or grade A Grade B or C Chemoradiotherapy Yes No
Yes (n = 162)
P‡
Odds ratio†
P§
0⋅481 314 (81⋅6) 350 (79⋅4)
71 (18⋅4) 91 (20⋅6)
242 (90⋅6) 221 (81⋅9) 201 (69⋅6)
25 (9⋅4) 49 (18⋅1) 88 (30⋅4)
27 (49) 637 (82⋅6)
28 (51) 134 (17⋅4)
356 (82⋅2) 308 (78⋅4)
77 (17⋅8) 85 (21⋅6)
589 (80⋅6) 75 (79)
142 (19⋅4) 20 (21)
322 (75⋅1) 306 (86⋅2)
107 (24⋅9) 49 (13⋅8)
< 0⋅001
< 0⋅001 1⋅97 (1⋅15, 3⋅37) 2⋅93 (1⋅74, 4⋅93)
0⋅014 < 0⋅001
3⋅28 (1⋅80, 6⋅00)
< 0⋅001
1⋅51 (1⋅01, 2⋅25)
0⋅044
< 0⋅001
0⋅164
0⋅707
< 0⋅001
Values in parentheses are *percentages and †95 per cent c.i. CBD, common bile duct; PV, portal vein; POPF, postoperative pancreatic fistula. ‡χ2 test; §logistic regression.
Portal vein stenosis/occlusion without evidence of disease recurrence Of the 162 patients with PV stenosis/occlusion, 28 (17⋅3 per cent) developed PV stenosis/occlusion without evidence of disease recurrence. Of these patients, six had ampulla of Vater, 11 had distal CBD and 11 had pancreatic head cancer. Causes of PV stenosis/occlusion were postoperative fluid collection, organized haematomas or granulation tissue formation. Median time to PV stenosis/occlusion was 16⋅3 (range 0⋅1–73⋅5) months. Multivariable analysis showed that postoperative pancreatic fistula formation (OR 3⋅18, 95 per cent c.i. 1⋅08 to 9⋅34; P = 0⋅035) was an independent risk factor for PV stenosis/occlusion in patients without evidence of disease recurrence, and PV resection (OR 4⋅49, 0⋅91 to 22⋅13; P = 0⋅065) had marginal significance.
Rare but fatal complications caused by portal vein stenosis/occlusion Twenty-one (13⋅0 per cent) of the 162 patients with PV stenosis/occlusion developed gastric or hepaticojejunostomy varices; 19 had grade D occlusion (100 per cent) and two had grade C stenosis (75–99 per cent). No patient with grade B stenosis developed varices. Five of these 21 patients showed no evidence of disease recurrence; of these, one had undergone PV resection, and two had grade B and three had grade C pancreatic fistula. Among patients with PV stenosis/occlusion, five developed fatal recurrent gastrointestinal bleeding due to gastric © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
or hepaticojejunostomy varices. Gastrointestinal bleeding developed a median of 16⋅7 (range 12⋅2–36⋅5) months after surgery. All five patients underwent PV stent insertion to lower PV pressure. One also had an explorative laparotomy to control the bleeding, which was unsuccessful. Discussion
PV complications after liver transplantation have been well documented because PV stenosis and thrombosis can be potentially devastating and lead to graft failure9 . Less is known, however, about PV complications after pancreatoduodenectomy. PV stenosis can occur during the immediate perioperative period or may manifest many years after surgery. Most patients are asymptomatic, whereas others present with the typical clinical signs of portal hypertension, including gastrointestinal haemorrhage, ascites and splenomegaly10 . Long-term patency of the PV should be examined, because long-term survivors who experience PV stenosis/occlusion may develop PV hypertension. The present study included a large patient cohort who underwent long-term follow-up of the PV after pancreatoduodenectomy with curative intent. The PV patency rate differed significantly according to the site of the primary tumour, being highest in patients with ampullary cancer and lowest in those with pancreatic head cancer. Multivariable analysis also revealed that primary tumour location was an independent risk factor for PV stenosis/occlusion. Tumour recurrence around the PV was the most frequent cause of PV stenosis/occlusion www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy
83
after pancreatoduodenectomy for periampullary cancer. Thus, pancreatic cancer had the highest risk of PV stenosis/occlusion because its recurrence rate was highest. Moreover, most patients with pancreatic cancer developed PV stenosis/occlusion within 6 months after surgery as a result of early recurrence. In contrast, most patients with ampullary or distal CBD cancers who developed PV stenosis/occlusion did so after 12 months, with the PV change in these patients being due to postoperative formation of granulation tissue rather than disease recurrence. Interestingly, the study found that 17⋅3 per cent of patients with PV stenosis/occlusion had no evidence of disease recurrence. After surgery, granulation tissue developed around the PV in these patients, reducing PV diameter. More than 60 per cent of these patients (17 of 28) did not undergo PV resection, and a higher proportion had ampullary or distal CBD cancer. Patients with grade B or C pancreatic fistula tended to develop PV stenosis/occlusion associated with granulation tissue formation. PV resection has been regarded as affecting PV patency. To date, the complication rates reported after pancreatoduodenectomy combined with PV resection have been found to range from 16⋅7 to 54 per cent11 – 20 . However, these morbidity rates included only short-term perioperative complications such as pancreatic fistula, delayed gastric emptying and intra-abdominal abscess formation. Most previous studies have focused on PV thrombosis rates after PV resection. Thrombosis rates immediately and from 6 months to 3 years after PV resection have been reported to range from 0 to 4 per cent15,21 – 25 and from 0 to 40 per cent5,13,26 – 28 respectively. As shown in the present data, the PV thrombosis rate after PV resection was 0 per cent, and all PV thromboses developed in patients who did not undergo PV resection. In addition, types of venous reconstruction were not related to PV patency. In contrast, in the present series, the rate of PV thrombosis as a cause of PV stenosis/occlusion after pancreatoduodenectomy for periampullary cancer was only 16⋅0 per cent. PV patency rates were significantly lower in patients who had PV resection than in those who did not. In addition, 15 (58 per cent) of 26 patients who developed PV stenosis/occlusion within 6 months after surgery had undergone PV resection. Although PV resection did not increase the PV thrombosis rate, PV resection was related to immediate and long-term PV stenosis/occlusion. Therefore, this procedure is not free from morbidity and candidates for PV resection should be selected carefully. Importantly, 13⋅0 per cent of patients with PV stenosis/occlusion developed gastric or hepaticojejunostomy varices, with five (21 per cent) of these 21 patients experiencing fatal recurrent gastrointestinal bleeding. Careful
postoperative surveillance for PV stenosis/occlusion is required, especially in patients with distal CBD or ampulla of Vater cancer because their overall survival is longer and hence they have increased time to develop these serious complications. Moreover, as even patients who did not undergo PV resection or experience disease recurrence developed these fatal complications, the risk of PV stenosis/occlusion and the occurrence of its associated complications should not be overlooked. Because the incidence of complications related to PV stenting is higher than the rate of gastrointestinal bleeding caused by portal hypertension, routine PV stenting is not recommended in patients with asymptomatic PV occlusion. However, an aggressive approach including PV stenting or selective surgical therapy to lower PV hypertension is needed in patients who develop recurrent gastrointestinal bleeding.
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
Acknowledgements
This study was supported by a grant from the National R&D Programme for Cancer Control funded by the Ministry of Health & Welfare, Republic of Korea (no. 1120310) and Seoul National University (no. 30-2013-0100). Disclosure: The authors declare no conflict of interest. References 1 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: 103–108. 2 Ramacciato G, Mercantini P, Petrucciani N, Giaccaglia V, Nigri G, Ravaioli M et al. Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma? Ann Surg Oncol 2009; 16: 817–825. 3 Chua TC, Saxena A. Extended pancreaticoduodenectomy with vascular resection for pancreatic cancer: a systematic review. J Gastrointest Surg 2010; 14: 1442–1452. 4 Han SS, Jang JY, Kim SW, Kim WH, Lee KU, Park YH. Analysis of long-term survivors after surgical resection for pancreatic cancer. Pancreas 2006; 32: 271–275. 5 Kim SM, Min SK, Park D, Min SI, Jang JY, Kim SW et al. Reconstruction of portal vein and superior mesenteric vein after extensive resection for pancreatic cancer. J Korean Surg Soc 2013; 84: 346–352. 6 Kang MJ, Jang JY, Lee SE, Lim CS, Lee KU, Kim SW. Comparison of the long-term outcomes of uncinate process cancer and non-uncinate process pancreas head cancer: poor prognosis accompanied by early locoregional recurrence. Langenbecks Arch Surg 2010; 395: 697–706. 7 Wei BJ, Zhai RY, Wang JF, Dai DK, Yu P. Percutaneous portal venoplasty and stenting for anastomotic stenosis after
BJS 2015; 102: 77–84
84
8
9
10
11
12
13
14
15
16
17
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
liver transplantation. World J Gastroenterol 2009; 15: 1880–1885. Kim BS, Kim TK, Jung DJ, Kim JH, Bae IY, Sung KB et al. Vascular complications after living related liver transplantation: evaluation with gadolinium-enhanced three-dimensional MR angiography. AJR Am J Roentgenol 2003; 181: 467–474. Woo DH, Laberge JM, Gordon RL, Wilson MW, Kerlan RK Jr. Management of portal venous complications after liver transplantation. Tech Vasc Interv Radiol 2007; 10: 233–239. Settmacher U, Nussler NC, Glanemann M, Haase R, Heise M, Bechstein WO et al. Venous complications after orthotopic liver transplantation. Clin Transplant 2000; 14: 235–241. Howard TJ, Villanustre N, Moore SA, DeWitt J, LeBlanc J, Maglinte D et al. Efficacy of venous reconstruction in patients with adenocarcinoma of the pancreatic head. J Gastrointest Surg 2003; 7: 1089–1095. Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK et al. Pancreaticoduodenectomy with en bloc portal vein resection for pancreatic carcinoma with suspected portal vein involvement. World J Surg 2004; 28: 602–608. Jain S, Sacchi M, Vrachnos P, Lygidakis NJ. Carcinoma of the pancreas with portal vein involvement – our experience with a modified technique of resection. Hepatogastroenterology 2005; 52: 1596–1600. Kurosaki I, Hatakeyama K, Minagawa M, Sato D. Portal vein resection in surgery for cancer of biliary tract and pancreas: special reference to the relationship between the surgical outcome and site of primary tumor. J Gastrointest Surg 2008; 12: 907–918. Capussotti L, Massucco P, Ribero D, Vigano L, Muratore A, Calgaro M. Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes and implications for therapy. Arch Surg 2003; 138: 1316–1322. Riediger H, Makowiec F, Fischer E, Adam U, Hopt UT. Postoperative morbidity and long-term survival after pancreaticoduodenectomy with superior mesentericoportal vein resection. J Gastrointest Surg 2006; 10: 1106–1115. Ouaissi M, Hubert C, Verhelst R, Astarci P, Sempoux C, Jouret-Mourin A et al. Vascular reconstruction during pancreatoduodenectomy for ductal adenocarcinoma of the pancreas improves resectability but does not achieve cure. World J Surg 2010; 34: 2648–2661.
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
18 Turrini O, Ewald J, Barbier L, Mokart D, Blache JL, Delpero JR. Should the portal vein be routinely resected during pancreaticoduodenectomy for adenocarcinoma? Ann Surg 2013; 257: 726–730. 19 Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N et al. Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma. J Surg Oncol 2013; 107: 414–421. 20 Kim PT, Wei AC, Atenafu EG, Cavallucci D, Cleary SP, Moulton CA et al. Planned versus unplanned portal vein resections during pancreaticoduodenectomy for adenocarcinoma. Br J Surg 2013; 100: 1349–1356. 21 Bachellier P, Nakano H, Oussoultzoglou PD, Weber JC, Boudjema K, Wolf PD et al. Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile? Am J Surg 2001; 182: 120–129. 22 Carrère N, Sauvanet A, Goere D, Kianmanesh R, Vullierme MP, Couvelard A et al. Pancreaticoduodenectomy with mesentericoportal vein resection for adenocarcinoma of the pancreatic head. World J Surg 2006; 30: 1526–1535. 23 Wang C, Wu H, Xiong J, Zhou F, Tao J, Liu T et al. Pancreaticoduodenectomy with vascular resection for local advanced pancreatic head cancer: a single center retrospective study. J Gastrointest Surg 2008; 12: 2183–2190. 24 Illuminati G, Carboni F, Lorusso R, D’Urso A, Ceccanei G, Papaspyropoulos V et al. Results of a pancreatectomy with a limited venous resection for pancreatic cancer. Surg Today 2008; 38: 517–523. 25 Yekebas EF, Bogoevski D, Cataldegirmen G, Kunze C, Marx A, Vashist YK et al. En bloc vascular resection for locally advanced pancreatic malignancies infiltrating major blood vessels: perioperative outcome and long-term survival in 136 patients. Ann Surg 2008; 247: 300–309. 26 Smoot RL, Christein JD, Farnell MB. Durability of portal venous reconstruction following resection during pancreaticoduodenectomy. J Gastrointest Surg 2006; 10: 1371–1375. 27 Martin RC II, Scoggins CR, Egnatashvili V, Staley CA, McMasters KM, Kooby DA. Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes. Arch Surg 2009; 144: 154–159. 28 Stauffer JA, Dougherty MK, Kim GP, Nguyen JH. Interposition graft with polytetrafluoroethylene for mesenteric and portal vein reconstruction after pancreaticoduodenectomy. Br J Surg 2009; 96: 247–252.
www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy for periampullary cancer M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea Correspondence to: Professor S.-W. Kim, Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Chongno-gu, Seoul 110–744, Korea (e-mail: [email protected]) Background: The fate of the portal vein (PV) after pancreatoduodenectomy, especially its long-term
patency and associated complications, has received little attention. The aim of this study was to explore the long-term patency rate of the PV after pancreatoduodenectomy, focusing on risk factors for PV stenosis/occlusion and associated complications. Methods: Serial CT images of patients who underwent pancreatoduodenectomy for periampullary cancer between January 2000 and June 2012 in a single institution were evaluated for PV stenosis or occlusion. Results: A total of 826 patients were enrolled. The PV stenosis/occlusion rate after pancreatoduodenectomy was 19⋅6 per cent and the 5-year patency rate 69⋅9 per cent. The most frequent cause of PV stenosis/occlusion was local recurrence followed by postoperative change and PV thrombosis. Patients who underwent PV resection had a higher PV stenosis/occlusion rate than those who did not (51 versus 17⋅4 per cent; P < 0⋅001). The 3-year patency rate was highest in patients with cancer of the ampulla of Vater and lowest in patients with pancreatic cancer (91⋅9 versus 55⋅5 per cent respectively; P < 0⋅001). Multivariable analysis showed that risk factors for PV stenosis/occlusion included primary tumour location, chemoradiotherapy and PV resection. PV stenosis or occlusion without disease recurrence was observed in 17⋅3 per cent of the patients. PV resection and grade B or C pancreatic fistula were independent risk factors for PV stenosis/occlusion. Among 162 patients with PV stenosis or occlusion, five (3⋅1 per cent) had fatal recurrent gastrointestinal bleeding. Conclusion: PV stenosis or occlusion is common after pancreatoduodenectomy, particularly if the PV has been resected and/or chemoradiotherapy was given after surgery. Although recurrence is the most frequent cause of PV stenosis/occlusion, this complication is found in a significant proportion of patients without disease recurrence. Paper accepted 22 September 2014 Published online 12 November 2014 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9682
Introduction
Technical improvements have expanded surgical indications for portal vein (PV) resection during pancreatoduodenectomy for periampullary cancers with suspected PV invasion1,2 . PV resection is regarded as safe and feasible, providing important survival benefits to selected groups of patients. However, these studies focused only on short-term perioperative results, and did not evaluate long-term complications such as PV stenosis/occlusion that develop several months to years after surgery3 . Thorough evaluation of the long-term outcomes of PV resection during pancreatoduodenectomy is required to confirm the safety and feasibility of this procedure, especially in view of the improved survival outcomes of patients with periampullary cancer. © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
Patients who do not undergo PV resection during pancreatoduodenectomy are also at risk of PV-related complications, because the PV is the most manipulated structure during pancreatoduodenectomy. Little is known, however, about the fate of the PV after pancreatoduodenectomy, especially its long-term patency and associated complications3 . Unlike acute PV thrombosis or occlusion after liver transplantation, chronic PV stenosis or occlusion after pancreatoduodenectomy is not considered a serious complication. However, long-standing PV stenosis or occlusion can cause portal hypertension, leading to recurrent gastrointestinal bleeding. Owing to poor overall survival, patients with classical adenocarcinoma of the pancreatic head do not have sufficient time to develop complications associated with PV stenosis/occlusion. In contrast, many patients with distal BJS 2015; 102: 77–84
78
common bile duct (CBD) or ampulla of Vater cancer survive for a prolonged period of time. These patients may therefore develop long-term postoperative complications associated with PV stenosis or occlusion. The long-term postoperative changes in the PV after pancreatoduodenectomy have rarely been studied. The aim of the present study was to investigate the long-term patency of the PV after pancreatoduodenectomy with curative intent, either with or without PV resection. Parameters assessed included PV patency rate, risk factors for PV stenosis or occlusion, and the development of serious complications associated with PV stenosis/occlusion. Methods
Consecutive patients undergoing pancreatoduodenectomy with curative intent for periampullary cancer at Seoul National University Hospital in Korea were eligible for inclusion in this retrospective study. Clinicopathological data and radiological images were collected prospectively as electronic medical records. The study was approved by the Institutional Review Board of Seoul National University Hospital, which waived the requirement for informed consent. Preservation of the pylorus was attempted in all patients undergoing pancreatoduodenectomy, unless duodenal ischaemia, duodenal ulcer or duodenal tumour infiltration was present. Child reconstruction with duct-to-mucosa hepaticojejunostomy and duct-to-mucosa pancreatojejunostomy with external drainage were used as the standard reconstruction procedures. Lymph node dissection during pancreatoduodenectomy included the removal of regional lymph nodes on the right side of the coeliac and superior mesenteric arteries. Skeletonization of the PV and hepatic artery was performed, removing all tissue in the hepatoduodenal ligament. Para-aortic lymph node dissection was not performed routinely4 . Where there was suspicion of tumour invasion into the PV, PV resection was performed if there was no evidence of distant metastasis, collateral vessel formation or tumour thrombi. In patients undergoing PV resection, venous resection and reconstruction were performed in accordance with standard vascular techniques5 . The tumour was dissected and the extent of venous invasion determined. The proximal and distal portions of the involved vein were clamped, and en bloc tumour resection with the involved vein was performed. The surgical methods for reconstruction and the conduits used were tailored according to the vein involved and the extent of resection, including a primary end-to-end anastomosis, wedge resection, venoplasty or bovine patch interposition using non-absorbable monofilament suture. © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
Chemoradiation with or without maintenance chemotherapy was administered to all patients except those with a T1 N0 lesion with no residual tumour, those who had poor performance status, and patients who refused adjuvant treatment. External-beam radiation therapy consisted of a total dose of 45 Gy in 25 fractions. Maintenance chemotherapy consisted primarily of 5-fluorouracil or gemcitabine, at the discretion of the medical oncologist6 . PV patency was evaluated by an experienced biliary–pancreatic surgeon blinded to the primary tumour and to whether a PV resection had been performed. PV diameter in all patients was measured on portal venous phase CT images, taken at a thickness of 1⋅5–3 mm. Images were stored and analysed using picture archiving and communication system (PACS) workstations (Maroview; Marotech, Seoul, South Korea). To eliminate the confounding effect of initial PV diameter, the change in PV diameter was calculated as the percentage poststenosis PV diameter compared with preoperative PV diameter. A reduction of more than 50 per cent in PV diameter was considered clinically meaningful7,8 , with the first occurrence of this reduction on serial CT images defined as the time of PV stenosis/occlusion. The degree of PV diameter change was classified as: grade A (0–49 per cent reduction in diameter), grade B (50–74 per cent reduction), grade C (75–99 per cent reduction) or grade D (total occlusion) (Fig. 1). Patients with grades B–D were defined as having clinically relevant PV stenosis/occlusion. Patients with grade migration were classified according to the final degree of stenosis or occlusion, because risk of complications depends on the final status of the patient.
Statistical analysis SPSS® version 19.0 (IBM, Armonk, New York, USA) was used for statistical analysis. Nominal data were compared with χ2 tests. For binary variables, a logistic regression model was used to find significant risk factors and estimate their odds ratios (ORs). PV patency was assessed by the Kaplan–Meier method and compared using the log rank test. Actual patency was calculated relative to the follow-up period, defined as the time interval from surgery to the date of the last CT scan. As all patients were alive at last follow-up, none was censored owing to death or loss to follow-up. Two-sided P < 0⋅050 was considered statistically significant. Variables with P < 0⋅050 after univariable analysis were entered into the multivariable analysis. Results
Between January 2000 and June 2012, 1161 consecutive patients underwent surgical treatment for periampullary www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy
a
Grade B PV stenosis
b
Grade C PV stenosis
c
Grade D PV occlusion
79
Grading of degree of portal vein (PV) stenosis/occlusion: a grade B, 50 per cent stenosis (PV diameter between 16 and 8 mm); b grade C, 75 per cent stenosis (PV diameter between 15 and 3⋅5 mm); c grade D, total occlusion of PV
Fig. 1
cancer at the authors’ institution. Of 934 resections, 876 (93⋅8 per cent) were performed with curative intent. Fifty of these 876 patients were lost to postoperative imaging follow-up, leaving 826 patients for analysis (Table 1, Fig. 2). The degree of PV diameter change was identified as grade A in 664 patients (80⋅4 per cent), grade B in 19 (2⋅3 per cent), grade C in 52 (6⋅3 per cent) and grade D in 91 (11⋅0 per cent).
Early portal vein occlusion
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
Ten patients experienced postoperative PV stenosis/ occlusion within the first month after surgery. All of these patients had pancreatic head cancer. Six had undergone PV segmental resection and three had wedge resection of the PV because of tumour invasion. One patient developed PV stenosis/occlusion even though PV resection had not BJS 2015; 102: 77–84
80
Table 1
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
Overall portal vein patency
Patient characteristics No. of patients* (n = 826)
Mean(s.d.) age (years) Sex ratio (M : F) Location Pancreatic head Distal CBD Ampulla of Vater Operation Whipple PPPD PV resection End-to-end anastomosis Wedge resection Bovine graft interposition AJCC stage Carcinoma in situ I II III IV ISGPF POPF grade A B C Median (range) length of CT follow-up (months)
62⋅6(9⋅5) 498 : 328 289 (35⋅0) 270 (32⋅7) 267 (32⋅3) 239 (28⋅9) 587 (71⋅1) 55 (6⋅7) 39 15 1
After a median CT follow-up of 22⋅9 months, 162 (19⋅6 per cent) of the 826 patients showed PV stenosis/occlusion after pancreatoduodenectomy with curative intent. Overall median PV patency in these patients was 135⋅9 months, and the 5-year PV patency rate was 69⋅9 per cent. The PV patency rate differed significantly according to tumour location (P < 0⋅001) (Fig. 3).
Timing of portal vein stenosis/occlusion
2 (0⋅2) 216 (26⋅2) 588 (71⋅2) 19 (2⋅3) 1 (0⋅1)† 208 (25⋅2) 67 (8⋅1) 28 (3⋅4) 22⋅9 (0⋅1–165⋅8)
*With percentages in parentheses unless indicated otherwise. †The patient had biopsy-proven liver metastasis and chemotherapy was administered. With regression of the tumour, the patient underwent pylorus-preserving pancreatoduodenectomy (PPPD) with curative intent, and final pathology revealed no residual tumour in either the bile duct or liver. CBD, common bile duct; PV, portal vein; AJCC, American Joint Committee on Cancer; ISGPF, International Study Group on Pancreatic Fistula; POPF, postoperative pancreatic fistula.
been performed. No patient developed PV thrombosis; early PV stenosis/occlusion occurred following extrinsic compression of the PV as a consequence of a postoperative fluid collection or haematoma.
The PV stenosis/occlusion rate before 6 months was significantly higher in patients with pancreatic head cancer (22 of 88 patients, 25 per cent) than in those with cancer of the ampulla of Vater (1 of 25, 4 per cent) or distal CBD (3 of 49, 6 per cent) (P = 0⋅003). The rate was also significantly higher in patients who had PV resection than in those who did not: 15 (54 per cent) of 28 patients versus 11 (8⋅2 per cent) of 134 respectively (P < 0⋅001). In contrast, PV stenosis/occlusion rates after 12 months were significantly higher in patients with ampulla of Vater (20 of 25, 80 per cent) or distal CBD (39 of 49, 80 per cent) cancer than in patients with pancreatic head cancer (41 of 88, 47 per cent) (P = 0⋅001), and in patients who did not undergo PV resection (92 of 134, 68⋅7 per cent) compared with those who did (8 of 28, 29 per cent) (P < 0⋅001).
Causes of portal vein stenosis/occlusion Causes of PV stenosis/occlusion were classified into local recurrence around the PV (108 of 162 patients, 66⋅7 per cent), postoperative change without recurrence (28 of 162, 17⋅3 per cent) and PV thrombosis (26 of 162, 16⋅0 per cent) (Fig. 2). As it is difficult to distinguish postoperative
Consecutive pancreatoduodenectomies n = 826
PV resection n = 55
PV stenosis/occlusion n = 162 (19·6%) No PV resection n = 771
88 (30·4%)
Pancreatic head cancer n = 289
49 (18·1%)
Distal CBD cancer n = 270
25 (9·4%)
Ampulla of Vater cancer n = 267
28 (51%)
134 (17·4%) Causes Local recurrence n = 108 Postoperative change n = 28 PV thrombosis n = 26
Fatal recurrent gastrointestinal bleeding n = 5
Summary of long-term portal vein (PV) patency in consecutive patients undergoing pancreatoduodenectomy. CBD, common bile duct
Fig. 2
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy
81
100
100
80
60
40
20
PV patency (%)
PV patency (%)
80
Ampulla of Vater cancer CBD cancer Pancreatic cancer
60
40 No PV resection PV resection 20
0 No. at risk Ampulla of Vater cancer 267 CBD cancer Pancreatic cancer
270 289
12 24 Time after surgery (months)
36
0 225
175
126
198 157
137 76
114 42
Overall portal vein (PV) patency rates after pancreatoduodenectomy for periampullary cancer. CBD, common bile duct. P < 0⋅001 (log rank test)
Fig. 3
granulation tissue from early local recurrence, serial CT images were analysed to the end of follow-up to assess changes in soft tissue density around the PV in conjunction with other evidence of tumour recurrence. Among patients with PV stenosis/occlusion, the median time to PV stenosis/occlusion caused by local recurrence, PV thrombosis and granulation tissue was 15⋅1, 16⋅3 and 16⋅2 months respectively (P = 0⋅814). PV stenosis/occlusion was caused by local recurrence more frequently in patients with pancreatic head cancer (65 of 88, 74 per cent) than in those with ampulla of Vater cancer (11 of 25, 44 per cent), whereas postoperative granulation tissue formation caused PV stenosis/occlusion more frequently in patients with ampulla of Vater (6 of 25, 24 per cent) or distal CBD (11 of 49, 22 per cent) cancer than in those with pancreatic head cancer (11 of 88, 13 per cent) (P = 0⋅042). Postoperative complication rates were higher in patients with PV stenosis/occlusion caused by postoperative granulation tissue formation (21 of 28, 75 per cent) than when caused by local recurrence (44 of 108, 40⋅7 per cent) or PV thrombosis (12 of 26, 46 per cent) (P = 0⋅005). In addition, the occurrence of grade B or C pancreatic fistula was more common with granulation tissue formation (8 of 28, 29 per cent) than with local recurrence (10 of 108, 9⋅3 per cent) or PV thrombosis (3 of 26, 12 per cent) (P = 0⋅011).
Portal vein stenosis/occlusion in relation to portal vein resection Of the 55 patients who underwent PV resection, 28 (51 per cent) developed PV stenosis or occlusion. The © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
12
24
36
Time after surgery (months) No. at risk No PV resection PV resection
771 55
557 24
378 10
277 5
Overall portal vein (PV) patency according to PV resection. P < 0⋅001 (log rank test)
Fig. 4
5-year PV patency rate was significantly lower in patients who had PV resection than in those who did not (17 versus 72⋅7 per cent; P < 0⋅001) (Fig. 4). The method of PV reconstruction was not associated with PV patency: 54 per cent (21 of 39) for end-to-end anastomosis versus 40 per cent (6 of 15) for wedge resection versus 0 per cent (0 of 1) for bovine graft interposition (P = 0⋅210). PV patency rates were compared according to tumour location after stage matching. Of patients with stage II disease, the 3-year PV patency rate was significantly lower for those who had PV resection than in patients who did not, both in the group with distal CBD cancer (50 versus 78⋅9 per cent respectively; P = 0⋅032) and in the group with pancreatic head cancer (33 versus 59⋅8 per cent; P < 0⋅001).
Risk factor analysis for portal vein stenosis/occlusion after curative pancreatoduodenectomy Multivariable analysis showed that tumour location (P < 0⋅001), PV resection (P < 0⋅001) and chemoradiotherapy (P = 0⋅044) were independent risk factors for PV stenosis/occlusion after pancreatoduodenectomy with curative intent (Table 2). For pancreatic head cancer, PV resection (OR 4⋅20, 95 per cent c.i. 2⋅01 to 8⋅78; P < 0⋅001) and tumour recurrence (OR 7⋅81, 2⋅85 to 21⋅39; P < 0⋅001) were independent risk factors for PV stenosis/occlusion. www.bjs.co.uk
BJS 2015; 102: 77–84
82
Table 2
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
Risk factors for portal vein stenosis or occlusion Stenosis or occlusion* No (n = 664)
Co-morbidity Yes No Location Ampulla of Vater Distal CBD Pancreas PV resection Yes No Complication Yes No POPF None or grade A Grade B or C Chemoradiotherapy Yes No
Yes (n = 162)
P‡
Odds ratio†
P§
0⋅481 314 (81⋅6) 350 (79⋅4)
71 (18⋅4) 91 (20⋅6)
242 (90⋅6) 221 (81⋅9) 201 (69⋅6)
25 (9⋅4) 49 (18⋅1) 88 (30⋅4)
27 (49) 637 (82⋅6)
28 (51) 134 (17⋅4)
356 (82⋅2) 308 (78⋅4)
77 (17⋅8) 85 (21⋅6)
589 (80⋅6) 75 (79)
142 (19⋅4) 20 (21)
322 (75⋅1) 306 (86⋅2)
107 (24⋅9) 49 (13⋅8)
< 0⋅001
< 0⋅001 1⋅97 (1⋅15, 3⋅37) 2⋅93 (1⋅74, 4⋅93)
0⋅014 < 0⋅001
3⋅28 (1⋅80, 6⋅00)
< 0⋅001
1⋅51 (1⋅01, 2⋅25)
0⋅044
< 0⋅001
0⋅164
0⋅707
< 0⋅001
Values in parentheses are *percentages and †95 per cent c.i. CBD, common bile duct; PV, portal vein; POPF, postoperative pancreatic fistula. ‡χ2 test; §logistic regression.
Portal vein stenosis/occlusion without evidence of disease recurrence Of the 162 patients with PV stenosis/occlusion, 28 (17⋅3 per cent) developed PV stenosis/occlusion without evidence of disease recurrence. Of these patients, six had ampulla of Vater, 11 had distal CBD and 11 had pancreatic head cancer. Causes of PV stenosis/occlusion were postoperative fluid collection, organized haematomas or granulation tissue formation. Median time to PV stenosis/occlusion was 16⋅3 (range 0⋅1–73⋅5) months. Multivariable analysis showed that postoperative pancreatic fistula formation (OR 3⋅18, 95 per cent c.i. 1⋅08 to 9⋅34; P = 0⋅035) was an independent risk factor for PV stenosis/occlusion in patients without evidence of disease recurrence, and PV resection (OR 4⋅49, 0⋅91 to 22⋅13; P = 0⋅065) had marginal significance.
Rare but fatal complications caused by portal vein stenosis/occlusion Twenty-one (13⋅0 per cent) of the 162 patients with PV stenosis/occlusion developed gastric or hepaticojejunostomy varices; 19 had grade D occlusion (100 per cent) and two had grade C stenosis (75–99 per cent). No patient with grade B stenosis developed varices. Five of these 21 patients showed no evidence of disease recurrence; of these, one had undergone PV resection, and two had grade B and three had grade C pancreatic fistula. Among patients with PV stenosis/occlusion, five developed fatal recurrent gastrointestinal bleeding due to gastric © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
or hepaticojejunostomy varices. Gastrointestinal bleeding developed a median of 16⋅7 (range 12⋅2–36⋅5) months after surgery. All five patients underwent PV stent insertion to lower PV pressure. One also had an explorative laparotomy to control the bleeding, which was unsuccessful. Discussion
PV complications after liver transplantation have been well documented because PV stenosis and thrombosis can be potentially devastating and lead to graft failure9 . Less is known, however, about PV complications after pancreatoduodenectomy. PV stenosis can occur during the immediate perioperative period or may manifest many years after surgery. Most patients are asymptomatic, whereas others present with the typical clinical signs of portal hypertension, including gastrointestinal haemorrhage, ascites and splenomegaly10 . Long-term patency of the PV should be examined, because long-term survivors who experience PV stenosis/occlusion may develop PV hypertension. The present study included a large patient cohort who underwent long-term follow-up of the PV after pancreatoduodenectomy with curative intent. The PV patency rate differed significantly according to the site of the primary tumour, being highest in patients with ampullary cancer and lowest in those with pancreatic head cancer. Multivariable analysis also revealed that primary tumour location was an independent risk factor for PV stenosis/occlusion. Tumour recurrence around the PV was the most frequent cause of PV stenosis/occlusion www.bjs.co.uk
BJS 2015; 102: 77–84
Portal vein patency after pancreatoduodenectomy
83
after pancreatoduodenectomy for periampullary cancer. Thus, pancreatic cancer had the highest risk of PV stenosis/occlusion because its recurrence rate was highest. Moreover, most patients with pancreatic cancer developed PV stenosis/occlusion within 6 months after surgery as a result of early recurrence. In contrast, most patients with ampullary or distal CBD cancers who developed PV stenosis/occlusion did so after 12 months, with the PV change in these patients being due to postoperative formation of granulation tissue rather than disease recurrence. Interestingly, the study found that 17⋅3 per cent of patients with PV stenosis/occlusion had no evidence of disease recurrence. After surgery, granulation tissue developed around the PV in these patients, reducing PV diameter. More than 60 per cent of these patients (17 of 28) did not undergo PV resection, and a higher proportion had ampullary or distal CBD cancer. Patients with grade B or C pancreatic fistula tended to develop PV stenosis/occlusion associated with granulation tissue formation. PV resection has been regarded as affecting PV patency. To date, the complication rates reported after pancreatoduodenectomy combined with PV resection have been found to range from 16⋅7 to 54 per cent11 – 20 . However, these morbidity rates included only short-term perioperative complications such as pancreatic fistula, delayed gastric emptying and intra-abdominal abscess formation. Most previous studies have focused on PV thrombosis rates after PV resection. Thrombosis rates immediately and from 6 months to 3 years after PV resection have been reported to range from 0 to 4 per cent15,21 – 25 and from 0 to 40 per cent5,13,26 – 28 respectively. As shown in the present data, the PV thrombosis rate after PV resection was 0 per cent, and all PV thromboses developed in patients who did not undergo PV resection. In addition, types of venous reconstruction were not related to PV patency. In contrast, in the present series, the rate of PV thrombosis as a cause of PV stenosis/occlusion after pancreatoduodenectomy for periampullary cancer was only 16⋅0 per cent. PV patency rates were significantly lower in patients who had PV resection than in those who did not. In addition, 15 (58 per cent) of 26 patients who developed PV stenosis/occlusion within 6 months after surgery had undergone PV resection. Although PV resection did not increase the PV thrombosis rate, PV resection was related to immediate and long-term PV stenosis/occlusion. Therefore, this procedure is not free from morbidity and candidates for PV resection should be selected carefully. Importantly, 13⋅0 per cent of patients with PV stenosis/occlusion developed gastric or hepaticojejunostomy varices, with five (21 per cent) of these 21 patients experiencing fatal recurrent gastrointestinal bleeding. Careful
postoperative surveillance for PV stenosis/occlusion is required, especially in patients with distal CBD or ampulla of Vater cancer because their overall survival is longer and hence they have increased time to develop these serious complications. Moreover, as even patients who did not undergo PV resection or experience disease recurrence developed these fatal complications, the risk of PV stenosis/occlusion and the occurrence of its associated complications should not be overlooked. Because the incidence of complications related to PV stenting is higher than the rate of gastrointestinal bleeding caused by portal hypertension, routine PV stenting is not recommended in patients with asymptomatic PV occlusion. However, an aggressive approach including PV stenting or selective surgical therapy to lower PV hypertension is needed in patients who develop recurrent gastrointestinal bleeding.
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
Acknowledgements
This study was supported by a grant from the National R&D Programme for Cancer Control funded by the Ministry of Health & Welfare, Republic of Korea (no. 1120310) and Seoul National University (no. 30-2013-0100). Disclosure: The authors declare no conflict of interest. References 1 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: 103–108. 2 Ramacciato G, Mercantini P, Petrucciani N, Giaccaglia V, Nigri G, Ravaioli M et al. Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma? Ann Surg Oncol 2009; 16: 817–825. 3 Chua TC, Saxena A. Extended pancreaticoduodenectomy with vascular resection for pancreatic cancer: a systematic review. J Gastrointest Surg 2010; 14: 1442–1452. 4 Han SS, Jang JY, Kim SW, Kim WH, Lee KU, Park YH. Analysis of long-term survivors after surgical resection for pancreatic cancer. Pancreas 2006; 32: 271–275. 5 Kim SM, Min SK, Park D, Min SI, Jang JY, Kim SW et al. Reconstruction of portal vein and superior mesenteric vein after extensive resection for pancreatic cancer. J Korean Surg Soc 2013; 84: 346–352. 6 Kang MJ, Jang JY, Lee SE, Lim CS, Lee KU, Kim SW. Comparison of the long-term outcomes of uncinate process cancer and non-uncinate process pancreas head cancer: poor prognosis accompanied by early locoregional recurrence. Langenbecks Arch Surg 2010; 395: 697–706. 7 Wei BJ, Zhai RY, Wang JF, Dai DK, Yu P. Percutaneous portal venoplasty and stenting for anastomotic stenosis after
BJS 2015; 102: 77–84
84
8
9
10
11
12
13
14
15
16
17
M. J. Kang, J.-Y. Jang, Y. R. Chang, W. Jung and S.-W. Kim
liver transplantation. World J Gastroenterol 2009; 15: 1880–1885. Kim BS, Kim TK, Jung DJ, Kim JH, Bae IY, Sung KB et al. Vascular complications after living related liver transplantation: evaluation with gadolinium-enhanced three-dimensional MR angiography. AJR Am J Roentgenol 2003; 181: 467–474. Woo DH, Laberge JM, Gordon RL, Wilson MW, Kerlan RK Jr. Management of portal venous complications after liver transplantation. Tech Vasc Interv Radiol 2007; 10: 233–239. Settmacher U, Nussler NC, Glanemann M, Haase R, Heise M, Bechstein WO et al. Venous complications after orthotopic liver transplantation. Clin Transplant 2000; 14: 235–241. Howard TJ, Villanustre N, Moore SA, DeWitt J, LeBlanc J, Maglinte D et al. Efficacy of venous reconstruction in patients with adenocarcinoma of the pancreatic head. J Gastrointest Surg 2003; 7: 1089–1095. Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK et al. Pancreaticoduodenectomy with en bloc portal vein resection for pancreatic carcinoma with suspected portal vein involvement. World J Surg 2004; 28: 602–608. Jain S, Sacchi M, Vrachnos P, Lygidakis NJ. Carcinoma of the pancreas with portal vein involvement – our experience with a modified technique of resection. Hepatogastroenterology 2005; 52: 1596–1600. Kurosaki I, Hatakeyama K, Minagawa M, Sato D. Portal vein resection in surgery for cancer of biliary tract and pancreas: special reference to the relationship between the surgical outcome and site of primary tumor. J Gastrointest Surg 2008; 12: 907–918. Capussotti L, Massucco P, Ribero D, Vigano L, Muratore A, Calgaro M. Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes and implications for therapy. Arch Surg 2003; 138: 1316–1322. Riediger H, Makowiec F, Fischer E, Adam U, Hopt UT. Postoperative morbidity and long-term survival after pancreaticoduodenectomy with superior mesentericoportal vein resection. J Gastrointest Surg 2006; 10: 1106–1115. Ouaissi M, Hubert C, Verhelst R, Astarci P, Sempoux C, Jouret-Mourin A et al. Vascular reconstruction during pancreatoduodenectomy for ductal adenocarcinoma of the pancreas improves resectability but does not achieve cure. World J Surg 2010; 34: 2648–2661.
© 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
18 Turrini O, Ewald J, Barbier L, Mokart D, Blache JL, Delpero JR. Should the portal vein be routinely resected during pancreaticoduodenectomy for adenocarcinoma? Ann Surg 2013; 257: 726–730. 19 Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N et al. Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma. J Surg Oncol 2013; 107: 414–421. 20 Kim PT, Wei AC, Atenafu EG, Cavallucci D, Cleary SP, Moulton CA et al. Planned versus unplanned portal vein resections during pancreaticoduodenectomy for adenocarcinoma. Br J Surg 2013; 100: 1349–1356. 21 Bachellier P, Nakano H, Oussoultzoglou PD, Weber JC, Boudjema K, Wolf PD et al. Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile? Am J Surg 2001; 182: 120–129. 22 Carrère N, Sauvanet A, Goere D, Kianmanesh R, Vullierme MP, Couvelard A et al. Pancreaticoduodenectomy with mesentericoportal vein resection for adenocarcinoma of the pancreatic head. World J Surg 2006; 30: 1526–1535. 23 Wang C, Wu H, Xiong J, Zhou F, Tao J, Liu T et al. Pancreaticoduodenectomy with vascular resection for local advanced pancreatic head cancer: a single center retrospective study. J Gastrointest Surg 2008; 12: 2183–2190. 24 Illuminati G, Carboni F, Lorusso R, D’Urso A, Ceccanei G, Papaspyropoulos V et al. Results of a pancreatectomy with a limited venous resection for pancreatic cancer. Surg Today 2008; 38: 517–523. 25 Yekebas EF, Bogoevski D, Cataldegirmen G, Kunze C, Marx A, Vashist YK et al. En bloc vascular resection for locally advanced pancreatic malignancies infiltrating major blood vessels: perioperative outcome and long-term survival in 136 patients. Ann Surg 2008; 247: 300–309. 26 Smoot RL, Christein JD, Farnell MB. Durability of portal venous reconstruction following resection during pancreaticoduodenectomy. J Gastrointest Surg 2006; 10: 1371–1375. 27 Martin RC II, Scoggins CR, Egnatashvili V, Staley CA, McMasters KM, Kooby DA. Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes. Arch Surg 2009; 144: 154–159. 28 Stauffer JA, Dougherty MK, Kim GP, Nguyen JH. Interposition graft with polytetrafluoroethylene for mesenteric and portal vein reconstruction after pancreaticoduodenectomy. Br J Surg 2009; 96: 247–252.
www.bjs.co.uk
BJS 2015; 102: 77–84
