A Multidisciplinary Approach for Abdominal Venous Involvement in Oncologic Resections

A Multidisciplinary Approach for Abdominal Venous Involvement in Oncologic Resections G. Paul Wright,1,2 Jill K. Onesti,1,2 Mathew H. Chung,1,2,3 and M. Ashraf Mansour,1,2,3 Grand Rapids, Michigan

Background: An aggressive surgical approach to locally advanced malignancy is being increasingly used in the absence of distant metastatic disease. This includes resection and reconstruction of major venous structures. We investigated the results of using a multidisciplinary surgical approach in these instances. Methods: The study data were obtained from a university-affiliated hospital from January 1, 2006, to December 31, 2012. All patients who underwent an oncologic resection using a multidisciplinary approach with vascular surgery consultation were included in the analysis. Primary outcomes analyzed included rate of margin positivity, postoperative venous patency, and survival. Secondary outcome measures included operative time, estimated blood loss, and length of hospital stay. Results: A total of 23 patients met criteria for study. Venous involvement included the portal and/or superior mesenteric vein and inferior vena cava in 14 and 9 patients, respectively. Nine patients had clear vascular involvement before surgery and received preoperative consultation. Overall margins were positive in 56.5%, whereas the rate of vascular margin positivity was 30.4%. The postoperative venous patency rate was 65.0%. There were no perioperative mortalities, and median survival was 10 months (range, 4e80). Conclusions: Major venous resections and reconstructions in oncologic surgery are safe but associated with a high rate of positive margins. Future efforts should focus on identifying patients in the preoperative phase to provide opportunity for optimal multidisciplinary planning.

INTRODUCTION Modern imaging modalities, especially computed tomography angiography and magnetic resonance

Presented in part at the American Venous Forum 22nd Annual Meeting, February 13, 2010, Amelia Island, FL. 1 Grand Rapids Medical Education Partners, General Surgery Residency Program, Grand Rapids, MI. 2 Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, MI. 3 Department of Surgical Specialties, Spectrum Health Medical Group, Grand Rapids, MI.

Correspondence to: M. Ashraf Mansour, MD, FACS, 221 Michigan Street, Ste 200A, Grand Rapids, MI 49503, USA; E-mail: ashraf. [email protected] Ann Vasc Surg 2015; 29: 1007–1014 http://dx.doi.org/10.1016/j.avsg.2015.01.012 Ó 2015 Elsevier Inc. All rights reserved. Manuscript received: March 31, 2014; manuscript accepted: January 24, 2015; published online: March 7, 2015.

angiography, have allowed for improved preoperative staging of abdominal malignancies. To achieve maximum benefit and disease free survival, in the absence of distant metastatic disease, an aggressive surgical approach is most often indicated. Dependent on tumor type and location, this may involve the need for resection and reconstruction of major venous structures. Despite advancements in systemic therapy options tailored to individual tumor biology, achieving a negative resection margin remains paramount toward cure.1,2 Common sites of large vein involvement include the portal or superior mesenteric vein (PV/SMV) by tumors of the head of the pancreas or the inferior vena cava (IVC) by renal cell carcinomas or retroperitoneal sarcomas. Data are mixed regarding the efficacy of venous resection among these tumors. A benefit has been identified in renal cell carcinoma with venous extension, with long-term survival observed.3,4 A recent report of portal venous 1007

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resection in pancreatic adenocarcinoma suggests a survival advantage in patients who underwent PV/ SMV resection.5 With these data, the authors even boldly suggested broader applicability of PV/SMV resection on a routine basis in this disease. IVC resection for retroperitoneal sarcoma has also been performed with success.6 Our institution has used a multidisciplinary surgical approach to large vein involvement that includes vascular surgery consultation for resection and reconstruction of these vital structures. We sought to investigate these challenging cases to assess the adequacy of resection, postoperative patency, and survival in this population.

MATERIALS AND METHODS The study was designed as a retrospective review. The study protocol was approved by the institutional review board, and a waiver of informed consent was obtained. All major venous resections and reconstructions were included from January 1, 2006, to December 31, 2012. The primary teams included surgical oncology and urologic surgery, whereas consultations were performed by vascular surgery in all cases and cardiothoracic surgery in select cases. All patients had preoperative computed tomography for staging. Positron emission tomography was not used routinely and in the cases where it was used, it did not effect treatment planning. Venous resections and reconstructions were performed by the vascular surgery team in each case. Type of reconstruction was chosen at the discretion of the vascular surgeon based largely on the extent of involvement. Intravenous heparin was used routinely once proximal and distal control of the venous structure was obtained. In one case, cardiothoracic surgery consultation was obtained to place the patient on cardiopulmonary bypass and full hypothermic circulatory arrest, whereas off-pump venovenous bypass was used in a second case. Standardized vascular margin assessment was performed in each case. Data collected included demographics, surgical details, postoperative venous patency, use of anticoagulation or antiplatelet therapy, margin status, hospital stay, and survival. Venous patency was determined based on computed tomography throughout the follow-up period. A KaplaneMeier curve was constructed to describe survival patterns based on the pathologic diagnosis. Comparisons were made between groups based on the involved vein, margin status, and whether the procedure was planned. Subgroup analysis of pancreatic

Annals of Vascular Surgery

tumors was performed as this encompassed the largest group of pathologic diagnosis. Differences between groups were analyzed by 2-tailed Fisher exact test for categorical variables and the t test for parametric continuous variables. The ManneWhitney test was used for continuous and ordinal variables if the results were nonparametric. A P value < 0.05 was considered significant. Multivariate analysis was not able to be performed because of the small sample size. Statistical analysis was performed using IBM SPSS Statistics v. 20.0 (Armonk, NY).

RESULTS A total of 23 patients underwent major venous resection and reconstruction during the study period. Procedures were performed by 7 primary surgeons and 6 vascular surgeons. One vascular surgeon (M.A.M.) saw 7 of 9 planned consultations, whereas the other 16 cases were distributed equally among the other surgeons. A complete case listing is provided in Table I. The median age of the cohort was 67 years (range, 38e82), and 7 patients were women. The most common primary tumor sites were the head of the pancreas (n ¼ 11, 47.8%), retroperitoneum (n ¼ 4, 17.4%), and kidney (n ¼ 3, 13.0%). Venous involvement included the PV/SMV (n ¼ 14, 60.9%) and IVC (n ¼ 9, 39.1%). PV/SMV Resections Diagnoses associated with PV/SMV resection were pancreatic adenocarcinoma (n ¼ 11, 78.6%), periampullary adenocarcinoma (n ¼ 1, 7.1%), pancreatic neuroendocrine tumor (n ¼ 1, 7.1%), and gallbladder adenocarcinoma (n ¼ 1, 7.1%). The most common type of resection and reconstruction of the PV/SMV was primary repair (n ¼ 10, 71.4%). Other techniques included saphenous vein patch venoplasty (n ¼ 2, 14.3%), polytetrafluorethylene (PTFE) graft (n ¼ 1, 7.1%), and lumbar vein transposition (n ¼ 1, 7.1%). Postoperative thromboprophylaxis included aspirin in all patients, clopidogrel in 1 patient, and warfarin therapy with bridging heparin in 1 patient in this group following near-immediate postoperative thrombosis. Follow-up imaging was available in 12 of 14 patients. The overall patency rate was 41.7% with a median follow-up of 7 months (range, 2e24). Positive margins were found in 9 of 14 cases (64.3%) overall with positive vascular margins in 4 of 14 cases (28.6%). The median hospital length of stay was 21 days (range, 8e28). Major complications among this

Patient

Diagnosis

Primary procedure

Vascular procedure

Reconstruction

Planned vascular surgery consult

1 2 3

Metastatic sarcoma Renal cell carcinoma Pancreatic adenocarcinoma Retroperitoneal germ cell tumor Pancreatic adenocarcinoma Renal cell carcinoma Leiomyoma Leiomyosarcoma

Right adrenalectomy Right radical nephrectomy Pancreaticoduodenectomy

IVC tumor resection IVC tumor resection Portal vein resection

Primary repair Primary repair Primary repair

Yes Yes Yes

276 163 468

1,500 Yes 4,000 Yes 1,350 N/A

Neg Pos Pos

5 23 8

Retroperitoneal tumor resection Pancreaticoduodenectomy

IVC resection

PTFE graft

Yes

414

800 Yes

Neg

24

Portal vein resection

Primary repair

Yes

380

800 Yes

Pos

24

IVC tumor resection IVC tumor resection IVC tumor resection

Yes Yes Yes

237 337 211

300 Yes db Yes 400 d

Pos Neg Neg

80a 72a 65a

IVC/common iliac vein resection

Primary repair Primary repair Saphenous vein venoplasty Saphenous vein graft

No

567

1,000 Yes

Neg

51

4 5 6 7 8

Colonic adenocarcinoma

10

Pancreatic adenocarcinoma

11

Pancreatic adenocarcinoma Pancreatic adenocarcinoma Pancreatic adenocarcinoma Pancreatic neuroendocrine tumor

12 13 14

Renal cell carcinoma Liposarcoma

17

Pancreatic adenocarcinoma Pancreatic adenocarcinoma

18

Patency

Margin status

Overall survival (months)

Right radical nephrectomy IVC tumor resection Retroperitoneal tumor resection Right radical nephrectomy, retroperitoneal tumor resection Distal pancreatectomy, splenectomy, colectomy, partial gastrectomy Pancreaticoduodenectomy

Left renal vein/ IVC resection

Lumbar vein transposition

No

346

700 Yes

Pos

9

SMV resection

Primary repair

No

304

400 No

Neg

9

Pancreaticoduodenectomy

Portal vein resection

No

330

700 d

Pos

4

Total pancreatectomy, splenectomy Distal pancreatectomy, splenectomy, cholecystectomy, hepatic ablation Left radical nephrectomy Right radical nephrectomy, adrenalectomy

Portal vein resection

Saphenous vein venoplasty Primary repair

No

342

1,500 No

Pos

9

Portal vein resection

Primary repair

No

304

750 No

Neg

27

IVC tumor resection IVC resection

No Yes

314 330

1,400 Yes 3,500 Yes

Pos Neg

10 8

No

291

500 No

Pos

9

No

451

2,200 No

Neg

16

Pancreaticoduodenectomy

Portal vein resection

Primary repair PTFE graft, reimplant of left renal vein Primary repair

Pancreaticoduodenectomy

Portal vein resection

PTFE graft

(Continued)

1009

15 16

EBL (mL)

Multidisciplinary approach for abdominal venous involvement

9

Operative time (min)

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Table I. Case listing

group included a myocardial infarction in 1 patient and reoperation in 2 patients. The first reoperative patient had persistent hemodynamic instability and underwent reexploration with right hepatic lobectomy due to hepatic ischemia thought to be due to occlusion of right hepatic artery. The second patient had a second-look laparotomy due to concern for intestinal ischemia but did not need further intervention. The other patients with PV thrombosis had elevated liver function tests prompting reimaging and did not experience significant clinical sequelae after initiation of therapeutic anticoagulation.

Neg

Pos

3,000 No

700 No

6

Pos 400 Yes

27a

Pos 800 Yes

4

Pos

15

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850 Yes

10

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313 No 23

Neg, negative; Pos, positive; EBL, estimated blood loss; N/A, not available. a Patient alive at latest follow-up. b Re-infused from cell saver.

SMV resection Pancreaticoduodenectomy

Primary repair

339 No

Periampullary adenocarcinoma Pancreatic adenocarcinoma 22

Portal vein resection

Portal vein resection, hepatic artery repair Gallbladder adenocarcinoma

20

21

Pancreaticoduodenectomy, right colectomy, right hepatectomy Pancreaticoduodenectomy

Primary repair

316

No Saphenous vein venoplasty, reimplant jejunal branch Primary repair No Portal vein resection Pancreaticoduodenectomy

352

439 Portal vein resection

Pancreatic adenocarcinoma Pancreatic adenocarcinoma 19

Pancreaticoduodenectomy

Primary repair

No

IVC Resections Patients undergoing IVC resection had a wider variety of diagnoses including soft tissue sarcoma (n ¼ 3, 33.3%), renal cell carcinoma (n ¼ 3, 33.3%), retroperitoneal germ cell tumor (n ¼ 1, 11.1%), metastatic colonic adenocarcinoma (n ¼ 1, 11.1%), and leiomyoma (n ¼ 1, 11.1%). Reconstruction was performed most commonly using primary repair (n ¼ 5, 55.5%), and also included saphenous vein patch venoplasty (n ¼ 2, 22.2%) and PTFE graft (n ¼ 2, 22.2%). Two cases required venovenous bypass for 37 and 112 min, respectively. All patients were treated with aspirin postoperatively, and 2 patients were additionally placed on bridging heparin with warfarin for anticoagulation. This was based on surgeon preference as no clear indication was elicited from the medical record. For the 8 patients with follow-up imaging, patency of the IVC was 100% at a median follow-up of 15 months (range, 1e50 months). Positive margins were identified in 3 of 9 (33.3%) specimens, all involving the vascular margin. The median hospital length of stay was 6 days (range, 4e10). Only one major complication occurred in this group. A small duodenal leak adjacent to an implanted PTFE graft resulted in a graft infection. The graft remained patent, but the patient underwent reexploration and explantation to control the infection. Patients with IVC involvement were younger and more likely to have undergone planned consultation, compared with those who had PM/SMV involvement (Table II). They also experienced longer hospital stays, decreased patency, and worsened median survival time compared with those who had IVC involvement. Surgical Planning Planned preoperative consultations were obtained in 9 of 23 (39.1%) cases. In the remainder, intraoperative consultation was obtained because of unforeseen extent of venous involvement. These

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Table II. Vein involvement

a

Age, years Gender (male) Reconstruction Primary repair Patch venoplasty Graft OR time (min)a EBL (mL)a Margins positive Planned consultation Length of stay (days)a Patency Survival (months)a

PV/SMV (n ¼ 14)

IVC (n ¼ 9)

P value

67.5 (51e82) 9/14

55 (38e78) 7/9

0.01 0.66

11/14 2/14 1/14 340.5 (291e468) 775 (400e3,000) 9/14 2/14 21.5 (8e28) 5/12 9 (4e27)

5/9 1/9 3/9 314 (163e567) 1,000 (300e4,000) 3/9 7/9 6 (4e10) 8/8 24 (5e80)

0.36

0.16 0.52 0.21 0.007 <0.001 0.01 <0.001

Planned (n ¼ 9)

Unplanned (n ¼ 14)

P value

55 (38e79) 7/9

67.5 (51e82) 9/14

2/9 7/9

11/14 2/14

6/9 1/9 2/9 330 (163e468) 800 (300e4,000) 4/9 8 (4e27) 7/7 24 (5e72)

10/14 2/14 2/14 334.5 (291e567) 775 (400e3,000) 8/14 20 (6e28) 6/13 9 (4e51)

EBL, estimated blood loss; OR, operating room. a Data expressed as the median (range).

Table III. Planned versus unplanned cases

a

Age, years Gender (male) Vein involved PV/SMV IVC Reconstruction Primary repair Patch venoplasty Graft OR time (min)a EBL (mL)a Margins positive Length of stay, daysa Patency Survival, monthsa

0.04 0.66 .01

>0.99

0.37 0.69 0.68 0.01 0.04 <0.001

EBL, estimated blood loss; OR, operating room. a Data expressed as the median (range).

instances were predominant in patients with pancreatic adenocarcinoma. Subgroup analysis revealed patients who underwent planned procedures were younger and more likely to have IVC involvement, shorter length of stay, higher patency rates, and longer survival compared with those who underwent unplanned procedures (Table III). Survival Median survival for the entire cohort was 10 months (range, 4e72). There were 4 patients alive at the time of data collection with follow-up of 27, 65, 72, and 80 months. There were 11 patients with pancreatic adenocarcinoma who were all deceased at follow-up (median survival, 9 months; range,

4e24; Fig. 1). When selecting for patients with diagnoses other than pancreatic adenocarcinoma, median survival improved to 24 months (range, 4e 80). Survival for patients with IVC resections was equivalent by margin status (37.7 ± 37.2 months for positive margins versus 37.5 ± 29.1 months for negative marginseP ¼ 0.99, mean ± standard deviation). Conversely, for PV/SMV resections survival with positive margins was 10.2 ± 6.1 months versus 17.0 ± 9.8 months with negative margins (P ¼ 0.13).

DISCUSSION Improvements in the resolution of multidetector computed tomography and magnetic resonance

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Fig. 1. Survival based on pathologic diagnosis.

imaging have helped in preoperative staging and planning for possible curative resection of abdominal malignancies. The goal remains complete extirpation of tumor with clear margins. These resections often involve major venous structures including the PV/SMV and the IVC and are best handled by a multidisciplinary team approach. Recent studies have shown vascular resection for pancreatic cancer to have similar morbidity as a standard procedure while improving survival compared with palliative therapy alone.5,7 In contrast, other studies have shown slightly higher perioperative mortality rates but similar survival rates.8,9 The key for long-term survival in this disease remains the ability to achieve an R0 resection. In renal cell carcinoma, tumor extension and invasion into the IVC complicate the resection. There have been many reports of successful resection of renal cell tumors extending up into the right atrium with good outcomes.3,4 Resection of retroperitoneal sarcomas involving the IVC have been accomplished with satisfactory results.6 This report details the technique and outcomes of major venous resection and reconstruction for malignancy using a multidisciplinary surgical team that included performance of venous resection by vascular surgeons in all cases. Twenty-three patients were treated with this approach with R0 resection rates of 35.7% and 66.6% for the PV/SMV and IVC, respectively. When only looking at the vascular margin, however, the rates of positivity were comparable at 28.6% and 33.3% for the PV/SMV and IVC, respectively. There were no perioperative mortalities. Two significant procedure-related morbidities occurred in this cohort. The first resulted from

Annals of Vascular Surgery

a duodenal leak after resection of a retroperitoneal sarcoma, which required reexploration and explantation of the PTFE graft used to reconstruct the IVC. The second resulted from hepatic ischemia after an extended pancreaticoduodenectomy for which a portion of the PV was resected and repaired primarily. The patient required emergent reexploration within the first 48 hours and underwent a right hepatic lobectomy. Aside from these 2 adverse events, the performance of large vein resection and reconstruction in oncologic procedures appears to be relatively safe. The most common type of reconstruction used in our series was primary repair of the involved vein (65.2%). From a technical perspective, this is the most simple and rapid technique for reconstruction. In our series, however, this technique was associated with a higher rate of positive margins and a 38% rate of venous thrombosis in the immediate postoperative period. This was despite a similar distribution of technique based on the vein involved. A recent report investigated vascular outcomes based on the type of conduit used, however, the currently available data are limited.10 The pros and cons of all available options are important to consider in deciding the most appropriate reconstructive option. The site of venous involvement is an important factor in oncologic resections. Involvement of the PV/SMV is most commonly seen in adenocarcinoma of the pancreatic head. Our data demonstrate higher margin positivity, decreased patency, and lower rate of preoperatively planned vascular consultation for PV/SMV compared with IVC resection and reconstruction. Interestingly, the rate of vascular margin positivity was equivalent between groups likely because of the other positive margins identified in patients with pancreatic adenocarcinoma. Pancreatic adenocarcinoma represents one of the most aggressive malignancies, and preoperative imaging does not always demonstrate the true extent of venous or soft tissue involvement. Furthermore, the rate of margin positivity for pancreatic adenocarcinoma in contemporary studies using a rigorous, standardized pathologic approach is >75%.2 This is reflected in our high positive margin rate in this group. For comparison, our institution has previously reported positive margin rate of 38% after pancreaticoduodenectomy for all malignancies which is comparable to the results found in this cohort.11 Patency data for PV/SMV and IVC reconstruction are limited. In our study, the PV/SMV patency rate was 41.7% compared with 100% for the IVC. As stated earlier, this may have been related to a higher

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incidence of primary repair in the PV/SMV group. The standard postoperative medication regimen consisted only of aspirin therapy, with deviations from this in 4 patients. One patient was continued on clopidogrel, whereas 3 were treated with intravenous heparin followed by warfarin. In 1 patient, intravenous heparin was initiated after PV thrombosis was identified in the immediate postoperative period before the initiation of aspirin therapy. The other 2 cases were in IVC resections and based on surgeon preference. No clear indication was identified as these patients did not experience thrombotic complications. Further study on the factors impacting long-term patency is warranted. Survival for locally advanced malignancies such as those associated with venous involvement is typically poor. The median survival for the cohort was 10 months, influenced greatly by the high proportion of cases of pancreatic adenocarcinoma whose median survival was 9 months. Nonoperative management of advanced pancreatic adenocarcinoma is rarely associated with survival beyond a few months. Our data do not demonstrate as drastic an improvement in survival as previous reports; however, survival was demonstrated out to 24 months which would not be otherwise possible with nonoperative management. There were 4 patients in the study with a survival of greater than 4 years, 3 of whom remained alive at the time of data collection. These all involved the IVC, indicating that resection of this vein can offer long-term survival. Our study did not include any patients who underwent neoadjuvant therapy, which may be a tool to more rigorously select patients who will receive the most benefit from en bloc venous resection and reconstruction. The main limitations of our study are the small sample size and differing tumor biology. As many of these patients were referred from a far distance away, they often received their adjuvant therapy closer to home. The records of adjuvant therapy in the data set are incomplete, and the effect of this on survival is unknown. Despite the multidisciplinary approach, there was no standardization in terms of reconstructive choice, which was left to the individual vascular surgeon, introducing potential selection bias. These data add to the growing body of evidence in the literature suggesting a benefit of venous resection for oncologic purposes in select patients. In addition, a multidisciplinary approach with preprocedure planning appears to result in improved outcomes. Patients with planned resections, as noted by preoperative rather than intraoperative vascular surgery consultation, had higher patency rates and

improved survival. They also had a nonstatistically significant reduction in operative time. Although if the cohort were larger, we suspect this trend would continue. When the secondary team is prepared for the case, the transition is accomplished with much greater efficiency, leading to less time under general anesthesia for the patient. Although the results are confounded by the increase in the number of PV/ SMV resections and hence pancreatic adenocarcinomas in the unplanned group, these results reinforce the benefit of complete preoperative multidisciplinary involvement including vascular surgery consultation when venous resection may be required. Finally, the implications from these data are that widely aggressive resections to achieve negative margins combined with graft reconstruction may offer the most benefit to this population due to the high rate of margin positivity and the decreased patency rates observed with primary repair. Based on the patency and margin data demonstrated here, this has become a focus for improvement at our institution and will be the subject of further study. In conclusion, major venous involvement by malignant neoplasms can be successfully treated by resection and reconstruction using a multidisciplinary team approach. Improved outcomes were noted in patients who were evaluated by vascular surgeons preoperatively rather than those performing intraoperative consultation. Careful preoperative planning and identification of patients who may require major venous resection is crucial toward achieving good outcomes.

REFERENCES 1. Toomey P, Hernandez J, Morton C, et al. Resection of portovenous structures to obtain microscopically negative margins during pancreaticoduodenectomy for pancreatic adenocarcinoma is worthwhile. Am Surg 2009;75:804e9. 2. Verbeke CS, Menon KV. Redefining resection margin status in pancreatic cancer. HPB (Oxford) 2009;11:282e9. 3. Parra J, Drouin SJ, Hupertan V, et al. Oncological outcomes in patients undergoing radical nephrectomy and vena cava thrombectomy for renal cell carcinoma with venous extension: a single-centre experience. Eur J Surg Oncol 2011;37:422e8. 4. Helfand BT, Smith ND, Kozlowski JM, et al. Vena cava thrombectomy and primary repair after radical nephrectomy for renal cell carcinoma: single-center experience. Ann Vasc Surg 2011;25:39e43. 5. Turrini O, Ewald J, Barbier L, et al. Should the portal vein be routinely resected during pancreaticoduodenectomy for adenocarcinoma? Ann Surg 2013;257:726e30. 6. Fiore M, Colombo C, Locati P, et al. Surgical technique, morbidity, and outcome of primary retroperitoneal sarcoma involving inferior vena cava. Ann Surg Oncol 2012;19: 511e8.

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7. Yekebas EF, Bogoevski D, Cataldegirmen G, 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;247:300e9. 8. Gong Y, Zhang L, He T, et al. Pancreaticoduodenectomy combined with vascular resection and reconstruction for patients with locally advanced pancreatic cancer: a multicenter, retrospective analysis. PLoS One 2013;8:e70340.

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9. Chakravarty KD, Hsu JT, Liu KH, et al. Prognosis and feasibility of en-bloc vascular resection in stage II pancreatic adenocarcinoma. World J Gastroenterol 2010;16:997e1002. 10. Kim SM, Min SK, Park D, et al. Reconstruction of portal vein and superior mesenteric vein after extensive resection for pancreatic cancer. J Korean Surg Soc 2013;84:346e52. 11. Wright GP, Koehler TJ, Davis AT, et al. The drowning whipple: perioperative fluid balance and outcomes following pancreaticoduodenectomy. J Surg Oncol 2014;110:407e11.