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Distal Pancreatectomy for Body-Tail Pancreatic Cancer: Is There a Role for Celiac Axis Resection?
Original Paper Pancreatology 2010;10:491–498 DOI: 10.1159/000276984
Received: July 20, 2009 Accepted after revision: January 6, 2010 Published online: August 19, 2010
Distal Pancreatectomy for Body-Tail Pancreatic Cancer: Is There a Role for Celiac Axis Resection? Cosimo Sperti Mattia Berselli Sergio Pedrazzoli IV Surgical Clinic, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
Key Words Advanced pancreatic cancer ⴢ Distal pancreatectomy ⴢ Celiac axis resection ⴢ Common hepatic artery ⴢ Extended resection ⴢ Modified Appleby operation
Abstract Background/Aims: Body-tail pancreatic cancer is an aggressive disease with a low resectability rate and a poor prognosis. Celiac axis invasion usually contraindicates resection. The aim of this study was to analyze the feasibility of distal pancreatectomy (DP) with celiac axis resection (DP-CAR) for locally advanced body-tail pancreatic cancer. Methods: All DPs performed between January 1989 and December 2007 were considered. DP and DP-CAR were reviewed for pre-, intra- and postoperative data. An extensive, detailed literature review on DP and DP-CAR was also performed. Results: DP was performed in 49 of our patients, and 745 cases were retrieved from the literature. The overall morbidity and mortality rates were 32.0 and 3.0%, respectively. We performed DPCAR in 5 patients with no mortality but 80% morbidity. A further 90 patients were retrieved from the literature. Arterial reconstruction was needed in 1/5 of our patients and in 13/90 of patients in the literature. Collaterals from superior mesenteric artery maintained adequate hepatic artery blood flow in the remaining 81 patients. The overall morbidity and mortality rates were 40.6 and 2.1%, respectively. The
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median survival ranged between 4.5 and 25 months after DP and was 13 months after DP-CAR. Conclusions: DP-CAR improves resectability without increasing the mortality rate. The complication rate after DP-CAR was higher than after DP, but still within the range of extended DP. DP-CAR should be considered for the inclusion among the ‘extended’ procedures for the treatment of body-tail pancreatic cancers invading the celiac axis. Copyright © 2010 S. Karger AG, Basel and IAP
Introduction
Patients with resectable pancreatic cancer account for only 15–20% of all adenocarcinomas of the pancreas [1, 2]. Unresectability is usually due to encasement of the celiac axis (CA), or superior mesenteric artery or distant metastases, identified either by high-quality computed tomography (CT) [3] or intraoperatively [4]. This is often the case in body-tail pancreatic cancer, which tends to be found in a more advanced stage, when the tumor’s extension frequently makes its resection impossible or pointless [2]. One of the reasons why body-tail pancreatic cancer may be unresectable is due to the encasement of the CA and of the origin of the common hepatic artery (CHA), usually associated with severe pain. Cancer invading the CA is considered a locally advanced, unresectProf. Sergio Pedrazzoli, MD, FACS Department of Medical and Surgical Sciences Clinica Chirurgica IV, Via Giustiniani 2 IT–35128 Padova (Italy) Tel. +39 049 821 8827, Fax +39 049 821 8829, E-Mail sergio.pedrazzoli @ unipd.it
able, primary tumor [3, 5]. En bloc resection of the CA and CHA can theoretically improve the resectability of body-tail pancreatic cancer, however. Appleby, a Canadian surgeon, was the first to describe a distal pancreatectomy (DP) with CA resection (DP-CAR) and en bloc resection of the stomach, spleen, left pancreas, and CHA in a patient with gastric cancer in 1953 [6]. Nimura et al. [7] performed the first DPCAR in a patient with body-tail pancreatic cancer in 1976. To date, DP-CAR for the surgical treatment of body-tail pancreatic cancer has been reported in a limited number of patients, mainly by Far Eastern authors [7–22], while experience with this operation in Western countries is limited and more recent [23–28]. The indication for DP-CAR was recently extended to patients without any direct invasion of the CA to increase the radical resection (R0) rate for advanced body-tail pancreatic cancer [18]. The inclusion of DP-CAR in the surgical armamentarium is still widely debated because its efficacy in terms of postoperative complications and mortality and survival rates has yet to be clearly elucidated. This paper reports our experience with DP and DPCAR, for body-tail pancreatic cancer, analyzing postoperative outcome, pain control, and overall and diseasefree survival. An extensive, detailed review was also conducted on cases of DP and DP-CAR for pancreatic cancer reported in the English literature.
Lymphadenectomy includes nodes of the CA, splenic artery, hilum of the spleen, inferior border of the body-tail and anteriorsuperior region of the CHA [30]. Distal Pancreatectomy with Celiac Axis Resection After performing a wide upper midline incision and confirming that disease is localized, the CHA, the gastroduodenal artery and the mesenteric-portal confluent are exposed to verify the feasibility of the procedure. A DP-CAR is contraindicated when any invasion of the CHA near to the origin of the gastroduodenal artery, of the CA at its origin from the aorta, and of para-aortic region is found. The superior mesenteric artery is skeletonized on its anterior and left side from the inferior pancreaticoduodenal artery to its origin from the aorta, carefully preserving the pancreaticoduodenal arterial arcade to maintain adequate hepatic artery blood flow. The CA is exposed at its origin from the aorta on its right side, eventually transecting the left gastric artery, and occluded with a Cooley clamp. CHA is also occluded distal to the tumor, but proximal to the gastroduodenal artery, and the pulses in the right and left hepatic arteries are verified. If inadequate pulses are found, the procedure implies the need of revascularization of the CHA. The CA and the CHA are then transected, and the pancreas is divided along the right side of the portal vein. The right gastroepiploic and right gastric artery are preserved, together with the whole stomach. The spleen and the pancreatic bodytail are then removed along with the left adrenal gland if necessary. Resection of the mesenteric-portal confluent and/or of other organs involved is performed if necessary. Literature Review A focused literature review was conducted on the surgical treatment of body-tail pancreatic cancer, using the Medline database for studies published up until June 2009, and comparing clinical data and outcomes following DP and DP-CAR. The latest search was conducted in June 2009. References mentioned in articles were also checked offline.
Materials and Methods Personal Experience All patients undergoing DP for pancreatic cancer between January 1989 and December 2007 were reviewed and classified as DP or DP-CAR. Details were retrospectively collected on patients’ age, sex and preoperative clinical data, tumor imaging findings, the characteristics of the surgical specimen and histological findings, postoperative morbidity and mortality rates, postoperative outcome, pain control, follow-up and survival. Tumors were staged according to the pTNM (UICC) classification [5]. Pancreatic fistula was defined according to the criteria of Yeo et al. [29]. Follow-up included physical examination, routine laboratory tests, determining tumor markers (CEA and CA 19–9), and abdominal ultrasound and/or CT every 3 months. FDG-PET or PET/CT was performed where clinically indicated. Distal Pancreatectomy The pancreas is transected along the right border of the mesenteric-portal confluence; the splenic artery is transected at its origin from the CA. Resection of the mesenteric-portal confluent, and/or other organs involved is performed whenever necessary.
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Results
Between January 1989 and December 2007, 168 patients were referred to our department for body-tail pancreatic cancer. Fifty-four underwent surgical treatment: 49 had a DP and 5 had a DP-CAR. Among the 49 who underwent DP, there were 23 males and 26 females with a median age of 63.8 years (range 41–87). Severe pain was reported before surgery by 38 patients (77.6%). The median operating time was 231 min (range 180–325) and the mean and median hospital stay was 16.7 and 14 days, respectively (range 6–45). Thirteen patients (26%) had postoperative complications, including 6 pancreatic fistulas (12.2%). One patient (2%) died of myocardial infarction. R0 was achieved in 32 patients (65%), R1 in 13, and R2 in 4 patients. The mean and median survival times were 36.6 and 12.0 months (range 0–96), with a 12.2% 5-year survival rate. Sperti/Berselli/Pedrazzoli
Table 1. Patients’ characteristics
Patient Age/ No. sex
Symptoms
Preoperative tumor staging
Size mm
Resected structures
Morbidity
Treatment of complications
R
AGR, TC, LN and LA
colonic fistula
reoperation (83rd R0 postoperative day)
no
no
R1
postoperative bleeding
reoperation
R2
1
41/M back pain
vascular (CA, splenic vein), 60 gastric and renal encasement
2
70/M abdominal pain
vascular encasement (CA, splenic vein)
25
3
58/M abdominal and back vascular encasement pain/weight loss/diabetes (CA, splenic vein)
30
4
72/F
abdominal and back pain/weight loss
vascular encasement (CA, splenic artery)
40
pancreatic fistula radiological drain
R0
5
73/F
abdominal and back pain vascular encasement (CA, splenic artery)
40
pancreatic fistula radiological drain
R0
MPVR
AGR = Atypical gastric resection; TC = transverse colon resection; LN = left nephrectomy; LA = left adrenalectomy; MPVR = mesenteric-portal vein resection.
Details of the 5 patients who underwent DP-CAR are reported in table 1. All 5 patients had poorly-controlled severe pain before the operation. CT had detected CA invasion in all 5 patients and retroperitoneal invasion in 4. The origin and at least 1 cm of the CA appeared to be unaffected by tumor invasion in all patients. After excluding any distant metastases, patients underwent surgical exploration without neoadjuvant chemotherapy or radiotherapy. Three patients (table 1, No. 2, 4 and 5) underwent DP-CAR alone, while a partial gastric and colonic resection, together with left adrenalectomy, nephrectomy, and reconstruction of the CHA, was also performed in one (table 1, No. 1); the 5th patient (table 1, No. 3) had DP-CAR plus tangential resection of the mesenteric portal confluent. The median operating time was 233 min (range 190–285) and the median hospital stay was 33.6 days (range 14–92). There were no postoperative deaths, while postoperative complications occurred in 80% of patients (table 1). One developed a colonic fistula due to colectomy and was reoperated 83 days after the DP-CAR. One (table 1, No. 3) required emergency reoperation within 24 h of the DP-CAR for intraperitoneal bleeding. Two patients developed a lowoutput pancreatic fistula that closed spontaneously without prolonging their hospital stay. At discharge, none of the patients needed analgesics or complained of severe diarrhea. An R0 resection was achieved in 3 patients, an R1 in one, and an R2 in one (table 1). Four patients had a G2 (moderately differentiated) and one (No.
3) had a G3 (poorly differentiated) pancreatic cancer. Lymph node metastases were found in all but one (No. 1) of the patients. Median disease-free survival was 8 months (range 4–13), and median overall survival was 10 months (range 8–27). Two patients (No. 1 and 3) developed peritoneal metastases and died 14 and 10 months after DP-CAR, respectively. Liver metastases developed in one patient (No. 2) and lung metastases in another (No. 4): they died 10 and 8 months after DP-CAR, respectively. One patient (No. 5) underwent excision of a tumor relapse at the wound site of laparotomy 13 months after DP-CAR. Two months later, FDG-PET/CT revealed tumor recurrence in the pancreatic bed. The patient was given chemotherapy and stereotactic radiotherapy, and died of disseminated disease 27 months after primary resection. No pain or severe diarrhea relapsed in our patients until their tumor recurred. Adjuvant treatment was given to 3/5 patients after DPCAR and to 33/48 survivors (68.8%) after DP. The outcome of the literature review on DP-CAR is shown in table 2. The overall mortality and morbidity rates were 2.1 and 40.6%, respectively. The R0 resection rate was 71.2%, pain control was achieved in 97% of 32 patients (13 further patients were pain free preoperatively), postoperative diarrhea was registered in 41.9% of 43 patients and the mean and median survival times were 18.5 and 13 months (range 2–156), respectively, with a 3.9% 5-year survival (3/77 patients). Patients whose data
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Table 2. Literature review of DP-CAR for pancreatic cancer
First author
Year
PaDeaths Mortients bidity
R0
dead
Nimura [7] Imaizumia Fujitaa Yamamoria Ozaki [8] Mayumi [9] Kimura [10] Konishi [11] Miyakawa [12]
1976 1979 1987 1996 1996 1997 1997 2000 2002
1 1 4 1 1 6 1 4 8
0 0 2 0 0 0 0 0 0
NR NR NR NR NR 2 0 1 3
NR NR NR NR NR NR 1 1 NR
Sasson [23] Yamaguchi [13] Liu [14] Hirai [15] Lin [16] Makary [24] Gagandeep [25] Shimada [17] Hirano [18]c
2002 2003 2003 2005 2005 2005 2006 2006 2007
4 2 1 1 1 1 3 12 23
0 0 0 0 0 0 0 0 0
NR 1 0 NR 0 0 1 NR 11
NR 0 NR 0 NR 1 3 NR 21
Hishinuma [19]
2007
7
0
2
4
Wu [20] Chen [21] Stitzenberg [26] Bonnet [27] Machado [28] Mizutani [22] Present series
2007 2008 2008 2009 2009 2009
1e 1 2 1 1 2 5
0 0 0 NR 0 0 0
1 0 2 NR 0 0 4
NR 1 0 NR NR 2 3
95
2/94 28/69 (2.1%) (40.6%) NR: 26
Total
Survival, months
37/52 (71.2%) NR: 43
alive
NR 3 4, 7
4, 6, 9, 10, 31 5, 10, 14, 18 7, 7, 7, 9, 11, 20, 21, 43 10, 13 8, 14 8 NR 30 NR
11 156 59 18
22, 27
14, 14, 34 median: 17b 4, 5, 6, 10, 11, 14, 16, 18, 21 4, 13, 17, 19, 21, 42, 78 2 11 17, 17 NR 13 6g 8, 10, 10, 14, 27 mean: 18.3 median: 13
1, 2, 4, 5, 5, 11, 18, 18, 22, 27, 32, 35, 40, 62
NRf 8
Pain control
Diarrhea
NR NR NR NR NR NR 1/1 NR NR
NR NR NR NR 1/1 NR 0/1 3/4 NR
NR 2/2 1/1 NR NR NR 3/3 NR 10/10d
NR NR 0/1 NR NR NR NR NR 8/23
6/7
5/7
NR 1/1 NR 1/1 1/1 NR 5/5
NR NR NR NR 0/1 NR 1/5
31/32 (97%) NR: 50d
18/43 (41.9%) NR: 52
NR = Not reported. a Reported by Kimura et al. [10]. b Zero survivors at 2 years. c Survival of each of the 23 patients kindly communicated by the author. d Thirteen patients pain free preoperatively. e Sarcomatoid carcinoma. f Seven Appleby’s procedures, but only one for pancreatic cancer; one of seven still alive. g Not related to pancreatic cancer.
for morbidity (26/95), R0 resection (43/95), pain control (50/95) and diarrhea (52/95) were not reported are also shown in table 2. The outcome of the literature review on DP [17, 31–50] is shown in table 3. The overall mortality and morbidity rates were 3.0% (range 0–21%) and 32% (range 15–54%), respectively. The R0 resection rate was 69.7%, and the 494
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mean and median survival times ranged between 8.2 and 57.4 months, and between 4.5 and 25 months, respectively. Patients whose data for mortality (98/794), morbidity (312/794), R0 resection (207/794), mean survival (544/794), median survival (90/794) were not reported are also shown in table 3.
Sperti/Berselli/Pedrazzoli
Table 3. Literature review of DP for body-tail pancreatic cancer
First author
Dalton [31] Johnson [32] Fabre [33]a Wade [34] Nakao [35] Kayahara [36] Ozaki [37]a Magistrelli [38] Burcharth [39] Shoup [40] Falconi [41] Lim [42] Wagner [43] Cleary [44] Sohn [45] Christein [46] Shimada [17] Moon [47] Strasberg [48] Goh [49] Murakami [50] Present series
Years
1963–1987 1972–1992 1982–1988 1987–1991 1981–1995 1970–1995 1980–1989 1988–1998 1977–2001 1983–2000 1990–1999 1991–1996 1993–2001 1988–1996 1984–1999 1987–2003 1990–2004 1995–2002 1999–2004 1992–2006 1990–2007 1989–2007
Total
Patients
Mortality
Morbidity
R0
Survival, months mean
median
26 13 128 14 30 39 36 10 13 57 25 16 29 7 52 66 97 23 21 30 34 49
0 0 11 (9.0) 3 (21.0) 2 (6.7) NR NR 0 1 (7.6) 0 0 NR 1 (3.4) NR 1 (1.9) 0 0 0 0 1 (3.3) 0 1 (2.0)
NR 2 (15) 41 (32) 6 (44) NR NR NR 3 (33) 7 (54) NR NR NR 5 (16) NR 13 (25) 31 (47) NR 5 (21) 11 (52) 6 (20) 11 (32) 13 (26)
NR NR NR NR 17 (57) 14 (36) 36 (100) NR 10 (77) 41 (72) 15 (60) NR 19 (66) NR 42 (80) 52 (79) 59 (61) 15 (65) 18 (86) 20 (67) 19 (56) 32 (65)
NR 19.1 8.2 21.5 NR NR NR NR 36.8 NR NR NR NR 57.4 NR NR NR NR NR NR NR 36.6
10.0 13.0 4.5 NR NRb 6.8c 16.7 NRd 12.9 15.9 15.5 21.7 NR NRe 12.0 15.5 25.0 19.7 21.0 15.0 14.0 12.0
794
21/696 (3.0%) NR: 98
154/482 (32%) NR: 312
409/587 (69.7%) NR: 207
NR: 544
NR: 90
Fig ures in parentheses indicate percentages. NR = Not reported. a Multicenter study. b Five-year survival: 6.7%. c R1 and R2 included. d Five-year survival: 23%. e Five-year survival: 57%.
Potentially curative surgery remains the treatment of choice for body-tail pancreatic cancer [2, 17]. However, it is classified as unresectable by the UICC when the ‘tumor involves the celiac axis or the superior mesenteric artery’ [5]. After the first DP-CAR for body-tail pancreatic cancer performed by Nimura et al. [7] in 1976, only 90 patients emerged from a careful literature review [7–28] (table 2). Since there are no large series of DP-CAR for pancreatic cancer, we pooled our own findings with published reports in an attempt to draw some conclusions about the related surgical risk and long-term results. We first performed a DP-CAR in 1989, in a 41-year-old male patient with a pancreatic cancer involving the CA, stomach, transverse colon, left adrenal gland and kidney. He developed peritoneal metastases 8 months after sur-
gery and died 6 months later. We have included the procedure among the surgical options for the treatment of body-tail pancreatic cancer ever since. During the study period, 168 patients were referred for body-tail pancreatic cancer, 49 underwent DP, 5 DPCAR, and 114 were unresectable. Our resectability rate therefore rose from 29.2% (49/168) to 32.1% (54/168) thanks to DP-CAR. After pooling our own with data reported in the literature [9, 11, 12, 17, 19], we collected 621 patients with body-tail pancreatic cancer. One-hundred and eighty-two patients (29.3%) underwent DP, 42 (6.8%) DP-CAR and in 397 (63.9%) the cancers were unresectable. Therefore, the resectability rate for body-tail pancreatic cancer increased significantly from 29.3 to 36.1% thanks to DP-CAR. Our morbidity rate was quite high (80%), but only 2 of our 5 patients had complications severe enough to prolong their hospital stay. The mean morbidity rate of 40.6%
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Discussion
495
(range 0–100%) after DP-CAR (table 2) was much higher than after DP (mean 32.0%, range 15–54%). Furthermore, our median hospital stay was much longer after DP-CAR (33.6 days) than after DP (14 days). Although DP-CAR is more demanding than DP from the technical point of view, our mortality rate was nil and was in line with other reports (mean 2.1%, range 0–50%; table 2). The mortality rate was the same for DP (mean 3.0%, range 0–21%; table 3). We performed a tangential resection of the portal vein in one of our 5 patients, as in 31/78 patients (39.7%) reported in the literature [7–16, 18–22, 24–26, 28]. The mortality rate after combined CA and portal vein resection was 2/31 patients (6.5%), while it was 0/47 patients after CA resection alone; thus, associating portal vein resection with DP-CAR increases the related mortality rate. The main concern for surgeons performing a DP-CAR is the adequacy of the blood supply to the liver via the superior mesenteric artery and the pancreatic arcades. Konishi et al. [11] reported several complications, such as liver necrosis, liver abscess, gallbladder necrosis and cholecystitis with DP-CAR. Several authors [11, 16, 18–20, 24] reported a transient, moderate elevation of hepatic enzymes, with no signs of clinically significant hepatic ischemia. In our experience, as in the more recently published series, carefully evaluating the pulsatility of the proper hepatic artery after occluding the CA and the CHA proximal to the gastroduodenal artery prevented any severe complications. Proper hepatic artery blood flow after CA and CHA clamping can be assessed by palpation, by monitoring hepatic venous hemoglobin oxygen saturation [12], by Doppler ultrasound [21], or by fluorescein test with Wood’s lamp [25]. If inadequate, the arterial blood flow was reconstructed by reimplantation of the CHA or left gastric artery to celiac trunk [16, 25], or by arterial [11, 18, 27, 28] or vein [12, 23, 27] grafts in one of our patients and 13/74 patients (17.6%) reported in the literature. If the surgical risk related to the DP-CAR is considered excessive, the procedure should be abandoned [15, 19]. To prevent ischemia-related complications, Hirano et al. [18] routinely performed a preoperative coil embolization of the CHA. Intractable abdominal and/or back pain due to advanced body-tail pancreatic cancer severely affects patients’ quality of life. Medical treatment with acetaminophen, NSAIDs and/or opioid drugs is often unsuccessful and complete pain relief is difficult to achieve even with the celiac plexus block. In our experience, one of the main achievements of DP-CAR was the control of severe pain in all 5 patients. Unfortunately, many authors do not re496
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port on their patients’ pain [7–9, 11, 12, 15–17, 20, 22–24, 26], while complete, or near-complete pain relief was achieved in 24 of 25 patients (96%) mentioned in reports dealing with this aspect [10, 13, 14, 18, 19, 21, 25, 27, 28] (table 2). Postoperative diarrhea requiring the prolonged administration of antidiarrheal drugs is an adverse effect of complete resection of the celiac plexus and ganglia, and one of the main concerns after the extended retroperitoneal dissection associated with DP-CAR. Here again, many authors sadly do not mention any pre- and/or postoperative diarrhea [7, 9, 12, 13, 15–17, 20–27]. Overall, it occurred in 18/43 patients (table 2). It was mild, however, and easily controlled with antidiarrheal therapy. An R0 resection was obtained in 3 of our 5 patients, the others being one R1 and one R2 resection. The overall R0 resection rate reported in the literature for DP-CAR was 71.2% (37/52), with 13 R1 (25%) and 2 R2 (3.8%; table 2). These results are much the same as for DP, with an R0 resection rate of 409/587 (69.7%, range 36–100%; table 3). Therefore DP-CAR can be performed with an acceptable radicality. However, careful patient selection should avoid difficult and risky R2 DP-CAR being performed instead of radiation and celiac plexus blockade in patients with a limited life expectancy. DP-CAR is an extended DP designed to obtain clear margins in a more advanced, otherwise unresectable, body-tail pancreatic cancer. In a review of 33,752 pancreatic cancers identified through the SEER registry, Artinyan et al. [51] reported a significantly higher rate of metastatic disease (67 vs. 36%, p ! 0.001) and a significantly lower rate of cancer-directed surgery (16 vs. 30%, p ! 0.001) for body-tail pancreatic cancer than for disease in the head of the pancreas. The shorter survival of patients with body-tail pancreatic cancers ‘may be potentially related to the extent of lymphadenectomy in body-tail patients undergoing curative resection’ [51], which further suggests the usefulness of an extended DP. All our 5 patients died after 8, 10, 10, 14 and 27 months. Our median survival after DP was not very different (12.0 months), while the mean survival was much longer (36.6 months) and the 5-year survival much higher (DP 12.2%; DP-CAR 0%). The mean and median survival times reported for 66 of 89 patients treated with DP-CAR (table 2) were 18.5 and 13 months, respectively. The mean survival after DP was only reported by a few other authors [32– 34, 39, 44] and ranged between 8.2 [33] and 57.4 [44] months, while the median survival ranged between 4.5 [33] and 25 months [17] (table 3). En bloc resection of the Sperti/Berselli/Pedrazzoli
surrounding structures involved, including the CA, to completely extirpate all macroscopic disease may consequently be worthwhile in selected patients, although long-term survivors are rare. Adjuvant treatment was given to 4/5 of our patients and 12/67 patients reported in the literature [19, 21, 22, 25]. IORT was also applied in 3 patients [13, 15] and neoadjuvant treatment was given in 7 [23, 26, 28]. Therefore, only 26/82 patients received some extra treatment before, during or after surgery. Such a limited experience, and with different treatments, prevents any conclusions from being drawn. Neoadjuvant chemoradiotherapy is claimed to be useful for a better local control of the disease and to avoid the need for complex surgical procedures in patients with an extremely aggressive tumor that progresses during neoadjuvant treatment [23, 26, 28]. Be that as it may, we need well-designed prospective, randomized studies on body-tail pancreatic cancer, possibly including DP-CAR. Chemoradiotherapy is the alternative treatment for candidates for DP-CAR, whose pancreatic cancer is unresectable without en bloc resection of the CA. According to a systematic review performed by Azria et al. [52], the reported median survival for locally advanced pancreatic cancer treated with chemoradiotherapy ranges between 6.7 and 14.5 months. Most of the studies reporting a longer survival (12–14.5 months) were performed more recently, using more effective chemoradiotherapeutic regimens. On the other hand, the median survival for the
more recent series of DP-CAR was 14 [25], 17 [17, 26], 18 [18], and 19 [19] months. We can conclude that a longer survival can probably be achieved with DP-CAR (with adjuvant or neoadjuvant treatment) than with chemotherapy or chemoradiotherapy alone for locally advanced body-tail pancreatic cancer.
Conclusions
DP-CAR can be performed safely by an experienced surgical team and may improve survival for carefully selected patients with locally advanced pancreatic cancer. It increases the resectability rate of body-tail pancreatic cancer, and should be included among the ‘extended’ DPs. Whether neoadjuvant chemotherapy or chemoradiotherapy should be performed before DP-CAR in selected patients remains to be established on the strength of prospective randomized trials. An important collateral achievement of DP-CAR is excellent pain control in most patients.
Acknowledgements The authors gratefully acknowledge Tania Lazzarin and Simona Callegari for helping to supply the clinical material and prepare the manuscript.
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40 Shoup M, Conlon KC, Klimstra D, Brennan MF: Is extended resection for adenocarcinoma of the body and tail of the pancreas justified? J Gastrointest Surg 2003;7:946–952. 41 Falconi M, Mantovani W, Bettini R, Talamini G, Bassi C, Cascinu S, Oliani C, Pederzoli P: Carcinoma of pancreatic body and tail: are there improvements in diagnosis and treatment modalities over the past decade? Dig Liver Dis 2003;35:421–427. 42 Lim J, Chien MW, Earle CC: Prognostic factors following curative resection for pancreatic adenocarcinoma. Ann Surg 2003; 237: 74–85. 43 Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Büchler MW: Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:586–594. 44 Cleary SP, Gryfe R, Guindi M, Greig P, Smith L, Mackenzie R, Strasberg S, Hanna S, Taylor B, Langer B, Gallinger S: Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg 2004;198:722–731. 45 Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, Coleman J, Hruban RH, Lillemoe KD: Resected adenocarcinoma of the pancreas – 616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000; 4:567–579. 46 Christein JD, Kendrick ML, Iqbal CW, Nagorney DM, Farnell MB: Distal pancreatectomy for resectable adenocarcinoma of the body and tail of the pancreas. J Gastrointest Surg 2005;9:922–927. 47 Moon HJ, An JY, Heo JS, Choi SH, Joh JW, Kim YI: Predicting survival after surgical resection for pancreatic ductal adenocarcinoma. Pancreas 2006;32:37–43. 48 Strasberg SM, Linehan DC, Hawkins WG: Radical antegrade modular pancreatosplenectomy procedure for adenocarcinoma of the body and tail of the pancreas: ability to obtain negative tangential margins. J Am Coll Surg 2007;204:244–249. 49 Goh BKP, Tan YM, Cheow PC, Chung YFA, Chow PKH, Wong WK, Ooi LLPJ: Outcome of distal pancreatectomy for pancreatic adenocarcinoma. Dig Surg 2008;25:32–38. 50 Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Ohge H, Sueda T: Impact of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for adenocarcinoma of the body or tail of the pancreas. J Gastrointest Surg 2009;13:85–92. 51 Artinyan A, Soriano PA, Prendergast C, Low T, Ellenhorn JDI, Kim J: The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB 2008;10:371–376. 52 Azria D, Seblain-El-Guerche C, Girard N, Hennequin C, Huguet F: Intérêt de la chimioradiothérapie dans la prise en charge des adénocarcinomes du pancréas localement avancés: revue systematique. Bull Cancer 2008;95:1116–1130.
Sperti/Berselli/Pedrazzoli
Received: July 20, 2009 Accepted after revision: January 6, 2010 Published online: August 19, 2010
Distal Pancreatectomy for Body-Tail Pancreatic Cancer: Is There a Role for Celiac Axis Resection? Cosimo Sperti Mattia Berselli Sergio Pedrazzoli IV Surgical Clinic, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy
Key Words Advanced pancreatic cancer ⴢ Distal pancreatectomy ⴢ Celiac axis resection ⴢ Common hepatic artery ⴢ Extended resection ⴢ Modified Appleby operation
Abstract Background/Aims: Body-tail pancreatic cancer is an aggressive disease with a low resectability rate and a poor prognosis. Celiac axis invasion usually contraindicates resection. The aim of this study was to analyze the feasibility of distal pancreatectomy (DP) with celiac axis resection (DP-CAR) for locally advanced body-tail pancreatic cancer. Methods: All DPs performed between January 1989 and December 2007 were considered. DP and DP-CAR were reviewed for pre-, intra- and postoperative data. An extensive, detailed literature review on DP and DP-CAR was also performed. Results: DP was performed in 49 of our patients, and 745 cases were retrieved from the literature. The overall morbidity and mortality rates were 32.0 and 3.0%, respectively. We performed DPCAR in 5 patients with no mortality but 80% morbidity. A further 90 patients were retrieved from the literature. Arterial reconstruction was needed in 1/5 of our patients and in 13/90 of patients in the literature. Collaterals from superior mesenteric artery maintained adequate hepatic artery blood flow in the remaining 81 patients. The overall morbidity and mortality rates were 40.6 and 2.1%, respectively. The
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median survival ranged between 4.5 and 25 months after DP and was 13 months after DP-CAR. Conclusions: DP-CAR improves resectability without increasing the mortality rate. The complication rate after DP-CAR was higher than after DP, but still within the range of extended DP. DP-CAR should be considered for the inclusion among the ‘extended’ procedures for the treatment of body-tail pancreatic cancers invading the celiac axis. Copyright © 2010 S. Karger AG, Basel and IAP
Introduction
Patients with resectable pancreatic cancer account for only 15–20% of all adenocarcinomas of the pancreas [1, 2]. Unresectability is usually due to encasement of the celiac axis (CA), or superior mesenteric artery or distant metastases, identified either by high-quality computed tomography (CT) [3] or intraoperatively [4]. This is often the case in body-tail pancreatic cancer, which tends to be found in a more advanced stage, when the tumor’s extension frequently makes its resection impossible or pointless [2]. One of the reasons why body-tail pancreatic cancer may be unresectable is due to the encasement of the CA and of the origin of the common hepatic artery (CHA), usually associated with severe pain. Cancer invading the CA is considered a locally advanced, unresectProf. Sergio Pedrazzoli, MD, FACS Department of Medical and Surgical Sciences Clinica Chirurgica IV, Via Giustiniani 2 IT–35128 Padova (Italy) Tel. +39 049 821 8827, Fax +39 049 821 8829, E-Mail sergio.pedrazzoli @ unipd.it
able, primary tumor [3, 5]. En bloc resection of the CA and CHA can theoretically improve the resectability of body-tail pancreatic cancer, however. Appleby, a Canadian surgeon, was the first to describe a distal pancreatectomy (DP) with CA resection (DP-CAR) and en bloc resection of the stomach, spleen, left pancreas, and CHA in a patient with gastric cancer in 1953 [6]. Nimura et al. [7] performed the first DPCAR in a patient with body-tail pancreatic cancer in 1976. To date, DP-CAR for the surgical treatment of body-tail pancreatic cancer has been reported in a limited number of patients, mainly by Far Eastern authors [7–22], while experience with this operation in Western countries is limited and more recent [23–28]. The indication for DP-CAR was recently extended to patients without any direct invasion of the CA to increase the radical resection (R0) rate for advanced body-tail pancreatic cancer [18]. The inclusion of DP-CAR in the surgical armamentarium is still widely debated because its efficacy in terms of postoperative complications and mortality and survival rates has yet to be clearly elucidated. This paper reports our experience with DP and DPCAR, for body-tail pancreatic cancer, analyzing postoperative outcome, pain control, and overall and diseasefree survival. An extensive, detailed review was also conducted on cases of DP and DP-CAR for pancreatic cancer reported in the English literature.
Lymphadenectomy includes nodes of the CA, splenic artery, hilum of the spleen, inferior border of the body-tail and anteriorsuperior region of the CHA [30]. Distal Pancreatectomy with Celiac Axis Resection After performing a wide upper midline incision and confirming that disease is localized, the CHA, the gastroduodenal artery and the mesenteric-portal confluent are exposed to verify the feasibility of the procedure. A DP-CAR is contraindicated when any invasion of the CHA near to the origin of the gastroduodenal artery, of the CA at its origin from the aorta, and of para-aortic region is found. The superior mesenteric artery is skeletonized on its anterior and left side from the inferior pancreaticoduodenal artery to its origin from the aorta, carefully preserving the pancreaticoduodenal arterial arcade to maintain adequate hepatic artery blood flow. The CA is exposed at its origin from the aorta on its right side, eventually transecting the left gastric artery, and occluded with a Cooley clamp. CHA is also occluded distal to the tumor, but proximal to the gastroduodenal artery, and the pulses in the right and left hepatic arteries are verified. If inadequate pulses are found, the procedure implies the need of revascularization of the CHA. The CA and the CHA are then transected, and the pancreas is divided along the right side of the portal vein. The right gastroepiploic and right gastric artery are preserved, together with the whole stomach. The spleen and the pancreatic bodytail are then removed along with the left adrenal gland if necessary. Resection of the mesenteric-portal confluent and/or of other organs involved is performed if necessary. Literature Review A focused literature review was conducted on the surgical treatment of body-tail pancreatic cancer, using the Medline database for studies published up until June 2009, and comparing clinical data and outcomes following DP and DP-CAR. The latest search was conducted in June 2009. References mentioned in articles were also checked offline.
Materials and Methods Personal Experience All patients undergoing DP for pancreatic cancer between January 1989 and December 2007 were reviewed and classified as DP or DP-CAR. Details were retrospectively collected on patients’ age, sex and preoperative clinical data, tumor imaging findings, the characteristics of the surgical specimen and histological findings, postoperative morbidity and mortality rates, postoperative outcome, pain control, follow-up and survival. Tumors were staged according to the pTNM (UICC) classification [5]. Pancreatic fistula was defined according to the criteria of Yeo et al. [29]. Follow-up included physical examination, routine laboratory tests, determining tumor markers (CEA and CA 19–9), and abdominal ultrasound and/or CT every 3 months. FDG-PET or PET/CT was performed where clinically indicated. Distal Pancreatectomy The pancreas is transected along the right border of the mesenteric-portal confluence; the splenic artery is transected at its origin from the CA. Resection of the mesenteric-portal confluent, and/or other organs involved is performed whenever necessary.
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Results
Between January 1989 and December 2007, 168 patients were referred to our department for body-tail pancreatic cancer. Fifty-four underwent surgical treatment: 49 had a DP and 5 had a DP-CAR. Among the 49 who underwent DP, there were 23 males and 26 females with a median age of 63.8 years (range 41–87). Severe pain was reported before surgery by 38 patients (77.6%). The median operating time was 231 min (range 180–325) and the mean and median hospital stay was 16.7 and 14 days, respectively (range 6–45). Thirteen patients (26%) had postoperative complications, including 6 pancreatic fistulas (12.2%). One patient (2%) died of myocardial infarction. R0 was achieved in 32 patients (65%), R1 in 13, and R2 in 4 patients. The mean and median survival times were 36.6 and 12.0 months (range 0–96), with a 12.2% 5-year survival rate. Sperti/Berselli/Pedrazzoli
Table 1. Patients’ characteristics
Patient Age/ No. sex
Symptoms
Preoperative tumor staging
Size mm
Resected structures
Morbidity
Treatment of complications
R
AGR, TC, LN and LA
colonic fistula
reoperation (83rd R0 postoperative day)
no
no
R1
postoperative bleeding
reoperation
R2
1
41/M back pain
vascular (CA, splenic vein), 60 gastric and renal encasement
2
70/M abdominal pain
vascular encasement (CA, splenic vein)
25
3
58/M abdominal and back vascular encasement pain/weight loss/diabetes (CA, splenic vein)
30
4
72/F
abdominal and back pain/weight loss
vascular encasement (CA, splenic artery)
40
pancreatic fistula radiological drain
R0
5
73/F
abdominal and back pain vascular encasement (CA, splenic artery)
40
pancreatic fistula radiological drain
R0
MPVR
AGR = Atypical gastric resection; TC = transverse colon resection; LN = left nephrectomy; LA = left adrenalectomy; MPVR = mesenteric-portal vein resection.
Details of the 5 patients who underwent DP-CAR are reported in table 1. All 5 patients had poorly-controlled severe pain before the operation. CT had detected CA invasion in all 5 patients and retroperitoneal invasion in 4. The origin and at least 1 cm of the CA appeared to be unaffected by tumor invasion in all patients. After excluding any distant metastases, patients underwent surgical exploration without neoadjuvant chemotherapy or radiotherapy. Three patients (table 1, No. 2, 4 and 5) underwent DP-CAR alone, while a partial gastric and colonic resection, together with left adrenalectomy, nephrectomy, and reconstruction of the CHA, was also performed in one (table 1, No. 1); the 5th patient (table 1, No. 3) had DP-CAR plus tangential resection of the mesenteric portal confluent. The median operating time was 233 min (range 190–285) and the median hospital stay was 33.6 days (range 14–92). There were no postoperative deaths, while postoperative complications occurred in 80% of patients (table 1). One developed a colonic fistula due to colectomy and was reoperated 83 days after the DP-CAR. One (table 1, No. 3) required emergency reoperation within 24 h of the DP-CAR for intraperitoneal bleeding. Two patients developed a lowoutput pancreatic fistula that closed spontaneously without prolonging their hospital stay. At discharge, none of the patients needed analgesics or complained of severe diarrhea. An R0 resection was achieved in 3 patients, an R1 in one, and an R2 in one (table 1). Four patients had a G2 (moderately differentiated) and one (No.
3) had a G3 (poorly differentiated) pancreatic cancer. Lymph node metastases were found in all but one (No. 1) of the patients. Median disease-free survival was 8 months (range 4–13), and median overall survival was 10 months (range 8–27). Two patients (No. 1 and 3) developed peritoneal metastases and died 14 and 10 months after DP-CAR, respectively. Liver metastases developed in one patient (No. 2) and lung metastases in another (No. 4): they died 10 and 8 months after DP-CAR, respectively. One patient (No. 5) underwent excision of a tumor relapse at the wound site of laparotomy 13 months after DP-CAR. Two months later, FDG-PET/CT revealed tumor recurrence in the pancreatic bed. The patient was given chemotherapy and stereotactic radiotherapy, and died of disseminated disease 27 months after primary resection. No pain or severe diarrhea relapsed in our patients until their tumor recurred. Adjuvant treatment was given to 3/5 patients after DPCAR and to 33/48 survivors (68.8%) after DP. The outcome of the literature review on DP-CAR is shown in table 2. The overall mortality and morbidity rates were 2.1 and 40.6%, respectively. The R0 resection rate was 71.2%, pain control was achieved in 97% of 32 patients (13 further patients were pain free preoperatively), postoperative diarrhea was registered in 41.9% of 43 patients and the mean and median survival times were 18.5 and 13 months (range 2–156), respectively, with a 3.9% 5-year survival (3/77 patients). Patients whose data
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493
Table 2. Literature review of DP-CAR for pancreatic cancer
First author
Year
PaDeaths Mortients bidity
R0
dead
Nimura [7] Imaizumia Fujitaa Yamamoria Ozaki [8] Mayumi [9] Kimura [10] Konishi [11] Miyakawa [12]
1976 1979 1987 1996 1996 1997 1997 2000 2002
1 1 4 1 1 6 1 4 8
0 0 2 0 0 0 0 0 0
NR NR NR NR NR 2 0 1 3
NR NR NR NR NR NR 1 1 NR
Sasson [23] Yamaguchi [13] Liu [14] Hirai [15] Lin [16] Makary [24] Gagandeep [25] Shimada [17] Hirano [18]c
2002 2003 2003 2005 2005 2005 2006 2006 2007
4 2 1 1 1 1 3 12 23
0 0 0 0 0 0 0 0 0
NR 1 0 NR 0 0 1 NR 11
NR 0 NR 0 NR 1 3 NR 21
Hishinuma [19]
2007
7
0
2
4
Wu [20] Chen [21] Stitzenberg [26] Bonnet [27] Machado [28] Mizutani [22] Present series
2007 2008 2008 2009 2009 2009
1e 1 2 1 1 2 5
0 0 0 NR 0 0 0
1 0 2 NR 0 0 4
NR 1 0 NR NR 2 3
95
2/94 28/69 (2.1%) (40.6%) NR: 26
Total
Survival, months
37/52 (71.2%) NR: 43
alive
NR 3 4, 7
4, 6, 9, 10, 31 5, 10, 14, 18 7, 7, 7, 9, 11, 20, 21, 43 10, 13 8, 14 8 NR 30 NR
11 156 59 18
22, 27
14, 14, 34 median: 17b 4, 5, 6, 10, 11, 14, 16, 18, 21 4, 13, 17, 19, 21, 42, 78 2 11 17, 17 NR 13 6g 8, 10, 10, 14, 27 mean: 18.3 median: 13
1, 2, 4, 5, 5, 11, 18, 18, 22, 27, 32, 35, 40, 62
NRf 8
Pain control
Diarrhea
NR NR NR NR NR NR 1/1 NR NR
NR NR NR NR 1/1 NR 0/1 3/4 NR
NR 2/2 1/1 NR NR NR 3/3 NR 10/10d
NR NR 0/1 NR NR NR NR NR 8/23
6/7
5/7
NR 1/1 NR 1/1 1/1 NR 5/5
NR NR NR NR 0/1 NR 1/5
31/32 (97%) NR: 50d
18/43 (41.9%) NR: 52
NR = Not reported. a Reported by Kimura et al. [10]. b Zero survivors at 2 years. c Survival of each of the 23 patients kindly communicated by the author. d Thirteen patients pain free preoperatively. e Sarcomatoid carcinoma. f Seven Appleby’s procedures, but only one for pancreatic cancer; one of seven still alive. g Not related to pancreatic cancer.
for morbidity (26/95), R0 resection (43/95), pain control (50/95) and diarrhea (52/95) were not reported are also shown in table 2. The outcome of the literature review on DP [17, 31–50] is shown in table 3. The overall mortality and morbidity rates were 3.0% (range 0–21%) and 32% (range 15–54%), respectively. The R0 resection rate was 69.7%, and the 494
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mean and median survival times ranged between 8.2 and 57.4 months, and between 4.5 and 25 months, respectively. Patients whose data for mortality (98/794), morbidity (312/794), R0 resection (207/794), mean survival (544/794), median survival (90/794) were not reported are also shown in table 3.
Sperti/Berselli/Pedrazzoli
Table 3. Literature review of DP for body-tail pancreatic cancer
First author
Dalton [31] Johnson [32] Fabre [33]a Wade [34] Nakao [35] Kayahara [36] Ozaki [37]a Magistrelli [38] Burcharth [39] Shoup [40] Falconi [41] Lim [42] Wagner [43] Cleary [44] Sohn [45] Christein [46] Shimada [17] Moon [47] Strasberg [48] Goh [49] Murakami [50] Present series
Years
1963–1987 1972–1992 1982–1988 1987–1991 1981–1995 1970–1995 1980–1989 1988–1998 1977–2001 1983–2000 1990–1999 1991–1996 1993–2001 1988–1996 1984–1999 1987–2003 1990–2004 1995–2002 1999–2004 1992–2006 1990–2007 1989–2007
Total
Patients
Mortality
Morbidity
R0
Survival, months mean
median
26 13 128 14 30 39 36 10 13 57 25 16 29 7 52 66 97 23 21 30 34 49
0 0 11 (9.0) 3 (21.0) 2 (6.7) NR NR 0 1 (7.6) 0 0 NR 1 (3.4) NR 1 (1.9) 0 0 0 0 1 (3.3) 0 1 (2.0)
NR 2 (15) 41 (32) 6 (44) NR NR NR 3 (33) 7 (54) NR NR NR 5 (16) NR 13 (25) 31 (47) NR 5 (21) 11 (52) 6 (20) 11 (32) 13 (26)
NR NR NR NR 17 (57) 14 (36) 36 (100) NR 10 (77) 41 (72) 15 (60) NR 19 (66) NR 42 (80) 52 (79) 59 (61) 15 (65) 18 (86) 20 (67) 19 (56) 32 (65)
NR 19.1 8.2 21.5 NR NR NR NR 36.8 NR NR NR NR 57.4 NR NR NR NR NR NR NR 36.6
10.0 13.0 4.5 NR NRb 6.8c 16.7 NRd 12.9 15.9 15.5 21.7 NR NRe 12.0 15.5 25.0 19.7 21.0 15.0 14.0 12.0
794
21/696 (3.0%) NR: 98
154/482 (32%) NR: 312
409/587 (69.7%) NR: 207
NR: 544
NR: 90
Fig ures in parentheses indicate percentages. NR = Not reported. a Multicenter study. b Five-year survival: 6.7%. c R1 and R2 included. d Five-year survival: 23%. e Five-year survival: 57%.
Potentially curative surgery remains the treatment of choice for body-tail pancreatic cancer [2, 17]. However, it is classified as unresectable by the UICC when the ‘tumor involves the celiac axis or the superior mesenteric artery’ [5]. After the first DP-CAR for body-tail pancreatic cancer performed by Nimura et al. [7] in 1976, only 90 patients emerged from a careful literature review [7–28] (table 2). Since there are no large series of DP-CAR for pancreatic cancer, we pooled our own findings with published reports in an attempt to draw some conclusions about the related surgical risk and long-term results. We first performed a DP-CAR in 1989, in a 41-year-old male patient with a pancreatic cancer involving the CA, stomach, transverse colon, left adrenal gland and kidney. He developed peritoneal metastases 8 months after sur-
gery and died 6 months later. We have included the procedure among the surgical options for the treatment of body-tail pancreatic cancer ever since. During the study period, 168 patients were referred for body-tail pancreatic cancer, 49 underwent DP, 5 DPCAR, and 114 were unresectable. Our resectability rate therefore rose from 29.2% (49/168) to 32.1% (54/168) thanks to DP-CAR. After pooling our own with data reported in the literature [9, 11, 12, 17, 19], we collected 621 patients with body-tail pancreatic cancer. One-hundred and eighty-two patients (29.3%) underwent DP, 42 (6.8%) DP-CAR and in 397 (63.9%) the cancers were unresectable. Therefore, the resectability rate for body-tail pancreatic cancer increased significantly from 29.3 to 36.1% thanks to DP-CAR. Our morbidity rate was quite high (80%), but only 2 of our 5 patients had complications severe enough to prolong their hospital stay. The mean morbidity rate of 40.6%
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Discussion
495
(range 0–100%) after DP-CAR (table 2) was much higher than after DP (mean 32.0%, range 15–54%). Furthermore, our median hospital stay was much longer after DP-CAR (33.6 days) than after DP (14 days). Although DP-CAR is more demanding than DP from the technical point of view, our mortality rate was nil and was in line with other reports (mean 2.1%, range 0–50%; table 2). The mortality rate was the same for DP (mean 3.0%, range 0–21%; table 3). We performed a tangential resection of the portal vein in one of our 5 patients, as in 31/78 patients (39.7%) reported in the literature [7–16, 18–22, 24–26, 28]. The mortality rate after combined CA and portal vein resection was 2/31 patients (6.5%), while it was 0/47 patients after CA resection alone; thus, associating portal vein resection with DP-CAR increases the related mortality rate. The main concern for surgeons performing a DP-CAR is the adequacy of the blood supply to the liver via the superior mesenteric artery and the pancreatic arcades. Konishi et al. [11] reported several complications, such as liver necrosis, liver abscess, gallbladder necrosis and cholecystitis with DP-CAR. Several authors [11, 16, 18–20, 24] reported a transient, moderate elevation of hepatic enzymes, with no signs of clinically significant hepatic ischemia. In our experience, as in the more recently published series, carefully evaluating the pulsatility of the proper hepatic artery after occluding the CA and the CHA proximal to the gastroduodenal artery prevented any severe complications. Proper hepatic artery blood flow after CA and CHA clamping can be assessed by palpation, by monitoring hepatic venous hemoglobin oxygen saturation [12], by Doppler ultrasound [21], or by fluorescein test with Wood’s lamp [25]. If inadequate, the arterial blood flow was reconstructed by reimplantation of the CHA or left gastric artery to celiac trunk [16, 25], or by arterial [11, 18, 27, 28] or vein [12, 23, 27] grafts in one of our patients and 13/74 patients (17.6%) reported in the literature. If the surgical risk related to the DP-CAR is considered excessive, the procedure should be abandoned [15, 19]. To prevent ischemia-related complications, Hirano et al. [18] routinely performed a preoperative coil embolization of the CHA. Intractable abdominal and/or back pain due to advanced body-tail pancreatic cancer severely affects patients’ quality of life. Medical treatment with acetaminophen, NSAIDs and/or opioid drugs is often unsuccessful and complete pain relief is difficult to achieve even with the celiac plexus block. In our experience, one of the main achievements of DP-CAR was the control of severe pain in all 5 patients. Unfortunately, many authors do not re496
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port on their patients’ pain [7–9, 11, 12, 15–17, 20, 22–24, 26], while complete, or near-complete pain relief was achieved in 24 of 25 patients (96%) mentioned in reports dealing with this aspect [10, 13, 14, 18, 19, 21, 25, 27, 28] (table 2). Postoperative diarrhea requiring the prolonged administration of antidiarrheal drugs is an adverse effect of complete resection of the celiac plexus and ganglia, and one of the main concerns after the extended retroperitoneal dissection associated with DP-CAR. Here again, many authors sadly do not mention any pre- and/or postoperative diarrhea [7, 9, 12, 13, 15–17, 20–27]. Overall, it occurred in 18/43 patients (table 2). It was mild, however, and easily controlled with antidiarrheal therapy. An R0 resection was obtained in 3 of our 5 patients, the others being one R1 and one R2 resection. The overall R0 resection rate reported in the literature for DP-CAR was 71.2% (37/52), with 13 R1 (25%) and 2 R2 (3.8%; table 2). These results are much the same as for DP, with an R0 resection rate of 409/587 (69.7%, range 36–100%; table 3). Therefore DP-CAR can be performed with an acceptable radicality. However, careful patient selection should avoid difficult and risky R2 DP-CAR being performed instead of radiation and celiac plexus blockade in patients with a limited life expectancy. DP-CAR is an extended DP designed to obtain clear margins in a more advanced, otherwise unresectable, body-tail pancreatic cancer. In a review of 33,752 pancreatic cancers identified through the SEER registry, Artinyan et al. [51] reported a significantly higher rate of metastatic disease (67 vs. 36%, p ! 0.001) and a significantly lower rate of cancer-directed surgery (16 vs. 30%, p ! 0.001) for body-tail pancreatic cancer than for disease in the head of the pancreas. The shorter survival of patients with body-tail pancreatic cancers ‘may be potentially related to the extent of lymphadenectomy in body-tail patients undergoing curative resection’ [51], which further suggests the usefulness of an extended DP. All our 5 patients died after 8, 10, 10, 14 and 27 months. Our median survival after DP was not very different (12.0 months), while the mean survival was much longer (36.6 months) and the 5-year survival much higher (DP 12.2%; DP-CAR 0%). The mean and median survival times reported for 66 of 89 patients treated with DP-CAR (table 2) were 18.5 and 13 months, respectively. The mean survival after DP was only reported by a few other authors [32– 34, 39, 44] and ranged between 8.2 [33] and 57.4 [44] months, while the median survival ranged between 4.5 [33] and 25 months [17] (table 3). En bloc resection of the Sperti/Berselli/Pedrazzoli
surrounding structures involved, including the CA, to completely extirpate all macroscopic disease may consequently be worthwhile in selected patients, although long-term survivors are rare. Adjuvant treatment was given to 4/5 of our patients and 12/67 patients reported in the literature [19, 21, 22, 25]. IORT was also applied in 3 patients [13, 15] and neoadjuvant treatment was given in 7 [23, 26, 28]. Therefore, only 26/82 patients received some extra treatment before, during or after surgery. Such a limited experience, and with different treatments, prevents any conclusions from being drawn. Neoadjuvant chemoradiotherapy is claimed to be useful for a better local control of the disease and to avoid the need for complex surgical procedures in patients with an extremely aggressive tumor that progresses during neoadjuvant treatment [23, 26, 28]. Be that as it may, we need well-designed prospective, randomized studies on body-tail pancreatic cancer, possibly including DP-CAR. Chemoradiotherapy is the alternative treatment for candidates for DP-CAR, whose pancreatic cancer is unresectable without en bloc resection of the CA. According to a systematic review performed by Azria et al. [52], the reported median survival for locally advanced pancreatic cancer treated with chemoradiotherapy ranges between 6.7 and 14.5 months. Most of the studies reporting a longer survival (12–14.5 months) were performed more recently, using more effective chemoradiotherapeutic regimens. On the other hand, the median survival for the
more recent series of DP-CAR was 14 [25], 17 [17, 26], 18 [18], and 19 [19] months. We can conclude that a longer survival can probably be achieved with DP-CAR (with adjuvant or neoadjuvant treatment) than with chemotherapy or chemoradiotherapy alone for locally advanced body-tail pancreatic cancer.
Conclusions
DP-CAR can be performed safely by an experienced surgical team and may improve survival for carefully selected patients with locally advanced pancreatic cancer. It increases the resectability rate of body-tail pancreatic cancer, and should be included among the ‘extended’ DPs. Whether neoadjuvant chemotherapy or chemoradiotherapy should be performed before DP-CAR in selected patients remains to be established on the strength of prospective randomized trials. An important collateral achievement of DP-CAR is excellent pain control in most patients.
Acknowledgements The authors gratefully acknowledge Tania Lazzarin and Simona Callegari for helping to supply the clinical material and prepare the manuscript.
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