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Pancreatic anatomy in the era of extensive and less invasive surgery 289
Figure 21.2 View of autopsy cases after injection of three colors of dye into the vessels and ducts. (a) Anterior–inferior
pancreaticoduodenal artery (AIPDA). Anterior view of the fixed pancreatic head obtained from an autopsy case. The
embryologically dorsal primordium (anterior segment) has been removed along the embryological fusion plane. Following anterior
segmentectomy, the intrapancreatic bile duct (yellow arrowhead), the duct of Wirsung (asterisk), and the posterior segment
(embryologically ventral primordium) have been preserved. The anterior arcade of the pancreatic head consists of the
gastroduodenal artery (GDA, red arrowhead), the anterior–superior pancreaticoduodenal artery (ASPDA, black arrowhead), and the
anterior–inferior pancreaticoduodenal artery (AIPDA, white arrowheads). (b) Posterior–inferior pancreaticoduodenal artery (PIPDA).
Posterior view of the fixed pancreatic head obtained from an autopsy case. There are four branches of the superior mesenteric artery
(SMA, white arrow): the first jejunal artery (white arrowhead), the anterior–inferior pancreaticoduodenal artery (AIPDA, yellow
arrowhead), the posterior–superior pancreaticoduodenal artery (PSPDS, yellow arrow) and the posterior–inferior pancreaticoduodenal
artery (PIPDA, black arrowhead). In this case, the four arteries branched off the SMA independently.
PD [4]. The artery first approach has been described for
laparoscopic PD and entails early dissection and assessment of the tissue adjacent to the SMA. This approach is
facilitated by the laparoscopic view below the head of the
pancreas after kocherization. To minimize blood loss and
risk for postoperative bleeding, it is important that pancreatic surgeons identify and control the inflow arteries to
the pancreatic head coming off the SMA, as mentioned
earlier.
Another important factor in the arterial anatomy of the
pancreas is that there is always a small branch from the
SMA to the body of the pancreas. This pancreatic body
artery must be divided to remove the left side of the
pancreas at the level of the portal vein. In the majority
of cases, this arterial branch becomes the transverse
pancreatic artery [5]. A possible variation is a communication of this artery with the dorsal pancreatic artery
(DPA).
Aberrant hepatic arteries from the SMA
Aberrant right hepatic artery (RHA) from the SMA is
reported in 15–25% of patients [6,7]. Aberrant RHA
consists of replaced RHA (singular artery from the
SMA) and accessory RHA (an additional RHA coming
off the SMA). A replaced RHA often travels behind the
portal vein and the pancreatic head through Calot’s
triangle. Any anatomical variation in the hepatoduodenal
ligament should be carefully evaluated before surgery.
The most dangerous variation would be a case in
which the RHA is a re plac ed artery coming off the
gastroduodenal artery (GDA), where the GDA cannot
be divided at the typical location close to the common
hepatic artery (CHA).
21.2.1.2 Celiac axis
The celiac axis has several branches, including the bilateral phrenic arteries, left gastric artery (LGA), splenic
290 Chapter 21
Figure 21.3 Intraoperative identification of the branches from
the superior mesenteric artery (SMA). After division of the
right side of the nerve plexus of the SMA, the inferior
pancreaticoduodenal artery (IPDA, A), the posterior–inferior
pancreaticoduodenal artery (PIPDA, B), the anterior–inferior
pancreaticoduodenal artery (AIPDA, C), and the first jejunal
artery (D) were taped. In the “artery first” approach, the IPDA
and the first jejunal artery should be ligated, which will
decrease the blood supply to the pancreatic head.
artery (SpA), common hepatic artery (CHA), dorsal pancreatic artery (DPA), aberrant hepatic artery, inferior
phrenic arteries, and others.
The CeA is surrounded by the celiac nerve plexus,
which in case of tumor infiltration can be the source of
significant cancer-related pain. The root of the DPA can be
the trunk of the CeA, CHA or SpA [5]. The first major
branch of the CHA is usually the GDA, at which point the
CHA becomes the proper hepatic artery (PHA). The GDA
branches off the right gastroepiploic artery (RGA). After
this branching, the GDA becomes the anterior–superior
pancreaticoduodenal artery (ASPDA), which has a communication with the IPDA. This arterial communication
creates an anterior pancreatic arcade (see Figure 21.2a).
The origin of the posterior–superior pancreaticoduodenal
artery (PSPDA) can be the GDA or PHA, or it may be an
aberrant hepatic artery. The PSPDA travels behind the
pancreatic head toward the major papilla, and it may give
off additional small branches to the duodenum. The
communication of the PSPDA and PIPDA creates a posterior pancreatic arcade (see Figure 21.2b). In patients
with median arcuate ligament syndrome, the root of the
CeA is compressed by the ligament. This can be a critical
finding when performing a pancreaticoduodenectomy
since in these cases the hepatic arterial flow might be
insufficient after resection of the pancreatic head. Division of the arcuate ligament will restore the flow of the
CeA [8].
Maintenance of hepatic arterial inflow during
distal pancreatectomy with en bloc celiac axis
resection (DP-CAR) (see Videos 24 and 25)
Surgical resection of pancreatic cancer involving the
celiac axis is controversial. However, recent reports
have shown a five-year survival rate of 42% in patients
with pancreatic invasive cancer undergoing DP-CAR, a
modified Appleby’s procedure [9]. In gastric cancer
surgery, it had been known that total gastrectomy combined with en bloc resection of the celiac axis enables
complete cancer removal with the so-called Appleby’s
procedure [10]. Application of Appleby’s procedure to
pancreatic cancer should be done only in select circumstances, because of the higher morbidity and mortality
rate in comparison with conventional DP [11].
During DP-CAR, the roots of the SMA and CeA should
be identified. After clamping the celiac axis from the
SMA via the pancreatic head arcades, hepatic arterial
flow should be confirmed before resection of the CeA
(Figure 21.4a). After completion of DP-CAR, the nerve
plexus of SMA is dissected, while the stump of the CeA is
exposed on the dissecting plane (Figure 21.4b).
21.2.2 Venous anatomy
The venous anatomy of the pancreatic head may vary
widely from patient to patient. However, there are
certain common features and variations that are
more likely to occur. T he major portal venous tributaries to the portal system consist of the portal vein
(PV), s uperior mesenteric vein (SMV), splenic vein
(SpV), superior mesenteric vein (SPV), Henle’sgastrocolic trunk (GCT), middle colic vein (MCV), inferior
mesenteric vein ( IMV), jejunal veins, left gastric vein
(coronary vein), and right gastric vein. The venous
drainage of the pancreatic head runs partly independent from the arter ial tributaries. For further reading,
Douglass et al. nicely summarize the detailed anatomy
of the pancreatic venous tributaries [12].
The key branches are the PV, SpV, and SMV, and the
most frequent anatomical variations are as follows.
Pancreatic anatomy in the era of extensive and less invasive surgery 291
Figure 21.5 Posterior view of the autopsy cases after injection
of three colors of dye into the vessels and ducts. The posterior–
superior pancreaticoduodenal vein (PSPDV) joins the posterior
wall of the portal vein, and the posterior–inferior
pancreaticoduodenal vein (PIPDV) joins the posterior wall of
the superior mesenteric vein (SMV). The boundary between
the drainage area of the PSPDV and the PIPDV is the major
papilla. IMV, inferior mesenteric vein; LGV, left gastric vein;
replaced RHA, replaced right hepatic artery; SpV, splenic vein.
Figure 21.4 Distal pancreatectomy with en bloc celiac axis
resection (DP-CAR). (a) The roots of the superior mesenteric
artery (SMA, white arrowhead) and the celiac axis (white arrow)
are secured at the beginning of surgery. (b) After completion of
DP-CAR, the stump of the celiac axis (white arrow) is exposed
on the dissecting plane, while the SMA (white arrowhead)is
preserved.
21.2.2.1 PV
The noteworthy branches of the PV are the posterior–
superior pancreaticoduodenal vein (PSPDV), left gastric
vein, and right gastric vein. In a cadaveric study by
Mourad et al., the authors report that the PSPDV was
absent in only one of the 45 specimens studied [13]. The
PSPDV is the most dominant branch off the PV and is
usually located on the right posterior aspect of the PV at
the superior edge of the pancreas. The PSPDV drains the
posterior–superior area of the pancreas and the duodenum. The PSPDV and PIPDV may in some cases form the
posterior arcade at the back of the pancreatic head,
although the communication between the two veins close
to the major papilla is sometimes not well developed
(Figure 21.5) [14,15]. There is some disagreement
whether the ASPDV and AIPDV form the anterior arcade
on the ventral side of the pancreatic head [14,16]. The left
gastric vein (LGV), i.e. coronary vein, branches from the
junction between the PV and SpV (type I, 58.9%), the PV
(type II, 24.4%), and the SpV (type III, 16.7%) [12]
(Figure 21.6). The right gastric vein originates in the
lower portion of the lesser curvature of the stomach [12].
This vein sometimes has a common trunk with tributaries
from the superior edge of the pancreas, which must be
controlled carefully when performing the retropancreatic
“tunneling” during a PD [17].
21.2.2.2 SpV
The noteworthy tributaries of the SpV are the LGV and
inferior mesenteric vein (IMV). As described in the
292 Chapter 21
Figure 21.6 Schematic drawings of the left gastric vein in
relation to the portal vein (PV) and splenic vein (SpV). Type I
(58.9%): left gastric vein joins the junction between the PV
and the SPV. Type II (24.4%): left gastric vein joins the PV.
Type III (16.7%): left gastric vein joins the SpV.
previous section, the LGV drains into the portal venous
confluence or the superior aspect of the SpV in 76% of
patients (see Figure 21.6). The IMV drains into the portal
venous confluence or the inferior aspect of the SpV in
72% of patients (Figure 21.7).
Figure 21.7 Schematic drawings of the inferior mesenteric vein
(IMV) in relation to the portal vein (PV) and splenic vein
(SpV). Type I (38.0%): the IMV joins the junction of the SpV.
Type II (32.7%): the IMV joins the junction between the PV
and SpV. Type III (29.3%): the IMV joins the PV.
21.2.2.3 SMV
The major tributaries of the SMV are the right gastroepiploic trunk (Henle’s trunk), the IMV, and the middle
colic vein. Zhang et al. studied 50 cases with special
reference to the branching of Henle’s trunk [18]. They
found that Henle’s trunk has 2–4 of the following veins:
the right gastroepiploic (100%), the superior right colic
(59.3%), the superior pancreaticoduodenal (85.2%), the
anterior–inferior pancreaticoduodenal (16.7%), and
other colic veins (middle right, transverse).
The main trunk of the SMV arises from the confluence
of the two first-order branches of the SMV: the jejunal
and ileal branches. The jejunal branch runs behind the
SMA in 80% of cases [19]. Katz et al. described that in PD,
one of the jejunal or ileal veins can be sacrificed without
the need for venous reconstruction, if at least one of these
venous branches is preserved [19]. In addition, they
propose that the preservation of the ileal vein is preferred
over the jejunal vein. Falconer et al. demonstrated that
when the jejunal branch crosses anterior to the SMA, the
SMA appears between the two equally thick veins [15].
Sacrificing the left limb of the SMV, usually the jejunal
vein, can be considered according to the size of the
remaining venous limb.
21.2.3 Peripancreatic nerve plexus
The peripancreatic nerves impact both the sympathetic
and parasympathetic autonomic nervous systems. The
major ganglia are the celiac and superior mesenteric
ganglia with their branches to the greater or lesser
splanchnic nerves and vagus nerves.
The innervations of the pancreatic head can be classified into two parts: (i) plexus pancreaticus capitalis 1 and
2 [20], which accounts for the nerve plexus of the SMA
and celiac axis, and (ii) plexus splenicus innervating the
pancreatic body and tail. The neural plexi around the
SMA are most likely to be involved when cancer includes
perineural invasion, thus dissection of these plexi has
been advocated in the treatment of invasive pancreatic
cancer [21,22]. It has been reported that lymphatic vessels
are present along the SMA within the SMA plexus [23],
which supports systematic dissection of the nerve plexus
along the SMA in patients with pancreatic cancer close to
the SMA.
21.2.3.1 Nerve plexus of the SMA
The SMA is surrounded by a thick nerve plexus, and the
IPDA and jejunal arteries run inside and outside the nerve
Pancreatic anatomy in the era of extensive and less invasive surgery 293
Figure 21.8 View of the pancreatic head and body in a fixed
specimen. The superior mesenteric artery (SMA) is covered by
the thick nerve plexus (yellow arrowhead), but the superior
mesenteric vein is not.
plexus (Figure 21.8). Pancreatic cancer often involves the
nerve plexus of the SMA around the IPDA (Figure 21.9).
The branches of the IPDA or jejunal artery often run
within the right half of the nerve plexus of the SMA.
Therefore, dissection of the right half of the plexus
involves ligation or sealing of these thin arterial branches.
In the left half of the plexus, no major arterial branch runs
through the plexus itself, with the exception of the
arterial branch to the body of the pancreas, which runs
along the inferior border of the pancreas.
Figure 21.10 View after pancreaticoduodenectomy for invasive
pancreatic cancer. After pancreaticoduodenectomy for invasive
pancreatic cancer, the right half of the nerve plexus of the
superior mesenteric artery (SMA, white arrowhead) is removed,
exposing the aorta (aorta, white asterisk) and the left renal vein.
The wall of the portal vein is reconstructed using a patch graft
from bilateral ovarian veins (yellow arrowhead).
During PD for pancreatic invasive cancer, the right half
of the SMA nerve plexus should be dissected for a complete radical resection (Figure 21.10). During a DP for
pancreatic cancer involving the left-side nerve plexus of
SMA, the nerve plexus should be removed for a radical
resection (Figure 21.11). Extensive resection of the nerve
Figure 21.9 Pancreatic cancer involving the nerve plexus of the
superior mesenteric artery (SMA). The pancreatic cancer
involves the gastroduodenal artery (white arrowhead) and the
distal portion of the stomach, and invades the nerve plexus of
the SMA (red arrowhead) via the inferior pancreaticoduodenal
artery (IPDA, red arrow).
Figure 21.11 View after distal pancreatectomy for invasive
pancreatic cancer. After distal pancreatectomy for invasive
cancer, the left half of the nerve plexus of the superior
mesenteric artery (SMA, white arrowhead, pancreatic head,
white arrow, ligated gastroduodenal artery, red arrow).
294 Chapter 21
plexus around the SMA can induce severe diarrhea and
disturbance of digestion and absorption, which should be
avoided to maintain optimal quality of life of patients
undergoing PD for invasive cancer.
21.2.3.2 Nerve plexus of CeA and CHA
In patients with pancreatic body cancer with invasion into
the nerve plexus around the CeA and the left side of the
nerve plexus of the SMA, these nerve plexi need to be
removed as part of a radical resection. The CeA, CHA, and
the left half of the SMA wall are exposed after complete
dissection of the nerve plexus (see Figure 21.11).
21.2.4 Peripancreatic nodal stations
The nodal distribution of peripancreatic regions has been
well classified in the General Rules for the Study of Pancreatic
Cancer [24] (Figure 21.12). Although a clinical impact of
extensive nodal dissection in patients with invasive
ductal carcinoma of the pancreas has not been proven
in randomized clinical trials, at least standard nodal
dissection is necessary for accurate staging. To perform
an accurate nodal dissection with a high lymph node
yield, the surgeon requires an excellent understanding
of the relevant nodal stations. The peripancreatic lymph
node stations have been numbered based on their locations (Table 21.1). The most frequent metastatic nodal
stations in pancreatic cancer are numbers 13, 16, and
17 [25].
21.3 Pancreatic anatomy for organpreserving peripancreatic
resection
Laparoscopic surgery, compared with open resection, has
the potential to reduce morbidity. Pancreas head resection that preserves a significant amount of pancreas tissue
has been reported, and Beger has proposed such procedures for pancreatitis [26]. These include duodenumpreserving pancreas head resection (DPPHR), inferior
Figure 21.12 Mapping of the peripancreatic and para-aortic lymph nodes. (a) Peripancreatic nodes between no. 9 and no. 18. (b)
Lymph nodes at the hepatoduodenal ligaments. (c) Lymph nodes along the superior mesenteric artery. (d) Para-aortic lymph nodes.
Source: Nakao [24]. Reproduced with permission of Lippencott, Williams, & Wilkins.
Pancreatic anatomy in the era of extensive and less invasive surgery 295
Table 21.1
Numbers of peripancreatic lymph node stations.
Lymph node
station number
1 Right cardia
2 Left cardia
3 Lesser curvature of the stomach
4 Greater curvature of the stomach
5 Suprapyloric
6 Infrapyloric
7 Left gastric artery
8a Common hepatic artery, anterior–superior
8p Common hepatic artery, posterior
9 Celiac trunk
10 Splenic hilum
11p Splenic artery, proximal
11d Splenic artery, distal
12a Hepatic artery
12b Bile duct
12p Portal vein
13a Pancreatic head, posterior–superior
13b Pancreatic head, posterior–inferior
14p Superior mesenteric artery, proximal
14d Superior mesenteric artery, distal
15 Middle colic artery
16a1 Para-aortic, superior to celiac artery
16a2 Para-aortic, between celiac artery and
16b1 Para-aortic, between left renal vein and
16b2 Para-aortic, inferior to inferior mesenteric
17a Pancreatic head, superior–anterior
17b Pancreatic head, inferior–anterior
18 Pancreatic body and tail, inferior
Anatomical location
superior mesenteric artery
inferior mesenteric artery
artery
pancreatic head resection, ventral pancreatectomy, and
so on. In addition, a variety of pancreas-sparing duodenectomy (PSD) with and without reconstruction of the
major papilla has been reported.
21.3.1 Anatomical segmentectomy of the
pancreatic head (see Video 26)
To understand the pancreatic and peripancreatic anatomy for organ-preserving surgery, it is important to
consider the embryonic origin of the pancreatic dorsal
and ventral buds. The fetal pancreas is composed of the
ventral and dorsal anlage derived from the midgut, and
the two buds fuse at week 7 or 8 of gestation, forming the
Figure 21.13 The embryological anatomy of the pancreatic
head. The pancreatic head can be divided into two parts: the
anterior segment (embryologically dorsal primordia) and the
posterior segment (embryologically ventral primordia). The
duct of Wirsung (yellow arrowhead) penetrates the two buds
and joins the duct of Santorini, making the main pancreatic
duct. The anterior–inferior pancreaticoduodenal artery
(red arrowhead) and vein (blue arrowhead) can be recognized.
The common bile duct and the duct of Wirsung are included
in the posterior segment.
pancreas. The bile duct and the duct of Wirsung originate
from the ventral bud, while the duct of Santorini arises
from the dorsal bud. The two buds fuse, rotating 270°
from their initial position, so that the ventral bud is
located behind the dorsal bud in the adult pancreas.
On fixed casts of the pancreatic head obtained from
cadavers, anatomical segmentectomy of the pancreatic
head along the embryological fusion plane is feasible,
preserving the embryological ventral primordium containing the common bile duct (Figure 21.13) [27]. It is
therefore theoretically feasible to perform anatomical
anterior segmentectomy of the pancreatic head for intraductal papillary mucinous neoplasm (IPMN) in the
embryological dorsal pancreas, dividing the fusion plane
between the dorsal and ventral primordia [28]. However,
a significant pancreatic fistula from the wide dissection
plane and reconstruction of the main pancreatic duct
carry a high risk of significant morbidity [29]. In addition,
anatomical resection of the embryological ventral bud
involves resection of the lower bile duct. Subsequently,
reconstruction of the main pancreatic duct, as well as the
bile duct, is required (Figure 21.14). The benefit of preserving the anterior bud of the patients tends to be very
limited and therefore in most cases, PD is preferable for
patients with neoplasm limited to the ventral bud.
296 Chapter 21
21.3.2 Pancreas-sparing duodenectomy
In patients wi th duodenal gastrointestinal stromal
tumor (GIST) or famil ial adenomatous polyposis of
the duodenum, resection of the duodenum while preserving the pancreas m ay be an indication for PSD.
During PSD, the major/minor papilla, branches from
the anterior–inferior pancreatico duodenal arteries and
veins, and the p osterior– superior and –inferior pancreaticoduodenal arteri es and veins are divided. PSD
might be indicated in patients with duodenal GIST,
which has a negligible ris k of nodal metastasis or direct
Figure 21.14 Resection of the embryologically ventral
primordium. After resection of the embryologically ventral
primordium, the lower bile duct, which is originally buried in
the ventral primordium, was exposed on the dissecting plane.
The plane coincides with the embryological fusion between the
ventral and dorsal buds.
KEY POINTS
• The arterial tributaries to the pancreas originate from either the celiac artery or the superior mesenteric artery. There are
several variations of the communication between the inferior pancreaticoduodenal artery and the first jejunal artery. It is
essential to safely control these arteries early during PD in o rd er to minimize blood flow to the pancreatic head during the
resection.
• There are several variations of the communication between the splenic vein, inferior mesenteric vein, the superior mesenteric
vein, and the portal vein. The posterior pancreaticoduodenal veins provide drainage of the posterior pancreatic head to the portal
system.
• In the treatment of invasive pancreatic cancer, partial resection of nerve plexus of the celiac artery and the superior mesenteric
artery, and a peripancreatic lymph node dissection is required for oncological reasons.
• The pancreatic head can be divided into two parts along the embryological primordia: the dorsal bud and the ventral bud.
Anatomical segmentectomy is theoretically possible, but practically it may be too complicated.
• Pancreas-sparing duodenectomy or duodenum-preserving pancreatic head resection requires excellent knowledge of the
peripancreatic anatomy.
invasion to adjacent organs [ 30], or in very select
patients with preinvasive or very early duodenal cancer [31]. The long-term prognosis of PSD for GIST is
reported to be satisfactory [32].
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Videos 20–26 will be of interest to readers of this chapter.
Visit the companion website at:
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CHAPTER 22
Management of solid and cystic lesions
of the pancreas
David Fogelman and Robert A. Wolff
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA
EDITOR COMMENT
This comprehensive chapter on pancreatic tumors discusses multidisciplinary management of pancreatic adenocarcinoma, pancreatic
neuroendocrine tumors, and pancreatic cystic neoplasms as well as less often encountered pathologies such as metastases to the
pancreas and lymphoepithelial cysts. While pancreatic resection in general has become safer, the advent of advanced laparoscopic
pancreatectomy might contribute to reducing operative morbidity further. Pancreatic cancer therapy today requires a multidisciplinary
approach, and this chapter by expert pancreas medical oncologists allows surgeons to put pancreas cancer surgery into the context of
chemotherapy and/or radiation therapy.
With the widespread use of axial abdominal imaging, there has been a significant increase in the detection of pancreatic cystic lesions.
The minimally invasive pancreatic surgeon will frequently be asked to manage these patients because removal of potentially
premalignant or early-malignant cystic lesions with prophylactic intent makes these operations well suited for the lesser morbidities
associated with a minimally invasive approach. Therefore, it is critical that the surgeon becomes very familiar with the work-up,
indications for resection, and surgical approaches to managing these cystic lesions.
Keywords: borderline resectable pancreatic cancer, cystic tumor of the pancreas, diagnosis of cystic lesions of the pancreas, intraductal
papillary mucinous neoplasm, lymphoepithelial cyst, metastases to the pancreas, mucinous cystic neoplasm, neoadjuvant therapy for
pancreatic cancer, pancreatic adenocarcinoma, pancreatic neuroendocrine tumor, serous cystic neoplasm, solid pseudopapillary tumors
of the pancreas, solid tumor of the pancreas
22.1 Introduction
Pancreatic adenocarcinoma is by far the most common
malignancy in patients discovered to have a solid lesion in
the pancreas, and in the United States, the incidence of
pancreatic adenocarcinoma has increased from approximately 32 000 cases per year a decade ago to over 46 000
currently [1,2]. Similarly, pancreatic neuroendocrine carcinomas, the second most common malignant histology,
also appear to be rising in incidence [3]. Furthermore,
with the widespread use of cross-sectional imaging (computed tomography [CT] and magnetic resonance [MR]), a
growing number of people are being found to have cystic
lesions within the pancreas, many of which represent
Laparoscopic Liver, Pancreas, and Biliary Surgery: Textbook and Illustrated Video Atlas, First Edition.
Edited by Claudius Conrad and Brice Gayet.
© 2017 John Wiley & Sons, Ltd. Published 2017 by John Wiley & Sons, Ltd.
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intraductal papillary mucinous neoplasms (IPMNs) of the
pancreas.
This chapter will focus on the diagnostic work-up,
staging, and subsequent management of patients with
solid and cystic pancreatic lesions.
22.2 Solid tumors of the pancreas
In general, curative treatment of solid neoplasms of the
pancreas requires complete resection of the tumor
mass, and in the case of pancreatic adenocarcinoma,
the delivery of adjuvant therapy has a modest impact
on overall survival for p atients undergoing curative
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