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Modified ALPPS Procedure

NobuyukiTakemura, KyoujiIto, andNorihiroKokudo
36
Abstract
In patients with hepatobiliary malignancies located around the hepatic hilum or those with multiple meta­static lesions, a major hepatectomy is the only curative treatment. A major hepatectomy functions to remove tumor cells concomitant with the hemi-liver or liver parenchyma; however, there is a risk of insufcient rem­nant liver volume, which might cause postoperative mor­bidity and mortality in these extended hepatectomies. To overcome this problem, Makuuchi etal. rst introduced preoperative portal vein embolization (PVE), which increases the volume of the future liver remnant (FLR), allowing extended hepatectomy to be performed safely. However, there is a maximum volume increase in PVE of approximately 40%. The associating liver partition and portal vein ligation for the staged hepatectomy (ALPPS) procedure was rst introduced in 2012, and was shown to increase the FLR by up to 80%. Initially, the major prob­lem of the ALPPS procedure was a high morbidity and relatively high mortality compared to these of PVE.To overcome this problem, various modications of the ALPPS procedure have been proposed, and satisfactory results have been reported. In this section, various modi­ed ALPPS procedures and their results are presented.

36.1 Introduction

A major hepatectomy is the only curative treatment for patients with extensive hepatobiliary malignancies located around the hepatic hilum or with multiple bi-lobular meta­static lesions. A major hepatectomy provides a chance of cure by removing tumor cells concomitant with the hemi-
N. Takemura (*) · K. Ito · N. Kokudo Department of Surgery, Hepato-Biliary Pancreatic Surgery Division, National Center for Global Health and Medicine, Tokyo, Japan e-mail: ntakemura@hosp.ncgm.go.jp
liver or liver parenchyma. However, there is a risk of insuf­cient remnant liver volume, which may lead to postoperative live failure in these cases with extended hepatectomy. To overcome this problem, Makuuchi etal. rst introduced pre­operative portal vein embolization (PVE), which increases the volume of the future liver remnant (FLR), allowing extended hepatectomy to be performed safely [1]. However, PVE has a maximum volume increase of approximately 40% [2].
Schnitzbauer etal. introduced combined portal vein liga­tion and in situ liver partition-induced rapid liver hypertro­phy of the liver remnant [3], which was later named associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) [4]. The ALPPS procedure enables a rapid FLR increase of up to 80%; despite this improvement, initial studies reported very high morbidity and mortality [3,
5] in compensation for very rapid hepatic hypertrophy. The
majority of the mortality associated with the ALPPS proce­dures occurred due to bile leakage and septic complications. It is also important to consider the interval to the second operation, with early reports suggesting that the second sur­gery should be performed within 7 to 9days after the rst operation [3, 5]. In the ALPPS procedure, even with rapid and sufcient liver hypertrophy from the aspect of liver vol­ume only, the presence of immature hepatocytes in the FLR may be one of the reasons for postoperative liver failure after the second operation [6]. Furthermore, Olthof et al. stated that the liver volume overestimates liver function measured by hepatobiliary scintigraphy [7].
Although there are still some problems that need to be overcome, the ALPPS procedure is a novel technique for use in patients with extensive, initially unresectable tumors and very small FLR volumes, especially as a salvage procedure in patients with portal vein embolization/occlusion failure [8]. Various modications have been proposed to overcome the problems associated with ALPPS procedures. In this sec­tion, we introduce the modications that have led to safer ALPPS procedures and discuss their advantages and disad-
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 M. Makuuchi et al. (eds.), The IASGO Textbook of Multi-Disciplinary Management of Hepato-Pancreato-Biliary Diseases,
https://doi.org/10.1007/978-981-19-0063-1_36
285
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N. Takemura et al.
vantages with respect to inducing remnant liver hypertrophy in patients with advanced hepatobiliary malignancies with an insufcient FLR.

36.2 Discussion

The ALPPS procedure has been introduced as a new treat­ment strategy for patients with extensive hepatobiliary malignancies with a small FLR volume [3, 4]. Originally, the ALPPS procedure involved the complete mobilization of the right hemi-liver and total parenchymal transection from the falciform ligament to the inferior vena cava, in addition to the resection of the Glissonian sheath branches of segment 4 and hepatoduodenal ligament dissection for the ligation of the right portal vein (Fig.36.1). Given the rapid hypertrophy of the FLR, the second stage of the hepatectomy was per­formed 7 or 9days after the rst hepatectomy [3, 5]. Initial reports on ALPPS procedures demonstrated high morbidity and mortality rates in 12% to 15% of patients, the majority of which were due to biliary and infectious complications and liver failure [3, 5]. Several modications have been made to reduce these adverse effects, and improved results have been reported.
4. More recent experimental and clinical data has shown that rapid liver hypertrophy is induced by partial transection of at least 50% [911]. Furthermore, conducting partial liver tran­section results in signicantly lower morbidity and mortality [9, 10].

36.2.2 Hepatoduodenal Ligament Dissection

Cholecystectomy and the dissection of the hepatoduodenal ligament are essential to correctly approach the right portal vein for ligation; however, this tends to cause dense adhesion around the hepatic hilum and increases the difculty of the second stage hepatectomy [10]. Another problem with hepa­toduodenal ligament dissection is the risk of tumor exposure when the tumor is located close to the hepatic hilum. In order to avoid the skeltonization of the hepatoduodenal ligament, the transhepatic approach or the approach via the mesenteric vein have been proposed for intrahepatic portal vein occlu­sion [1215]. If it is difcult to puncture the portal vein because of the presence of multiple bi-lobular tumors, the occlusion approach to the intrahepatic portal vein can be shifted from the transhepatic to the inferior mescenteric or ileocecal portal vein instead.

36.2.1 Parenchymal Transection

Total parenchymal transection from the falciform ligament to the inferior vena cava was performed in the original ALPPS procedure; this had the potential to result in biliary complications of the biliary branches of segment 4, as well as infectious complications of the ischemic area of segment
Fig. 36.1 Conventional ALPPS procedure with total parenchymal
transection to the inferior vena cava, with resection of the Glissonian branches of segment 4, full mobilization of the right hemiliver, and hepatoduodenal ligament dissection
36.2.3 Interval Between theFirst andSecond
Stage Hepatectomy
The main feature of the ALPPS procedure is the rapid hyper­trophy of the FLR, which makes it possible to perform a sec­ond hepatectomy, even with a short interval. Initial reports advocated that the rapid hypertrophy of the procedure enabled a second hepatectomy within an interval of 7 to 9 days after the rst operation [3, 5]. However, there are debates on whether liver hypertrophy truly reects sufcient functional recovery of the liver. Indeed, microscopic exami­nation and hepatobiliary scintigraphy of the FLR after the ALPPS procedure have highlighted the risk of hepatocyte immaturity and insufcient liver functional recovery [6, 7]; thus, delayed second surgery of the ALPPS procedure is cur­rently recommended [7, 16].
These modications are shown in Fig.36.2.
36.2.4 Various Modied Subtypes
oftheALPPS Procedure
36.2.4.1 Partial ALPPS
Petrowsky etal. rst introduced partial transection (50% to 80% transection of the complete transection plane) in the rst stage of the operation. This modication was based on their experimental models and the hypothesis that partial
36 Modied ALPPS Procedure
Fig. 36.2 Modied ALPPS procedure with half parenchymal transec-
tion without resection of the Glissonian branches of segment 4, without mobilization of the right hemiliver, and without hepatoduodenal liga­ment dissection. Portal vein occlusion is done transhepatic approach or trans superior/inferior mesenteric vein approach
parenchymal transection triggers a comparable degree of the regeneration of the FLR to complete transection and reduces postoperative complications [9]. This modication, named Partial ALPPS, achieved reduced morbidity and mortality and is currently the standard modication of the ALPPS procedure.
36.2.4.2 Hybrid ALPPS
Li etal. suggested an alternative ALPPS method that con­sisted of three steps: parenchymal splitting, right PVE, and two-stage hepatectomy, named hybrid ALPPS [12]. This method can avoid adhesion around the hepatic hilum, and can be applied even when the tumor is located close to the hepatic hilum. However, this approach is difcult in cases with multiple bi-lobular tumors as it is difcult to ensure an adequate transhepatic puncture line from the body surface.
36.2.4.3 Mini-ALPPS/ALPTIPS
De Santibanes etal. proposed a modication of the ALPPS procedure, known as the “Mini-ALPPS” technique, in which partial parenchymal transection combined with intraopera­tive PVE is performed via the inferior mesenteric vein with minimum liver mobilization [13]. A similar modication was reported by Sakamoto etal., who used the ileocecal vein approach for PVE as an alternative to the inferior mesenteric vein [14, 15]. Both modications can avoid dense adhesion around the hepatic hilum during the second stage hepatec­tomy. Furthermore, these procedures can be performed when the tumors are located close to the hepatic hilum without tumor exposure and in cases with multiple bi-lobular tumors where transhepatic puncture of the portal vein may be difcult.
287
36.2.4.4 Segment 4 Portal Pedicle-spared
ALPPS
In ve patients, Tanaka etal. reported a modication of the ALPPS procedure that avoids the division of the portal pedi­cle and prevents parenchymal necrosis due to ischemia. Portal vein ligation was performed using this method; how­ever, the ligation of the Glissonian sheath branches of the additional hepatic area in the future liver removed are pre­served [17]. Since the term “modied ALPPS” is misleading in this chapter, we have changed it to “Segment 4 portal pedicle-spared ALPPS,” derived from their procedures. Of course their modication of the preserved portal pedicle were not only segment 4 branch, however, considering the original ALPPS procedure which completely divide portal pedicle of segment 4, this nomenclature seems to be a good reection of their modication. This modication achieved rapid liver hypertrophies, which were almost identical to those of the original ALPPS procedure without the associ­ated mortality.
36.2.4.5 Tourniquet ALPPS
Robles etal. reported using a tourniquet as an alternative to parenchymal splitting [18]. In this procedure, a tourniquet was placed around the parenchymal transection line using the hanging maneuver, and the right portal vein was ligated and cut. Although this modication is easy to perform during the rst stage of the operation, during the second stage, severe adhesion occurs around the hepatic hilum, which requires a longer operation time because parenchymal tran­section was not performed during the rst stage. Furthermore, two mortalities were reported in their initial report, even with the modication.

36.3 Conclusion

The ALPPS procedure provides a potential cure for patients with extensive and initially unresectable hepatobiliary malig­nancies with a small FLR.Various modications have been proposed to overcome the high morbidity and mortality asso­ciated with the ALPPS procedure; these include reduced hepatic parenchymal transection, no bile duct resection, no dissection of the hepatoduodenal ligament, laparoscopic approach, and avoiding the mobilization of the right hemi­liver. However, the safest approach to increase the FLR is PVE, and the indication of the ALPPS procedure should be limited to patients with a very small FLR or failure of PVE. Even with the rapid hepatic hypertrophy associated with the ALPPS procedure, a second hepatectomy should be performed following the maturation of the hepatocytes in the FLR.The modications mentioned in this section should be selected on a case-by-case basis in order to increase the safety of the ALPPS procedure.
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References

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11. Linecker M, Kambakamba P, Reiner CS, et al. How much liver needs to be transected in ALPPS? A translational study investigat­ing the concept of less invasiveness. Surgery. 2017;161(2):453–64.
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Artery-First Approach inPancreaticoduodenectomy
DaisukeBan andMinoruTanabe
37
Abstract
Due to its anatomical characteristics, cancer of the pan­creatic head often invades the superior mesenteric vein (SMV), the portal vein (PV), and the plexus surrounding the superior mesenteric artery (SMA). Several different approaches to pancreaticoduodenectomy (PD) have been proposed in order to achieve R0 resection.

37.1 Introduction

Due to its anatomical characteristics, cancer of the pancre­atic head often invades the superior mesenteric vein (SMV), the portal vein (PV), and the plexus surrounding the superior mesenteric artery (SMA). Several different approaches to pancreaticoduodenectomy (PD) have been proposed in order to achieve R0 resection.
The mesenteric approach established by Nakao [1] in the 1990s is based on the concept of isolated pancreatectomy, in which the SMA and SMV are rst dissected without kocher­ization. The concept of the artery-rst approach to divide the SMA from the pancreatic head by approaching the SMA at an early stage of the PD procedure seems to have origi­nated in the mesenteric approach of Nakao et al. Later, Pessaux et al. reported a comprehensive variety of approaches for the treatment of pancreatic head cancer with suspected SMA invasion [2]. The term “artery-rst approach” proposed by Weitz etal. has now become widely used internationally [3].
37.2 Artery-First Approaches inPD
Unlike in artery-rst PD, the standard PD procedure is to dissect the gastroduodenal artery, perform a bile duct dissec­tion, perform pancreatic dissection, ligate and dissect the small vessels owing from the pancreatic head to the SMV, and nally dissect the space between the pancreatic head and the SMA.In contrast, artery-rst PD is a procedure to sepa­rate the pancreatic head from the SMA by ligating and dis­secting the blood vessels feeding the it from the SMA, mainly the rst jejunal artery (FJA) and inferior pancreato­duodenal artery (IPDA) at the root, at an early stage of sur­gery. The advantages of an artery-rst approach are that resectability can be determined at an early stage of the pro­cedure and the amount of blood loss during surgery can be reduced because the feeding vessels are blocked [411]. The relative anatomical position of the pancreatic head to unci­nate is dorsal to the origin of the SMA; bleeding from the SMA or SMV can be fatal. The approach is not always easy, as it is often accompanied by tumor invasion and inamma­tion. In order to ensure the safety and curative potential of the procedure, various approaches to the SMA from different directions have been proposed, and several names have been given to the same approach. We have modied the terminol­ogy summarized by Sanjay etal. [12] and revised it as shown in Fig.37.1.

37.3 Right-Posterior Approach

For the right-posterior approach, kocherization is performed rst. (Fig.37.2) The duodenum and the head of the pancreas
D. Ban (*) Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan e-mail: dban@ncc.go.jp
M. Tanabe Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 M. Makuuchi et al. (eds.), The IASGO Textbook of Multi-Disciplinary Management of Hepato-Pancreato-Biliary Diseases,
https://doi.org/10.1007/978-981-19-0063-1_37
are sufciently mobilized to dissect the fusion fascia of Treitz, expose the inferior vena cava (IVC) and the origin of the left renal vein, and proceed with dissection to the aorta. The pancreatic head is lifted and the brous tissue around the origin of the SMA is dissected to identify and divide the IPDA.The SMA is then separated from the uncinate. Further
289
290
Fig. 37.1 Artery-rst approaches for pancreaticoduodenectomy. RP
right-posterior approach, U right-uncinate approach, M mesenteric approach, LP left-posterior approach
D. Ban and M. Tanabe
postoperative complications [13]. Moreover, the number of lymph nodes dissected and the rate of R0 resection were the same for both procedures in both reports, and the prognosis was not affected.
In laparoscopic PD, some articles described surgical pro­cedure for approaching from the posterior side of the SMA.Wang etal. reported the usefulness of the inferior duo­denal approach [14]. This method approaches from behind the SMA.The PV/SMV was also exposed from the posterior side. Honda etal. reported a similar approach that exposed the posterior aspect of the SMA from the caudal side [15].

37.4 Right-Uncinate Approach

There are many reports on approaching from between the ventral side of the pancreatic uncinate and the SMV. (Fig.37.3) Depending on the structure to be identied rst, the name of the approach varies. Reports that focus on the pancreatic uncinate are called “uncinate-rst” and those that focus on the rst jejunal vein (FJV) that ows into the SMV adjacent to the pancreatic uncinate are called “FJV-rst”. When dissecting between the pancreatic uncinate and the SMV, it is necessary to dissect several small veins that ow into the FJV [16]. After that vein is divided, the inferior pan­creatoduodenal artery (IPDA) is dissected to separate the pancreatic uncinate from the SMA.
In 2007, Shukla etal. reported a complete approach to the SMA/SMV by dissecting the ligament of Treitz and the
Fig. 37.2 Right posterior artery for pancreaticoduodenectomy
dissection then proceeds in order to expose the PV-SMV.The advantage of this approach is that it allows for early assess­ment of resectability by determining the extent to which the tumor has invaded the SMA plexus prior to treatment of the intestinal and bile ducts. In addition, appropriate en bloc resection of the posterior side of the pancreas can be per­formed. On the other hand, it is easily affected by adhesions and inammation around the pancreatic head. It is also easily inuenced by body shape, which may make this procedure difcult in obese patients.
Dumitrascu etal. compared artery-rst PD with standard PD [9]. They reported that artery-rst PD can be completed faster and with less blood loss, and with no difference in postoperative complications. Figueras etal. conducted a sim­ilar study and also found that artery-rst PD required less time, resulted in less blood loss, again with no difference in
Fig. 37.3 Right posterior artery for pancreaticoduodenectomy. SMA
superior mesenteric artery, SMV superior mesenteric vein
37 Artery-First Approach inPancreaticoduodenectomy
proximal jejunum and passing them to the right under the superior mesenteric vessels [17]. In 2010, Hackert et al. reported an “uncinate-rst” approach to rst dissect between the pancreatic uncinate and SMA [18]. Nakamura et al. reported that the FJV can be identied rst, after which the SMA can be accessed for a safer approach. Shrikhande etal. reported advantages in terms of blood loss, reduced opera­tive time, postoperative complications, lymph node dissec­tion, and margin status.
Although not necessarily artery-rst, there are also many reports on approaching from the pancreatic uncinate when performing laparoscopic PD.Zimmitti etal. reported that the right-uncinate approach is useful as an artery-rst approach in laparoscopic PD [19, 20]. However, it is also true that the right-uncinate approach often overlaps with the right­posterior approach in some procedural elements, and it is dif­cult to clearly classify them. The Cattell-Braasch maneuver involves dissecting the right-sided white line of Toldt, dissect­ing the dorsal side of the ascending colon and the mesentery of the small intestine, and additionally performing sufcient kocherization to elevate it broadly to the left, including the pancreatic head of the duodenum. This method ensures that the root of the SMA can be approached [21, 22]. There is also the derotation technique by Sugiyama etal. to be considered. This is a method to expand the mesopancreas to the right side by generously dissecting the proximal small intestine from the duodenum, releasing the mesenteric rotation, and exten­sively pulling the mesopancreas to the right side in order to reliably approach the root of the artery branching from the SMA to the pancreatic head [23, 24]. This approach is gener­ally easier to understand anatomically because of the traction deployment of the pancreatic head, and it is easier to deter­mine the resectability between the SMA and the tumor on the ventral side of the pancreatic head.

37.5 Mesenteric Approach

In 1993, Nakao etal. proposed a mesenteric approach to pan­creatic head resection using a catheter to bypass SMV blood to the intrahepatic portal vein or systemic circulation as an iso­lated pancreatectomy. They proposed to call this the mesen­teric approach. This method identies the SMA and SMV through an incision in the fascia over the SMA on the dorsal side of the transverse mesentery without kocherization, with or without portal vein bypass; the middle colonic artery aris­ing from the SMA and the middle colonic vein owing into the SMV are dissected, and the SMA and SMV are widely separated. (Fig.37.4) Next, the SMA origin is entered from the right side of the pancreatic uncinate and SMA to widen the space between the SMA and SMV.This technique is basically synonymous with the inferior infracacolic approach proposed by Weitz et al. in 2010. This method can be used to evaluate
291
Fig. 37.4 Mesenteric approach. SMA superior mesenteric artery, SMV
superior mesenteric vein, U uncinate, T-colon transverse colon
resectability by conrming the relationship between the tumor and SMA in the head of the pancreas at an early stage of sur­gery. It is undoubtedly useful for tumors in the pancreatic uncinate area. Unfortunately, whether there is any oncological benet has not been established. Currently, a randomized con­trolled trial of this technique compared with standard PD is underway in Japan, and the results are eagerly awaited [25].

37.6 Left-Posterior Approach

Kurosaki etal. reported data on the left-posterior approach [26]. After the proximal jejunum and duodenum are dis­sected and innervated from the left side, the proximal jeju­num is towed to the left side, exposing the dorsal side of the mesentery and the left to dorsal side of the SMA. (Fig.37.5) The rst jejunal artery arising from the SMA is then dis­sected at the root. The root of the rst jejunal artery or the IPDA branching from the rst jejunal artery is also dissected. Once it is conrmed that there is no tumor invasion between the pancreatic uncinate and the SMA, the jejunum is dis­sected. The SMV is not visible in this eld of view, so we approach it again from the right. Kawabata etal. reported the oncological benet of the mesenteric approach as well as resection of the mesopancreatoduodenum [27]. This approach can be used to reach the SMA without mobilization of the duodenum or colon and may be particularly useful for tumors in the pancreatic uncinate. However, this approach is often difcult by laparoscopy and few cases have been reported [28].
292
D. Ban and M. Tanabe
Fig. 37.6 Anterior approach. SMA superior mesenteric artery, SMV
superior mesenteric vein, U right-uncinate approach, T-colon transverse colon
Fig. 37.5 Left-posterior approach. SMA superior mesenteric artery,
SMV superior mesenteric vein, U right-uncinate approach, T-colon
transverse colon

37.7 Anterior Approach

The SMA/SMV is approached anteriorly from the inferior border of the pancreas, and the SMA secured and pulled to the left side. The SMV is then secured and pulled to the right side. The method is to dissect the SMA and the pancre­atic uncinate by extracting the tissue between them. In 2010, Hirota etal. designated this procedure an inferior supracolic approach, and in the original report, the approach was to dissect the stomach at the pylorus and the pancreas at the pancreatic neck, exposing a wide PV-SMV and SMA [29]. The advantage of this method is that it allows for en bloc resection by isolating the blood vessels without touching the tumor. However, a disadvantage of the original method as reported by Hirota etal. was that gastrectomy and pancre­atic resection are not always necessary to evaluate resect­ability. In this sense, it is not clear whether the method of Hirota etal. can be called artery-rst. In the method reported by Inoue etal., SMA/SMV is approached prior to the dis­section of the digestive tract and pancreatic dissection, which is truly an artery-rst anterior approach [8]. (Fig.37.6).

37.8 Mesopancreatic Resection

Although various artery-rst techniques have been proposed, the main objective is to resect the pancreatic head from the SMA en bloc leaving no residual tumor. Similarly, the con- cept of resection of the mesopancreas overlaps with the con­cept of artery-rst. However, the denition of mesopancreas is often problematic because it is related to the extent of resection. Gockel etal. referred to the chordae, or ber bun­dles, between the blood vessels and the pancreas, as the mesopancreas [30]. It was described as “a vascular-rich con­nective tissue extending from the dorsal surface of the pan­creatic head to the SMV/SMA, histologically containing fat, sparse connective tissue, and nerve bers”. Kawabata etal. proposed the concept of mesopancreatoduodenum for the region including the mesopancreas and the duodenal mesen­tery up to the left margin of the SMA.They then reported that there was an oncological benet to be derived from sec­tioning at the root of the rst jejunal artery to resect the mesopancreatoduodenum [27]. Wu etal. suggested dividing the mesopancreas into an anterior part up to the dorsal portal vein and a posterior part between it and the SMA [31]. In contrast, Sharma and Isaji pointed out that the term “meso-” evokes the mesentery (mesorectum, mesocolon, etc.) but is not an appropriate term because it does not meet the deni­tion of mesentery and is better referred to as pseudomeso-
37 Artery-First Approach inPancreaticoduodenectomy
293
pancreas [32]. However, it is also convincing that it is hard to abandon the idea that this ber bundle is a membrane­enclosed structure. If viewed dorsally, this is because the celiac plexus and this ber bundle are separated by Treitz’s posterior pancreatic fascia [33]. Muro et al. [34], through anatomical analysis of the pancreatic plexus region, revealed that the bers are quite intricately intertwined and can be divided into ventral and dorsal portions with different runs. This led to the proposal to call the layered chord-like struc­tures, together with small blood vessels and lymphatic ves­sels, the P-A ligament that connects the aorta and its main branches to the pancreas. In the area surrounding the pan­creas, there are many variations in the trajectories of the arteries, and therefore, the paths of the nerves are also very complicated.
As mentioned above, the extent of resection of the meso­pancreas is quite variable among institutions. The artery-rst approach is a concept for which it is easier to arrive at a com­mon understanding in respect of the terminology. On the other hand, it should be noted that the details of the extent of resection are fraught with problems such as the issue of the mesopancreas. From this point of view, the Level I, II, and III classication proposed by Inoue etal. is a very realistic strat­ication that is one step ahead of artery-rst [35].
37.9 The Outcome ofArtery-First
Approaches
Unfortunately, there still appear to be no high-quality reports on the short- and long-term surgical outcomes of artery-rst approaches relative to standard PD. Several retrospective comparative studies have reported a reduction in operative time, intraoperative blood loss, and need for blood transfu­sion [9, 35]. There are reports of improved R0 resection rates, increased number of resected lymph nodes [27], and improved prognosis [26]. However, many others have not been able to show any oncological benet. There have been several meta-analyses comparing artery-rst PD with stan­dard PD.According to some meta-analyses [3638], intraop­erative blood loss and the proportion of patients requiring intraoperative transfusions was signicantly lower in the artery-rst group. Clearly increased R0 resection rates and overall survival have been reported for artery-rst PD.However, there were no differences in mortality, and no differences in tumor pathological factors.
The artery-rst approach is considered to improve R0 resection with respect to SMA margins by reliably dissecting the SMA nerve plexus in close proximity to the pancreatic head during dissection from the SMA. The principle that completes margin-negative resection leads to improved sur-
vival has facilitated the artery-rst approach. It is also hypothesized that the artery-rst approach reduces intraop­erative circulating tumor cells (CTCs), which may contribute to improved survival. This is based on the theory that the GDA and IPDA are dissected prior to kocherization, and the veins are also dissected to prevent the outow of CTCs. A recent report showed that CTCs in the portal vein were sig­nicantly reduced in 12 patients who underwent artery-rst PD, and that the MST of standard PD was 13.0 months, while that of artery-rst PD was improved to 16.7months [39]. Because of the small size of this cohort, we have to be careful in the interpretation of these results. In fact, accord­ing to a report by Yamamoto et al., among the reports of artery-rst approaches, kocherization is often preceded by arterial dissection, and the order of intestinal dissection and pancreatic dissection varies [40].
There are many reports that the surgical advantage of the artery-rst approach is that early dissection of the IPDA prior to dissection of the veins in the outow tract prevents congestion in the pancreatic head and reduces intraoperative bleeding. Intraoperative bleeding is a risk factor for postop­erative complications, which may have led to a reduction in postoperative complications in artery-rst PD.
Here, it should be mentioned that there are some limita­tions to the reports so far, all of which are on non- randomized and retrospective studies. One of the advantages of the artery-rst approach is that resectability is determined early in the surgery, which may result in a relative increase in sur­vival due to the exclusion of advanced cases and hence act as a selection bias. It is unfortunate that there are few reports on negative laparotomy; and there seem to be no reports at all describing the rate of failure to undergo PD after an artery­rst approach. On the other hand, it is also possible that these reports show biased results reecting the enhanced ability of the experts in high-volume centers to implement the artery­rst approach. Even though the artery-rst approach is not a new technique, it is difcult to collate high-quality evidence. This is due to the heterogeneity in patient backgrounds and the technical demands made on the surgeons who perform the procedures. However, an RCT of the mesenteric versus standard approach is currently underway in Japan, and the results are eagerly awaited [25].

37.10 Summary

In performing PD for pancreatic head cancer, especially for advanced pancreatic head cancer, it is essential to consider (1) curative resection, (2) appropriate evaluation of resect­ability, and (3) safe resection. Therefore, the approach to the SMA, which is the most critical stage of the procedure, is the
294
D. Ban and M. Tanabe
key. How to evaluate the status of SMA and tumor in the pancreatic head at the early stage of surgery and how to surely and safely proceed are important issues for the perfor­mance of safe and curative surgery. Various approaches that have been proposed have been described in the literature, all of which have their strengths and weaknesses depending on the individual condition of the tumor in the pancreatic head cancer patient. These variables include the size of the tumor, whether it is ventral or dorsal to the pancreatic head, and whether it is in the pancreatic uncinate. I believe that most experts do not stick to a single approach, but rather combine and use several approaches depending on the situation with the individual patient. I would like to encourage surgeons who are learning PD to benet from the approaches that experts have developed so far, and to become familiar with multiple approaches to ensure a reliable artery-rst approach.
Conict of Interest Statement There are no conicts of interests for any of the authors.

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