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Pancreatic Cancer and Arterial Resection
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Aggressive arterial resection (AR) in surgical treatment for locally advanced pancreatic cancer (LAPC) has gradually been encouraged thanks to new chemotherapy regimens such as FOLFIRINOX or Gemcitabine and nab-paclitaxel, which have provided more adequate patient selection and local tumor suppression justifying aggressive local resection. The development of surgical techniques provides the safety of AR for even major visceral arteries such as the celiac axis or superior mesenteric artery. 

pancreatic cancer

1. Indroduction

Pancreatic cancer (PC) is a dismal clinical entity[1]. For localized PCs, resection is the only chance for cure. Theoretically, R0 resection is one essential philosophy for cancer treatment even if the local tumor has invaded major visceral arteries. However, aggressive biology of PC accompanied with occult metastasis has precluded simply extending the resection. Pancreatectomy is accompanied by high morbidity, and extended resection including arterial resection (AR) or multi-organ resection has been a challenge because of substantial mortality [2][3].

2. Management for the Involvement of the Superior Mesenteric Artery

In advanced pancreatic uncinate cancers, the superior mesenteric artery (SMA) is the most common artery that is invaded and becomes a reason for unresectable or pathologically noncurative resection [3][4][5]. Until recent years, a large series of SMA resections for PCs was quite limited, and mortality after SMA resection had reportedly been higher than ordinal pancreatectomies, which discouraged the aggressive resection of LAPCs involving the SMA [6][7][8][9] (Table 1). As an alternative, periadventitial dissection (PAD) of the SMA had been proposed to pursue the local control of the peri-SMA region. Inoue et al. presented a standardized technique of SMA-PAD using the supracolic anterior artery-first approach, which resulted in no mortality over 158 patients, with a R0 rate of 74% [5][10]. Extended resection of the peri-SMA nerve plexus was assumed to cause neurogenic diarrhea, which would lead to insufficient patient recovery or adjuvant therapy. Inoue et al. documented that the incremental administration of an opium tincture according to the frequency of watery diarrhea was effective and easy to adjust to, with satisfactory diarrhea control, leading to sufficient adjuvant therapy introduction (83%) [5]. For more advanced tumors that cause encasement of the artery, SMA resection would be required. Recently, some high-volume centers with outstanding expertise in pancreatic resections have reported large series of arterial resections for PCs, including more than 30 cases of SMA resections [11][12]. Bachellier et al. [11] reported a large single-center series, including 34 SMA resections. They achieved the lowest mortality ever (5.1% of all patients with AR), which represented the improved safety of SMA resection and reconstruction. They mainly employed an end-to-end anastomosis using autografts such as a great saphenous vein and noted that reconstruction with an artificial graft caused thrombosis, leading to in-hospital mortality. Loos et al. [12] reported another large series involving 30 SMA resections with an acceptable mortality of 6.7%. They also performed a learning curve analysis and concluded that even an experienced pancreatic surgeon needed more than 12 cases of AR to minimize the mortality. An optimal reconstruction technique has never been established and likely depends on the length of a resected segment. Previous reports on SMA reconstruction employed end-to-end anastomosis or anastomosis to the aorta with or without graft interposition (Figure 1A,B,D,E) and a rotation of the splenic artery (SpA) (Figure 1C) [13][6][9][11][12][14][15][16][17][18][19][20][21][22][23][24]. Westermark et al. [25] proposed a safe technique of end-to-end anastomosis of the SMA. They recommended the Cattel-Braasch maneuver, wherein the total mesentery is detached from the retroperitoneum to facilitate a tension-free anastomosis. Sterile ice in a surgical towel was placed in the lower sub-mesocolic abdomen to reduce the warm ischemia of the small intestine. The Cattel-Braasch maneuver enabled tension-free anastomosis even after SMA resection of 4 cm in length. Accordingly, SMA resection is now no more an anecdotal tool but one possible option for LA pancreatic head cancers. Reports focusing on the long-term outcomes after SMA resection are still limited.
Figure 1. Reconstruction of the superior mesenteric artery. (A) Basic anatomy of relevant vessels in SMA resection. (B) Direct end-to-end anastomosis. (C) Transposition of SpA to be anastomosed with the distal stump of the SMA. (D) End-to-end anastomosis with graft interposition. (E) Graft interposition from the aorta to the distal stump of the SMA. (F) Combined resection and reconstruction of the HA and SMA using interposition grafts. HA, hepatic artery, SpA, splenic artery, GDA, gastroduodenal artery, SMA, superior mesenteric artery, MCA, middle colic artery and LGA, left gastric artery.
Table 1. Previous reports about resection of the superior mesenteric artery.

3. Resection of the Hepatic Artery

Advanced cancers located at the pancreatic neck often invade the common and proper hepatic artery (HA), as well as the gastroduodenal artery (GDA). In such cases, segmental resection of the HA, including the root of the GDA, is suggested. If cancer invasion is limited and resected segment is short, end-to-end anastomosis is often possible. Recent guidelines have also described the combined HA or celiac axis (CA) resection as one of the putative options for LAPC [26]. Although a large series that specifically focuses on HA resection is limited, there are many small case series, including five to 20 patients who mainly underwent pancreaticoduodenectomy (PD) with concomitant resection of the HA until recently [13][6][9][14][15][16][17][19][20][21][22][27][28][29] (Table 2). Amano H et al. first reported a medium series of HA resections in which they described the details of techniques and outcomes about HA reconstruction. The in-hospital mortality rate was 7%, accompanied by an R0 rate of 80% and a median survival time (MST) of 12 months. The authors concluded that HA resection is justified only when surgery of R0 has taken place for selected patients with PC. Regarding the reconstruction technique of the HA, several reports described HA reconstruction, which was dominantly done by end-to-end anastomosis (Figure 2A,B) [14][15][16][17][20][21][22][27]. Short-segment resection of the HA was simple and safe and could be recommended as an entry procedure of AR for pancreatic surgeons who perform pancreatic head resection. In a case where the HA is resected in a long segment, arterial transposition (Figure 2C,D) [6][22] or interposition using the autograft to bridge between the celiac axis or aorta and proper HA is required (Figure 2E) [14][15][17][21]. To simplify and reduce the number of anastomoses, transposition of the SpA or colic artery should first be considered. The right inferior phrenic artery is an alternative option for a small orifice of the left HA. Although SpA transposition is usually performed with TP to gain enough length of the SpA pedicle, preservation of the pancreas tail would be possible if the left gastric artery (LGA) and great pancreatic artery are preserved. Desaki et al. reported a case series of SpA resection during PD mainly for PCs and documented that no clinically relevant splenic infarction was observed [30]. On the other hand, the omittance of HA reconstruction would be possible if we performed a specific preparation for HA resection. Miyazaki et al. proposed the novel management of HA resection with preoperative HA embolization to enhance the collateral hepatic arterial inflow [28]. After HA resection, backflow from the proper HA stump was observed. If the backflow was strong enough, they omitted HA reconstruction. In a 21-patient series, they reconstructed HA in only one patient, and eventually, 33% of the patients suffered postoperative liver infarction, but there was no in-hospital mortality.
Figure 2. Reconstruction of the hepatic artery. (A) Basic anatomy of the relevant vessels in HA resection. (B) Direct end-to-end anastomosis. (C) Transposition of the MCA and RIPA to be anastomosed with the RHA and LHA. (D) Transposition of the SpA to be anastomosed with the proper HA. (E) Graft interposition from the aorta to the stump of the proper HA. HA, hepatic artery, RIPA, right inferior phrenic artery, SpA, splenic artery, GDA, gastroduodenal artery, SMA, superior mesenteric artery, MCA, middle colic artery, LGA left gastric artery, RHA, right hepatic artery and LHA, left hepatic artery.
Table 2. Previous reports about resection of the hepatic artery.

4. Resection of the Celiac Axis

CA resection for advanced pancreatic body cancer was an exceptional situation of arterial resection, wherein reconstruction of the hepatic artery was considered to be unnecessary because of the peripancreatic collateral arterial flow that originated from the SMA [31]. Pancreatic body cancers frequently involve the celiac–hepatic artery system, and distal pancreatectomy with celiac axis resection (DP-CAR) was a reasonable choice to achieve an en-bloc eradication of the tumor and its invasion. The concept of DP-CAR was a modification of the Appleby procedure originally for advanced gastric cancers [31]. The first report about DP-CAR was written by Hishinuma et al. in 1991, and they documented the preservation of the whole stomach during CAR and distinguished DP-CAR from the Appleby procedure in that the stomach was preserved [32]. Afterward, several small series of DP-CARs were reported [33][34][35][36][37], and in 2007, Hirano et al. first described the short- and long-term outcomes of the standardized DP-CAR [38]. They reported 23 patients who underwent DP-CARs with no mortality and had acceptable overall survival (five-year survival rate, 42% and median survival time, 21 months). This pivotal report encouraged pancreatic surgeons worldwide to perform DP-CAR as a promising option to balance surgical and oncological safety. However, as the cases accumulated, ischemic complications involving the stomach or liver became prominent, as well as post-pancreatectomy hemorrhage, caused by the insufficient drainage of postoperative pancreatic fistula, leading to non-negligible mortality [39][40][41][42][43][44] (Table 3). Ischemic gastropathy or stomach perforation were complications specific to DP-CARs, which often included resection of the LGA, as well as the left gastroepiploic artery. Moreover, radical retroperitoneal dissection during DP-CAR includes resection of the left inferior phrenic artery. These sacrifices of critical gastric inflows potentially lead to life-threatening gastropathy [45]. As for liver infarction, collateral hepatic flow via the GDA was theoretically sufficient for liver perfusion. However, excessive dissection of the GDA sometimes leads to arterial stenosis, which causes depression of the hepatic arterial flow [46]. Depression of the proper hepatic artery induces recurrent cholangitis, liver abscess or cholecystitis. Cholecystitis was reported to be one possible cause of postoperative major intervention [40][45]. Therefore, the gallbladder should be resected routinely during DP-CAR. In the early years, preoperative arterial embolization of the HA or LGA to enhance the collateral flow was encouraged to avoid ischemic complications. However, recent reports found no positive impact of arterial embolization on the prevention of postoperative ischemic complications [45][46][47][48]. Another possible resolution is an intraoperative reconstruction of the LGA. Sato et al. first described reconstruction of the LGA to avoid ischemic gastropathy after DP-CAR [49]. The authors used a pedicle of the middle colic artery as an origin of the arterial supply. The right branch of the middle colic artery is usually away from the pancreatic body cancer and used as a suitable counterpart of the LGA. The efficacy of the anastomosis should be confirmed promptly and objectively after anastomosis. Oba et al. reported the intraoperative evaluation of the patency of LGA anastomosis using indocyanine green fluorescence imaging [50]. By these managements, the safety of DP-CARs would be improved.
Table 3. Previous reports of distal pancreatectomy with celiac axis resections (DP-CARs).

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