Abstract
Pancreatic cancer is a highly aggressive cancer with a rising incidence in most European coun-tries. Due to both the aggressive biology of the disease and the late diagnosis in many cases, pancreatic duct carcinoma is still a disease with a poor prognosis. Today, surgical resection of lo-calized tumor remains the only potentially cura-tive option available for these patients. Advances in surgical techniques and perioperative care has improved significantly in the last 20 years, causing an extension of indications for surgical intervention. However, despite new diagnostic techniques, the surgical exploration still plays the key role for the finally assessment of resect-ability. For evaluation of local resectability, lapa-roscopy alone cannot generally be recommended today and explorative laparotomy is required. Contraindications for pancreatic resection are liver metastasis, peritoneal metastasis, and tu¬mor infiltration of visceral arteries. The surgical management of pancreatic cancer consists of two phases: first, assessment of tumor resectability and second, if resectability is given, the pancreat-icoduodenectomy with consecutive reconstruc¬tion. Standard surgical strategies are the classic pancreaticoduodenectomy including a distal gastrectomy and the pylorus-preserving pancre-aticoduodenectomy (PPPD) preserving antral and pyloric function, respectively. Both surgical procedures are equally effective for the treat¬ment of pancreatic carcinoma. Delicate lymph-adenectomy during pancreaticoduodenectomy is important for radical oncological enforcement. An extended lymphadenectomy showed no ben¬efit in several trials. Despite the encouraging advances in surgical treatment, actuarial 5-year survival rates after pancreatic resection are only
at about 20%.
4.1 Introduction
The only curative approach for patients with pancreatic cancer is a radical resection of the tumor. The two standard resection procedures of choice are the resection of the pancreatic head and the left-sided pancreatic resection. In case of a local advanced pancreatic carcinoma, a total pancreatectomy may be advisable in se¬lected cases. During the last 30 years technical developments in pancreatic surgery significantly decreased the perioperative morbidity and mor-tality. Since pancreatic resections have become more accepted as a safe surgical procedure, two surgical approaches for patients with pancreatic head tumors are established today. The standard "Kausch-Whipple" pancreaticoduodenectomy and the pylorus-preserving pancreaticoduo-denectomy [11, 23, 45]. However, although the resection rate has increased and mortality de¬creased, the prognosis for patients with pancre¬atic cancer is still poor [15].
4.2 Assessment of Resectability
The preoperative clarification of resectability should only be performed via laparotomy. Ra-diological (CT/MRI) signs of involvement of the superior mesenteric-portal venous confluence are no contraindication for surgical exploration. Laparoscopic evaluations can only exclude peri-toneal carcinomatosis or liver metastasis, and therefore only provide incomplete information about the local resectability [14].
During the operation, the peritoneal cavity and its contents have to be carefully examined. Lesions suspicious of metastasis should be as-sessed histologically. Assessment of local expan-sion including vascular tumor involvement re-quires careful mobilization from the surrounding structures. Involvement of superior mesenteric artery (SMA), celiac trunk, or hepatic arteries precludes resection with curative intent, whereas invasion of the portal vein does not.
Preoperative or intraoperative biopsies are not obligatory to confirm the diagnosis of malig-nancy. If preoperative findings, the clinical pic-ture, and surgical findings are consistent, resec-tion should proceed.
4.3 Contraindications
for Pancreatic Resection
Due to the locally advanced nature of the disease and the presence of early metastases in the major-ity of patients, for only 20% of patients is curative resection feasible at the time of diagnosis [12]. However, if possible a radical resection of the tumor should be performed. In this context, not only the question of technical feasibility is impor¬tant, but more important should be the question of whether or not the patient will recover from the procedure. A definitive contraindication for a pancreaticoduodenectomy is the presence of local or distant metastases including peritoneal carcinomatosis. Metabolic disease is known as a significant predictor of short expected survival [3]. Further contraindications for radical sur¬gery are tumor invasion of the mesenteric root or invasion of visceral arteries (SMA, celiac axis or hepatic artery). Nowadays, cancer invasion of the superior mesenteric-portal venous conflu¬ence (SMPCV) is no longer a contraindication for radical pancreaticoduodenectomy [27]. It has to be mentioned that patients with concomitant severe disease should not be operated due to the significant increased mortality risk.
Because of declining surgical mortality rates after pancreatic resection, the role of palliative resections have been discussed in recent years.
Especially the question of whether a palliative pancreaticoduodenectomy should be offered to patients with hepatic metastases is still unan-swered (see also Chap. 13). Some data suggest that at least a selected group of patients may ben¬efit from palliative resections [25].
4.4 Surgical Technique
The "Kausch-Whipple" procedure is nowadays no longer regarded as the standard procedure. In recent years, pylorus-preserving pancreatoduo-denectomy (PPPD) was established as the stan¬dard resection procedure for periampullary ma¬lignancies. In contrast to the Whipple operation, which includes a 2/3 gastrectomy, the PPPD ne¬cessitates the preservation of the whole stomach, including the pylorus. The duodenum is usually cut about 2 cm distal from the pyloric ring.
After transverse laparotomy and Kocher ma-neuver (the mobilization of the duodenum), re-sectability in case of malignant disease has to be ascertained, and pancreatic head resection should be performed in a standard fashion, in-cluding dissection of the distal bile duct and en bloc dissection of the lymph nodes in the hepato-duodenal ligament and along the celiac trunk and superior mesenteric artery. After resection of the pancreatic head with the adjacent duodenum, the first jejunal loop has to be dissected and brought up through the mesocolon in a retrocolic fashion, after which an end-to-side pancreatojejunostomy has to be performed, then a choledochojejunos-tomy, and finally a duodenojejunostomy.
In the past, several reports attempted to com-pare the standard Whipple to the pylorus-pre-serving procedure, also emphasizing that the operating time for PPPD is shorter [24]. Some authors have reported a higher rate of postopera-tive delayed gastric emptying after PPPD [49]. A prospective randomized multicenter study that compared the pylorus-preserving pancreatico-duodenectomy and standard Whipple operation with regard to duration of surgery, blood loss, hospital stay, delayed gastric emptying, and sur¬vival showed no significant differences in median blood loss and duration of operation. This study showed only a marginal difference in postopera¬tive weight loss after the standard Whipple pro¬
cedure. The overall long-term and disease-free survival was comparable for both procedures [43]. To date, the choice between both surgi¬cal procedures, standard Whipple procedure or pylorus-preserving pancreaticoduodenectomy, cannot be made on evidence-based data. How-ever, PPPD is the preferred approach for patients with pancreatic head carcinoma today. Most im-portant, the pylorus-preserving pancreaticoduo-denectomy is a safe and radical operation that does not affect prognosis [40].
The standard procedure for surgical treatment of carcinomas of the pancreatic body or pancre-atic tail is a pancreatic left resection. Due to a late onset of clinical signs such as jaundice or pain, left-sided pancreatic tumors are characterized mostly by an advanced stage at diagnosis.
After transverse laparotomy, the pancreatic left resection should be performed, based on (1) the principles of surgical oncology as a no-touch-technique and (2) standard en bloc dissection of the peripancreatic lymph nodes, including sple-nectomy. Depending on the dimension of the tumor, the resection margin has to be extended to reach the pancreatic head to enable tumor-free resection margins (subtotal, left-sided pan¬createctomy). The pancreatic remnant should be provided by an end-to-side pancreatojejunos-tomy to avoid pancreatic fistula.
One attempt to improve the prognosis of pan-creatic cancer was to perform more aggressive
4.5
surgical approaches such as a total pancreatec-tomy [32]. Theoretical advantages for this proce-dure are that total pancreatectomy prevents the risk of pancreatic fistulas and provides a radical eradication of the tumor [20]. Furthermore, the risk of positive resection margins in the pancre¬atic remnant seemed to be eliminated. However, the experiences of the last 20 years has shown that postoperative complications are more fre¬quent after total pancreatectomy compared to partial pancreaticoduodenectomy. One problem is severe diabetes mellitus, which is often dif¬ficult to manage. Baumel et al. reported on dif¬ficulties in glucoregulation in up to 25% of pa¬tients after total pancreatectomy [3]. Nowadays a total pancreatectomy is no longer an option for carcinomas of the pancreatic head. However, in individual cases, e.g., in case of multicentric car-cinomas, an indication for total pancreatectomy may be given.
Pancreaticoenteric Anastomosis
The operative resection of pancreatic cancer in-cludes cautious handling of the pancreatic rem-nant. For that, the texture and size of the rem¬nant has to be taken into surgical consideration [46]. To prevent fatal complications such as, e.g., a leakage from the pancreaticojejunal anastomo¬sis, different anastomotic techniques have been
published during recent years (Figs. 4.1, 4.2, and 4.3). To date, however, it is still not possible to decide which anastomotic technique is the best. A standard anastomotic technique is the duct-to-mucosa pancreaticojejunostomy described by Cattell and modified by Braasch [6, 7]. After re¬moval of an area of serosa matching the cut sur¬face of the pancreas, the back wall has to be su¬tured with a running suture (4-0 PDS), the bowel wall incised, and a duct-to-mucosa anastomosis performed with single stitches (5-0 Monocryl). After completion of the back wall, the front wall of the duct-to-mucosa anastomosis must also be applied with 5-0 Monocryl single stitches. Sub¬sequently, the anterior wall of the anastomosis to the bowel has to be completed with a 4-0 PDS running suture.
A further technique is the so-called mattress technique. An incision, the same size as the pan-creatic cut surface, has to be placed in the jeju-nal loop. Then U-stitches (4-0 PDS), starting at the jejunal back wall, from back to front, have to be positioned straight through the pancreatic remnant about 1 cm distal from the cut surface
and then through the front wall of the jejunal loop. With this technique the pancreatic rem¬nant is completely enclosed by the jejunal loop. A prospective, randomized trail comparing both techniques has shown that both techniques yield similar incidences of complications. The mattress technique seems, therefore, to be more suitable for training schedules in pancreatic surgery [26].
4.6 Pancreatogastrostomy
The pancreaticoenteric anastomosis is known as the "Achilles heel" of pancreatic surgery. Due to this perception, several approaches have been at-tempted to improve the safety of this anastomosis. One strategy was the introduction of a pancrea-togastrostomy as an alternative reconstruction technique after pancreatic head resection [30]. Three different principles to achieve pancreato¬gastrostomy are in use today: the implantation of the pancreatic remnant into the stomach, the implantation of only the pancreatic duct into the stomach, and an anastomosis between the pan¬creatic duct and the gastric mucosa. However, the first is by far the most often performed pro¬cedure. A view through the literature shows that the surgical results after pancreatogastrostomy are similar to those yielded with pancreaticoje-junostomy [2, 21, 29]. It is known that long-term pancreatic secretion into the stomach causes al¬kaline juice, which affects the gastric mucosa. To date, however, there is no substantial data show¬ing a correlation between an increased risk of peptic ulcers and pancreatogastric anastomosis. Interestingly, a study by Hyodo et al. showed that pancreatogastrostomy appears to decrease the grade of Helicobacter pylori infection, and tends to ameliorate the severity of gastritis after pan-creatogastrostomy [19]. Taken together, to date there is no convincing data that the pancreatic fluid is harmful to the stomach.
4.7 Lymphadenectomy
Affection of lymph nodes is reported to be found in more than 70% of patients after resection [4]. A radical lymphadenectomy along the hepatodu-odenal ligament, celiac trunk, and superior mes-enteric artery should be performed routinely as standard technique. However, to improve long-term survival in patients with pancreatic cancer, more radical surgical procedures had been pro¬posed. One of these approaches is the extended lymph node dissection, which includes resection of bilateral paraaortal lymphatic tissue from the diaphragm down to the inferior mesenteric ar¬tery and laterally to the hilum of the right kidney [37]. Several recent studies indicated a variability in results regarding the influence of an extended lymph node clearance (Table 4.1). In a prospec-tive randomized trail, Nimura et al. compared 51 patients after standard lymphadenectomy and 50 patients after extended lymph node dissection. No differences were found in overall survival, survival for pN0/pN1, tumor recurrence, body weight, quality of life, and bowel movements [35]. Connor et al. demonstrated that meta¬static involvement of lymph node 8a (located at the common hepatic artery) is an indepen¬dent prognostic factor after pylorus-preserving resection [8]. Two further randomized studies of extended lymph node dissection reported a similar overall morbidity, although the study from Baltimore reported on an increased rate of delayed gastric emptying [36, 47]. Henne-Bruns et al. showed no differences in survival compar-ing standard and extended lymph node dissec-tion, and concluded that further improvement of the survival rate cannot be achieved by ex¬tended retroperitoneal lymphadenectomy [17]. In conclusion, there is no evidence as yet that an extended lymph node dissection positively influ-ences survival.
4.8 Portal Vein Resection
Tumor invasion of the portal or superior mesen-teric vein has always been a controversial issue in pancreatic surgery. In only a small percentage of patients suffering from pancreatic cancer, the surgical goal of tumor-free resection margins is limited by venous tumor invasion. For these patients a radical surgical approach, including the resection of portal vein or superior mesen-teric vein, is the only chance of achieving an R0-situation. In 1951, Moore et al. were the first to describe a resection of the superior mesenteric vein for pancreatic cancer [31]. In 1973, Fortner performed the successful en bloc removal for car¬cinoma of the pancreas combined with the resec¬tion and reconstruction of the portal vein, the so-called "regional pancreatectomy" [13].
Several of the technical procedures are: tan-gential resection and venous patch-plastic, seg-mental resection with splenic vein ligation, and primary anastomosis or splenic vein ligation and graft interposition. Further procedures may be the segmental resection with splenic vein preser¬vation either with primary anastomosis or again with graft interposition. In the literature the sur¬gical technique for resection and reconstruction is well established as a safe procedure [9, 39]. Due to this fact, cancer invasion of the mesen¬teric-portal venous axis should not be considered a contraindication for radical pancreaticoduode-nectomy any more.
Pathological assessments of resected veins confirmed cancerous venous invasion in 20%-70% of resected specimens [5, 42]. These data indicate that a significant percentage of patients with suspected venous tumor invasion only show an inflammatory adherence. Some authors reported on small patient cohorts undergoing portal vein resection combined with arterial resection [33, 38, 44]. However, combined resec¬tions of the portal vein and visceral arteries have not yet been established as a standard technique, and therefore such procedures are only indi¬cated in highly selected patients and should be performed as part of clinical study protocols only.
4.9 Preoperative Stenting
The significance of preoperative biliary stenting (Table 4.2) in jaundiced patients prior to pan-creaticoduodenectomy has been under discus¬sion for many years. It is well known that severe jaundice can cause multi-organ dysfunction and defects in immune function [18]. A long-term biliary tract obstruction can lead to biliary tract sepsis and septic shock. Furthermore, a correla¬tion between obstructive jaundice and operative morbidity and mortality could be demonstrated [1]. However, studies in the more recent past showed that short-term preoperative biliary de¬compression does not improve surgical results after pancreatic head resection [34]. Several
retrospective and prospective reviews have failed to show a significant reduction of length of hos-pital stay or morbidity after preoperative biliary drainage [22, 41]. There are some indicators that preoperative stenting increases the rate of wound infections and can contaminate bile after instru-mentation of the bile duct [41]. In conclusion, preoperative stenting is not indicated generally today in jaundiced patients due to pancreatic head tumor formation, and therefore it should only be used selectively.
4.10 Octreotide
The octapeptide analog of somatostatin, octreo-tide, has been proposed to reduce the incidence of pancreatic fistulas after pancreatic resections. While octreotide is already successfully in use for the prevention of pancreatitis and pancre¬atic fistulas after pancreatic transplantation [10], the role of somatostatin as prophylaxis against pancreatic anastomosis leakage is still under debate. Several randomized studies on the role of somatostatin have been published in recent years. All of the studies failed to show a signifi¬cant difference in postoperative mortality. On the one hand, studies published between 1992 and 1995 showed fewer complications in patients receiving octreotide; on the other hand, in a se¬ries published between 1997 and 2002, less or no differences were seen. Only one study showed a decreased rate of postoperative pancreatic fis¬tulas in patients after octreotide treatment [16]. Li-Ling and colleagues published a systematic review analyzing whether the use of octreotide is effective in the prevention of postoperative pan¬creatic complications. The analysis suggested that in centers with a high fistula rate octreotide ad¬ministration reduces the rate of major complica¬tions [28]. In summary, octreotide appears to de¬crease the overall morbidity and the incidence of pancreatic fistulas after pancreatic resections, but not mortality. Due to this fact, octreotide may be indicated especially in patients with nonfibrotic pancreatic glands or in patients with nondilated ducts undergoing pancreatic resection.
4.11 Summary
Pancreatic cancer is the fifth leading cause of cancer mortality, with a rising incidence in most European countries. Due to both the aggressive biology of the disease and the late diagnosis in many cases, ductal pancreatic carcinoma is still a disease with a poor prognosis. Today, surgical resection of localized tumor remains the only potentially curative option available for these pa-tients. Advances in surgical technique and peri-operative care has improved significantly during last 20 years, causing an extension of indications for surgical intervention. Resections in elderly patients or removal of advanced tumors includ¬ing portal vein resections are nowadays feasible with low perioperative mortality rates. Although the spectrum of indication has increased, opera¬tive mortality rates today for pancreaticoduode-nectomy should not exceed 5% at centers with a high caseload. Despite new diagnostic tech¬niques, however, surgical exploration still plays the key role for final assessment of resectability. In this context, the role of diagnostic laparos-copy in patients with pancreatic malignancies is controversial. For detection of liver or peritoneal metastasis laparoscopy before laparotomy may be reasonable. For evaluation of local resectability, laparoscopy alone can generally not be recom-mended nowadays, and explorative laparotomy should be performed.
Contraindications for pancreatic resection are liver metastasis, peritoneal metastasis, and tumor infiltration of visceral arteries. The two phases of surgical management of pancreatic cancer are: assessment of tumor resectability and, if resectability is given, the pancreaticoduodenec-tomy with consecutive reconstruction. Standard surgical strategies are the classic pancreatico-duodenectomy including a distal gastrectomy or PPPD, preserving antral and pyloric func¬tion respectively. Both surgical procedures are equally effective for the treatment of pancreatic carcinoma. Delicate lymphadenectomy during pancreaticoduodenectomy is important for radi-cal oncological enforcement. In several trials, ex-tended lymphadenectomy showed no significant benefits and is still under discussion. Despite the encouraging advances in surgical treatment, ac-tuarial 5-year survival rates after pancreatic re-section are only at about 20% [48].
Pancreatic cancer is a highly aggressive cancer with a rising incidence in most European coun-tries. Due to both the aggressive biology of the disease and the late diagnosis in many cases, pancreatic duct carcinoma is still a disease with a poor prognosis. Today, surgical resection of lo-calized tumor remains the only potentially cura-tive option available for these patients. Advances in surgical techniques and perioperative care has improved significantly in the last 20 years, causing an extension of indications for surgical intervention. However, despite new diagnostic techniques, the surgical exploration still plays the key role for the finally assessment of resect-ability. For evaluation of local resectability, lapa-roscopy alone cannot generally be recommended today and explorative laparotomy is required. Contraindications for pancreatic resection are liver metastasis, peritoneal metastasis, and tu¬mor infiltration of visceral arteries. The surgical management of pancreatic cancer consists of two phases: first, assessment of tumor resectability and second, if resectability is given, the pancreat-icoduodenectomy with consecutive reconstruc¬tion. Standard surgical strategies are the classic pancreaticoduodenectomy including a distal gastrectomy and the pylorus-preserving pancre-aticoduodenectomy (PPPD) preserving antral and pyloric function, respectively. Both surgical procedures are equally effective for the treat¬ment of pancreatic carcinoma. Delicate lymph-adenectomy during pancreaticoduodenectomy is important for radical oncological enforcement. An extended lymphadenectomy showed no ben¬efit in several trials. Despite the encouraging advances in surgical treatment, actuarial 5-year survival rates after pancreatic resection are only
at about 20%.
4.1 Introduction
The only curative approach for patients with pancreatic cancer is a radical resection of the tumor. The two standard resection procedures of choice are the resection of the pancreatic head and the left-sided pancreatic resection. In case of a local advanced pancreatic carcinoma, a total pancreatectomy may be advisable in se¬lected cases. During the last 30 years technical developments in pancreatic surgery significantly decreased the perioperative morbidity and mor-tality. Since pancreatic resections have become more accepted as a safe surgical procedure, two surgical approaches for patients with pancreatic head tumors are established today. The standard "Kausch-Whipple" pancreaticoduodenectomy and the pylorus-preserving pancreaticoduo-denectomy [11, 23, 45]. However, although the resection rate has increased and mortality de¬creased, the prognosis for patients with pancre¬atic cancer is still poor [15].
4.2 Assessment of Resectability
The preoperative clarification of resectability should only be performed via laparotomy. Ra-diological (CT/MRI) signs of involvement of the superior mesenteric-portal venous confluence are no contraindication for surgical exploration. Laparoscopic evaluations can only exclude peri-toneal carcinomatosis or liver metastasis, and therefore only provide incomplete information about the local resectability [14].
During the operation, the peritoneal cavity and its contents have to be carefully examined. Lesions suspicious of metastasis should be as-sessed histologically. Assessment of local expan-sion including vascular tumor involvement re-quires careful mobilization from the surrounding structures. Involvement of superior mesenteric artery (SMA), celiac trunk, or hepatic arteries precludes resection with curative intent, whereas invasion of the portal vein does not.
Preoperative or intraoperative biopsies are not obligatory to confirm the diagnosis of malig-nancy. If preoperative findings, the clinical pic-ture, and surgical findings are consistent, resec-tion should proceed.
4.3 Contraindications
for Pancreatic Resection
Due to the locally advanced nature of the disease and the presence of early metastases in the major-ity of patients, for only 20% of patients is curative resection feasible at the time of diagnosis [12]. However, if possible a radical resection of the tumor should be performed. In this context, not only the question of technical feasibility is impor¬tant, but more important should be the question of whether or not the patient will recover from the procedure. A definitive contraindication for a pancreaticoduodenectomy is the presence of local or distant metastases including peritoneal carcinomatosis. Metabolic disease is known as a significant predictor of short expected survival [3]. Further contraindications for radical sur¬gery are tumor invasion of the mesenteric root or invasion of visceral arteries (SMA, celiac axis or hepatic artery). Nowadays, cancer invasion of the superior mesenteric-portal venous conflu¬ence (SMPCV) is no longer a contraindication for radical pancreaticoduodenectomy [27]. It has to be mentioned that patients with concomitant severe disease should not be operated due to the significant increased mortality risk.
Because of declining surgical mortality rates after pancreatic resection, the role of palliative resections have been discussed in recent years.
Especially the question of whether a palliative pancreaticoduodenectomy should be offered to patients with hepatic metastases is still unan-swered (see also Chap. 13). Some data suggest that at least a selected group of patients may ben¬efit from palliative resections [25].
4.4 Surgical Technique
The "Kausch-Whipple" procedure is nowadays no longer regarded as the standard procedure. In recent years, pylorus-preserving pancreatoduo-denectomy (PPPD) was established as the stan¬dard resection procedure for periampullary ma¬lignancies. In contrast to the Whipple operation, which includes a 2/3 gastrectomy, the PPPD ne¬cessitates the preservation of the whole stomach, including the pylorus. The duodenum is usually cut about 2 cm distal from the pyloric ring.
After transverse laparotomy and Kocher ma-neuver (the mobilization of the duodenum), re-sectability in case of malignant disease has to be ascertained, and pancreatic head resection should be performed in a standard fashion, in-cluding dissection of the distal bile duct and en bloc dissection of the lymph nodes in the hepato-duodenal ligament and along the celiac trunk and superior mesenteric artery. After resection of the pancreatic head with the adjacent duodenum, the first jejunal loop has to be dissected and brought up through the mesocolon in a retrocolic fashion, after which an end-to-side pancreatojejunostomy has to be performed, then a choledochojejunos-tomy, and finally a duodenojejunostomy.
In the past, several reports attempted to com-pare the standard Whipple to the pylorus-pre-serving procedure, also emphasizing that the operating time for PPPD is shorter [24]. Some authors have reported a higher rate of postopera-tive delayed gastric emptying after PPPD [49]. A prospective randomized multicenter study that compared the pylorus-preserving pancreatico-duodenectomy and standard Whipple operation with regard to duration of surgery, blood loss, hospital stay, delayed gastric emptying, and sur¬vival showed no significant differences in median blood loss and duration of operation. This study showed only a marginal difference in postopera¬tive weight loss after the standard Whipple pro¬
cedure. The overall long-term and disease-free survival was comparable for both procedures [43]. To date, the choice between both surgi¬cal procedures, standard Whipple procedure or pylorus-preserving pancreaticoduodenectomy, cannot be made on evidence-based data. How-ever, PPPD is the preferred approach for patients with pancreatic head carcinoma today. Most im-portant, the pylorus-preserving pancreaticoduo-denectomy is a safe and radical operation that does not affect prognosis [40].
The standard procedure for surgical treatment of carcinomas of the pancreatic body or pancre-atic tail is a pancreatic left resection. Due to a late onset of clinical signs such as jaundice or pain, left-sided pancreatic tumors are characterized mostly by an advanced stage at diagnosis.
After transverse laparotomy, the pancreatic left resection should be performed, based on (1) the principles of surgical oncology as a no-touch-technique and (2) standard en bloc dissection of the peripancreatic lymph nodes, including sple-nectomy. Depending on the dimension of the tumor, the resection margin has to be extended to reach the pancreatic head to enable tumor-free resection margins (subtotal, left-sided pan¬createctomy). The pancreatic remnant should be provided by an end-to-side pancreatojejunos-tomy to avoid pancreatic fistula.
One attempt to improve the prognosis of pan-creatic cancer was to perform more aggressive
4.5
surgical approaches such as a total pancreatec-tomy [32]. Theoretical advantages for this proce-dure are that total pancreatectomy prevents the risk of pancreatic fistulas and provides a radical eradication of the tumor [20]. Furthermore, the risk of positive resection margins in the pancre¬atic remnant seemed to be eliminated. However, the experiences of the last 20 years has shown that postoperative complications are more fre¬quent after total pancreatectomy compared to partial pancreaticoduodenectomy. One problem is severe diabetes mellitus, which is often dif¬ficult to manage. Baumel et al. reported on dif¬ficulties in glucoregulation in up to 25% of pa¬tients after total pancreatectomy [3]. Nowadays a total pancreatectomy is no longer an option for carcinomas of the pancreatic head. However, in individual cases, e.g., in case of multicentric car-cinomas, an indication for total pancreatectomy may be given.
Pancreaticoenteric Anastomosis
The operative resection of pancreatic cancer in-cludes cautious handling of the pancreatic rem-nant. For that, the texture and size of the rem¬nant has to be taken into surgical consideration [46]. To prevent fatal complications such as, e.g., a leakage from the pancreaticojejunal anastomo¬sis, different anastomotic techniques have been
published during recent years (Figs. 4.1, 4.2, and 4.3). To date, however, it is still not possible to decide which anastomotic technique is the best. A standard anastomotic technique is the duct-to-mucosa pancreaticojejunostomy described by Cattell and modified by Braasch [6, 7]. After re¬moval of an area of serosa matching the cut sur¬face of the pancreas, the back wall has to be su¬tured with a running suture (4-0 PDS), the bowel wall incised, and a duct-to-mucosa anastomosis performed with single stitches (5-0 Monocryl). After completion of the back wall, the front wall of the duct-to-mucosa anastomosis must also be applied with 5-0 Monocryl single stitches. Sub¬sequently, the anterior wall of the anastomosis to the bowel has to be completed with a 4-0 PDS running suture.
A further technique is the so-called mattress technique. An incision, the same size as the pan-creatic cut surface, has to be placed in the jeju-nal loop. Then U-stitches (4-0 PDS), starting at the jejunal back wall, from back to front, have to be positioned straight through the pancreatic remnant about 1 cm distal from the cut surface
and then through the front wall of the jejunal loop. With this technique the pancreatic rem¬nant is completely enclosed by the jejunal loop. A prospective, randomized trail comparing both techniques has shown that both techniques yield similar incidences of complications. The mattress technique seems, therefore, to be more suitable for training schedules in pancreatic surgery [26].
4.6 Pancreatogastrostomy
The pancreaticoenteric anastomosis is known as the "Achilles heel" of pancreatic surgery. Due to this perception, several approaches have been at-tempted to improve the safety of this anastomosis. One strategy was the introduction of a pancrea-togastrostomy as an alternative reconstruction technique after pancreatic head resection [30]. Three different principles to achieve pancreato¬gastrostomy are in use today: the implantation of the pancreatic remnant into the stomach, the implantation of only the pancreatic duct into the stomach, and an anastomosis between the pan¬creatic duct and the gastric mucosa. However, the first is by far the most often performed pro¬cedure. A view through the literature shows that the surgical results after pancreatogastrostomy are similar to those yielded with pancreaticoje-junostomy [2, 21, 29]. It is known that long-term pancreatic secretion into the stomach causes al¬kaline juice, which affects the gastric mucosa. To date, however, there is no substantial data show¬ing a correlation between an increased risk of peptic ulcers and pancreatogastric anastomosis. Interestingly, a study by Hyodo et al. showed that pancreatogastrostomy appears to decrease the grade of Helicobacter pylori infection, and tends to ameliorate the severity of gastritis after pan-creatogastrostomy [19]. Taken together, to date there is no convincing data that the pancreatic fluid is harmful to the stomach.
4.7 Lymphadenectomy
Affection of lymph nodes is reported to be found in more than 70% of patients after resection [4]. A radical lymphadenectomy along the hepatodu-odenal ligament, celiac trunk, and superior mes-enteric artery should be performed routinely as standard technique. However, to improve long-term survival in patients with pancreatic cancer, more radical surgical procedures had been pro¬posed. One of these approaches is the extended lymph node dissection, which includes resection of bilateral paraaortal lymphatic tissue from the diaphragm down to the inferior mesenteric ar¬tery and laterally to the hilum of the right kidney [37]. Several recent studies indicated a variability in results regarding the influence of an extended lymph node clearance (Table 4.1). In a prospec-tive randomized trail, Nimura et al. compared 51 patients after standard lymphadenectomy and 50 patients after extended lymph node dissection. No differences were found in overall survival, survival for pN0/pN1, tumor recurrence, body weight, quality of life, and bowel movements [35]. Connor et al. demonstrated that meta¬static involvement of lymph node 8a (located at the common hepatic artery) is an indepen¬dent prognostic factor after pylorus-preserving resection [8]. Two further randomized studies of extended lymph node dissection reported a similar overall morbidity, although the study from Baltimore reported on an increased rate of delayed gastric emptying [36, 47]. Henne-Bruns et al. showed no differences in survival compar-ing standard and extended lymph node dissec-tion, and concluded that further improvement of the survival rate cannot be achieved by ex¬tended retroperitoneal lymphadenectomy [17]. In conclusion, there is no evidence as yet that an extended lymph node dissection positively influ-ences survival.
4.8 Portal Vein Resection
Tumor invasion of the portal or superior mesen-teric vein has always been a controversial issue in pancreatic surgery. In only a small percentage of patients suffering from pancreatic cancer, the surgical goal of tumor-free resection margins is limited by venous tumor invasion. For these patients a radical surgical approach, including the resection of portal vein or superior mesen-teric vein, is the only chance of achieving an R0-situation. In 1951, Moore et al. were the first to describe a resection of the superior mesenteric vein for pancreatic cancer [31]. In 1973, Fortner performed the successful en bloc removal for car¬cinoma of the pancreas combined with the resec¬tion and reconstruction of the portal vein, the so-called "regional pancreatectomy" [13].
Several of the technical procedures are: tan-gential resection and venous patch-plastic, seg-mental resection with splenic vein ligation, and primary anastomosis or splenic vein ligation and graft interposition. Further procedures may be the segmental resection with splenic vein preser¬vation either with primary anastomosis or again with graft interposition. In the literature the sur¬gical technique for resection and reconstruction is well established as a safe procedure [9, 39]. Due to this fact, cancer invasion of the mesen¬teric-portal venous axis should not be considered a contraindication for radical pancreaticoduode-nectomy any more.
Pathological assessments of resected veins confirmed cancerous venous invasion in 20%-70% of resected specimens [5, 42]. These data indicate that a significant percentage of patients with suspected venous tumor invasion only show an inflammatory adherence. Some authors reported on small patient cohorts undergoing portal vein resection combined with arterial resection [33, 38, 44]. However, combined resec¬tions of the portal vein and visceral arteries have not yet been established as a standard technique, and therefore such procedures are only indi¬cated in highly selected patients and should be performed as part of clinical study protocols only.
4.9 Preoperative Stenting
The significance of preoperative biliary stenting (Table 4.2) in jaundiced patients prior to pan-creaticoduodenectomy has been under discus¬sion for many years. It is well known that severe jaundice can cause multi-organ dysfunction and defects in immune function [18]. A long-term biliary tract obstruction can lead to biliary tract sepsis and septic shock. Furthermore, a correla¬tion between obstructive jaundice and operative morbidity and mortality could be demonstrated [1]. However, studies in the more recent past showed that short-term preoperative biliary de¬compression does not improve surgical results after pancreatic head resection [34]. Several
retrospective and prospective reviews have failed to show a significant reduction of length of hos-pital stay or morbidity after preoperative biliary drainage [22, 41]. There are some indicators that preoperative stenting increases the rate of wound infections and can contaminate bile after instru-mentation of the bile duct [41]. In conclusion, preoperative stenting is not indicated generally today in jaundiced patients due to pancreatic head tumor formation, and therefore it should only be used selectively.
4.10 Octreotide
The octapeptide analog of somatostatin, octreo-tide, has been proposed to reduce the incidence of pancreatic fistulas after pancreatic resections. While octreotide is already successfully in use for the prevention of pancreatitis and pancre¬atic fistulas after pancreatic transplantation [10], the role of somatostatin as prophylaxis against pancreatic anastomosis leakage is still under debate. Several randomized studies on the role of somatostatin have been published in recent years. All of the studies failed to show a signifi¬cant difference in postoperative mortality. On the one hand, studies published between 1992 and 1995 showed fewer complications in patients receiving octreotide; on the other hand, in a se¬ries published between 1997 and 2002, less or no differences were seen. Only one study showed a decreased rate of postoperative pancreatic fis¬tulas in patients after octreotide treatment [16]. Li-Ling and colleagues published a systematic review analyzing whether the use of octreotide is effective in the prevention of postoperative pan¬creatic complications. The analysis suggested that in centers with a high fistula rate octreotide ad¬ministration reduces the rate of major complica¬tions [28]. In summary, octreotide appears to de¬crease the overall morbidity and the incidence of pancreatic fistulas after pancreatic resections, but not mortality. Due to this fact, octreotide may be indicated especially in patients with nonfibrotic pancreatic glands or in patients with nondilated ducts undergoing pancreatic resection.
4.11 Summary
Pancreatic cancer is the fifth leading cause of cancer mortality, with a rising incidence in most European countries. Due to both the aggressive biology of the disease and the late diagnosis in many cases, ductal pancreatic carcinoma is still a disease with a poor prognosis. Today, surgical resection of localized tumor remains the only potentially curative option available for these pa-tients. Advances in surgical technique and peri-operative care has improved significantly during last 20 years, causing an extension of indications for surgical intervention. Resections in elderly patients or removal of advanced tumors includ¬ing portal vein resections are nowadays feasible with low perioperative mortality rates. Although the spectrum of indication has increased, opera¬tive mortality rates today for pancreaticoduode-nectomy should not exceed 5% at centers with a high caseload. Despite new diagnostic tech¬niques, however, surgical exploration still plays the key role for final assessment of resectability. In this context, the role of diagnostic laparos-copy in patients with pancreatic malignancies is controversial. For detection of liver or peritoneal metastasis laparoscopy before laparotomy may be reasonable. For evaluation of local resectability, laparoscopy alone can generally not be recom-mended nowadays, and explorative laparotomy should be performed.
Contraindications for pancreatic resection are liver metastasis, peritoneal metastasis, and tumor infiltration of visceral arteries. The two phases of surgical management of pancreatic cancer are: assessment of tumor resectability and, if resectability is given, the pancreaticoduodenec-tomy with consecutive reconstruction. Standard surgical strategies are the classic pancreatico-duodenectomy including a distal gastrectomy or PPPD, preserving antral and pyloric func¬tion respectively. Both surgical procedures are equally effective for the treatment of pancreatic carcinoma. Delicate lymphadenectomy during pancreaticoduodenectomy is important for radi-cal oncological enforcement. In several trials, ex-tended lymphadenectomy showed no significant benefits and is still under discussion. Despite the encouraging advances in surgical treatment, ac-tuarial 5-year survival rates after pancreatic re-section are only at about 20% [48].
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