At present, although the level of pancreatic cancer diagnosis and treatment has made great progress, however, due to the special biological behavior of pancreatic cancer, which presents the characteristics of infiltrative growth and distant metastasis at an early stage, only about 30% of patients are feasible to undergo local or regional resection.
Currently, the 5-year survival rate of pancreatic cancer is still maintained at 5%-6%. Although there are various factors affecting the prognosis of pancreatic cancer, it is indisputable that radical resection of the tumor is of great importance to prolong the survival and improve the prognosis of patients. Given the limited number of available studies and the fact that the scope of resection and the area of lymph node dissection vary from study to study, the International Study Group for Pancreatic Surgery (ISGPS) suggests that there is an urgent need to reach a consensus on the definition and scope of pancreatic resection to provide appropriate standards and guidance for the surgical treatment of pancreatic cancer.
In April 2013, the ISGPS held a workshop in Verona, Italy, to summarize and analyze the prospective and retrospective studies on pancreatic cancer in Pubmed and Embase databases, and to reach a consensus on standard pancreatic resection, extended pancreatic resection and standard lymph node dissection, so as to lay a good foundation for better international collaboration and in-depth communication in the future. The theoretical basis for better international collaboration and in-depth communication in the future.
In this meeting, the following issues were discussed: (1) the scope of standard pancreatic resection; (2) the scope of expanded pancreatic resection; (3) the nomenclature of pancreatic surgical lymph nodes; (4) the scope of standard lymph node dissection for pancreatic cancer; and (5) the choice of standard and expanded pancreatic resection. In this article, we interpret the main issues involved in the consensus, aiming to provide some reference and reference for clinicians performing pancreatic cancer resection.
I. Standard scope of pancreatic resection
1. Pancreaticoduodenectomy
(1) head of pancreas and hook; (2) duodenum and beginning of jejunum; (3) common bile duct and gallbladder; (4) lymph node dissection; (5) pylorus and/or gastric sinus if necessary; (6) transverse mesenteric resection without vascular area if necessary (e.g. soft tissue connected with tumor, but not including the colon itself).
2. Standard distal pancreatectomy
(1) pancreatic body and/or tail; (2) spleen and splenic vessels; (3) lymph node dissection; (4) left anterior renal fascia resection if necessary; (5) transverse mesenteric resection in avascular area if necessary (e.g. soft tissues attached to the tumor, but not the colon itself).
3. Standard total pancreatectomy
(1) head, neck, body and tail of pancreas; (2) beginning of duodenum and jejunum; (3) common bile duct and gallbladder; (4) spleen and splenic vessels; (5) lymph node dissection; (6) pylorus and/or sinus resection if necessary; (7) resection of anterior renal fascia if necessary; (8) transverse mesocolic resection in avascular area if necessary (e.g. soft tissues attached to the tumor, but not the colon itself). (8) transverse colon mesenterectomy (such as soft tissue attached to the tumor, but not the colon itself) if necessary.
The scope of extended pancreatectomy
Each center has its own criteria for the definition of extended resection. In addition to the standard surgical scope of resection described above, the following components are mainly included: (1) the colon. The pancreatic tumor is close to or easily invades the transverse colonic mesentery and/or the colonic mesenteric root. (2) Blood vessels. For tumors in the head or body of the pancreas, the proportion of combined vascular resections is increasing, including the celiac trunk, hepatic artery and/or superior mesenteric artery in addition to resection of the portal vein and superior mesenteric vein. (3) Liver. Pancreatic cancer is prone to directly invade the liver, and ISGPS states: clearly distinguish metastatic tumors in the liver and perform pancreatic resection combined with resection of local metastases in the liver, which is not an extended pancreatectomy. (4) Adrenal gland. For tumors in the tail of the pancreatic body involving the left adrenal gland, combined with resection of the left adrenal gland during distal pancreatectomy, it is an extended pancreatectomy. (5) Lymph nodes: For a long time, enlarged lymph node dissection has been classified as enlarged pancreatic resection. The ISGPS recommends that since enlarged pancreatic resection emphasizes the removal of local organs, enlarged lymph node dissection alone does not belong to enlarged pancreatic resection and is only defined as “enlarged lymph node dissection”. Based on the results of the conference, the surgical scope of extended pancreatectomy is outlined below.
1. Extended pancreaticoduodenectomy
This procedure is based on standard pancreaticoduodenectomy in combination with resection of one or more of the following organs: (1) distal stomach beyond the gastric sinus or more than half of it; (2) colon and/or colonic mesentery, with vascularized transverse colonic mesentery (vessels mainly include: ileocolic, right colonic, or mesocolic vessels); (3) small intestine distal to the beginning of the jejunum; (4) portal vein, superior mesenteric vein, and/or (or) inferior mesenteric vein; (5) hepatic artery, celiac trunk, and/or superior mesenteric artery; (6) inferior vena cava; (7) right adrenal gland; (8) right kidney and/or right renal vessels; (9) liver; and (10) diaphragm angle.
2. Extended distal pancreatectomy
In addition to the standard distal pancreatectomy, one or more of the following organs are included: (1) other parts of the gastrectomy; (2) colon and/or colonic mesentery with vascularized transverse colonic mesentery (vessels include mainly: mesocolonic or left colonic vessels); (3) small intestine; (4) portal vein, superior mesenteric vein and/or inferior mesenteric vein; (5) hepatic artery, abdominal trunk and/or superior mesenteric artery; (6) inferior vena cava; (7) left adrenal gland; (8) left kidney and/or left renal vessels; (9) diaphragm angle and/or diaphragm; (10) liver.
3. Extended total pancreatectomy
Standard total pancreatectomy is performed to combine one or more of the following organs: (1) distal stomach beyond the pylorus or more than half; (2) colon and/or colonic mesentery with vascularized transverse colonic mesentery (vessels mainly include: ileocolic, right colonic, mesocolic or left colonic vessels); (3) small intestine distal to the beginning of the jejunum; (4) portal vein, superior mesenteric vein and/or inferior mesenteric vein; ( (5) hepatic artery, celiac trunk, and/or superior mesenteric artery; (6) inferior vena cava; (7) right and/or left adrenal gland; (8) kidney and/or its vessels; (9) diaphragm angle and/or diaphragm; and (10) liver.
The consensus particularly emphasizes that (1) whether standard or extended resection is performed, it is necessary to ensure that the pancreatic margins are negative, and extended resection is still necessary to ensure complete removal of the tumor visible to the naked eye. If the tumor is free of distant metastases and negative margins can be obtained, and if the preserved or reconstructed vessels can maintain normal blood supply to the remaining organs, then we consider the tumor to be completely resected. (2) The concept of “combined pancreatic and multivisceral resection” is discarded because standard pancreatic resection is itself a multivisceral resection procedure. (3) For standard pancreatectomy combined with resection of a distant metastatic organ or second primary tumor, it should not be called “extended pancreatectomy” and the term “pancreatectomy combined with resection of a non-adjacent organ” should be used.
The naming of pancreatic surgical lymph nodes
The nomenclature of pancreatic surgical lymph nodes was mainly based on the Union International Contre le Cancer (UICC) standards and the nomenclature rules of the Japanese Pancreatic Society. However, based on several prospective studies and the specific nature of each classification standard, the participants unanimously adopted and recommended the classification standard of the Japanese Pancreatic Society, which was revised in 2003.
IV. Standard lymph node dissection for pancreatic cancer
In resectable pancreatic cancer, lymph node metastasis directly determines the patient’s prognosis. However, there is no clear definition of the standard lymph node dissection scope internationally. Therefore, another important purpose of this meeting is to develop an expert consensus on the scope of lymph node dissection for pancreatic resection.
1. Scope of lymph node dissection for pancreaticoduodenectomy
In the standard pancreaticoduodenectomy, the standard lymph node dissection should first reach No.13 and No.17 lymph nodes, because these two groups of lymph nodes are enclosed in the groove formed by the pancreas and duodenum, therefore, they are easy to be removed together with the specimen; for the lymph nodes in the right area of the superior mesenteric artery, it is recommended to routinely perform lymph node dissection in this area because of its high positive rate and tumor recurrence rate. For the lymph nodes around the superior mesenteric artery, the results of related studies suggest that complete resection does not bring benefits to patients and is very likely to cause postoperative complications such as diarrhea and weight loss. Therefore, the standard lymph node clearance only includes No.14a and No.14p lymph nodes on the right side of the superior mesenteric artery; it is also controversial how to clear the lymph nodes in the hepatoduodenal ligament, which mainly includes No.12 proximally to No.5 and 6 relatively distally, and the specific clearance mainly includes No.5, 6, 8a, 12b and 12c. The majority of scholars oppose the routine clearance of No.8p lymph nodes, but some suggest that the lymph node clearance should reach the level of the right hepatic artery; other studies have shown that the clearance of the pars splenic artery and the pars gastric artery lymph nodes in pancreaticoduodenectomy is not beneficial to improve the prognosis of patients; as to whether to clear No.16b1 lymph nodes, although some scholars have included No.16b1 lymph nodes in their resection plane, combining with the literature and other studies, it is believed that The lymph nodes of No.16b1 were included in the plane of lymph node dissection by some scholars.
In conclusion, the ISGPS recommends that the standard lymph node dissection includes: No.5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a right, 14b right, 17a and 17b lymph nodes.
2. Distal pancreatectomy
The lymph node clearance for distal pancreatectomy has been controversial because of the few studies on lymph node clearance for distal pancreatectomy, and the standard proposed by the Veneto Liberty Conference in Italy in 1999 has been used until now, and the specific lymph nodes to be cleared include No.9, 10, 11 and 18. In this meeting, scholars mainly expressed their opinions on whether to sweep No.9 lymph nodes, and some scholars advocated sweeping this group of lymph nodes for pancreatic body cancer immediately adjacent to the abdominal trunk, while other scholars expressed their opposition, so there was no consensus on No.9 lymph nodes in this meeting.
The consensus recommendation is that the standard lymph node dissection for distal pancreatectomy includes No. 10, 11 and 18 lymph nodes. When the tumor is confined to the body of the pancreas, No. 9 lymph node clearance can be considered. At the same time, in order to ensure the thoroughness of tumor resection and lymph node dissection, it is recommended to remove the spleen together (Figure 3).
3. About intraoperative lymph node frozen pathological section examination
The meeting discussed the issues related to intraoperative lymph node frozen section examination of pancreatic resection, and the consensus also elaborated on this issue: (1) preoperative imaging is actively performed, and if necessary, puncture biopsy is performed, and if metastases are found in lymph nodes outside the standard clearance range, then surgical exploration is not recommended; (2) during surgery, if suspicious lymph nodes outside the standard clearance range are found, they need to be removed and performed intraoperatively. (3) For tumors in the head of the pancreas, if intraoperative metastasis is found in lymph nodes outside the standard clearance area, the lymph nodes to the left of the superior mesenteric artery, the mesenteric root or around the abdominal trunk should be explored, and finally, the area of lymph nodes beyond the standard cut edge or even metastatic lymph nodes should be resected; (4) When intraoperative metastasis is found in No.16 lymph nodes, most scholars advocate continued surgical resection in an effort to achieve (4) When intraoperative metastasis is found in No.16 lymph nodes, most scholars advocate continuing surgical resection to achieve the ideal treatment goal. However, the decision to continue or discontinue surgery needs to take into account the relevant factors affecting the patient’s prognosis, such as underlying disease, age, vascular involvement and preoperative serum CA19-9 level.
4. Tumor stage and lymph node metastasis
Lymph node metastasis is crucial to determine the patient’s prognosis and to obtain accurate pathological diagnosis, and the standard lymph node dissection is of certain significance to determine the tumor stage and to select the appropriate multidisciplinary comprehensive treatment. In particular, at least 12~15 lymph nodes should be removed intraoperatively to ensure that the pathologist can obtain accurate lymph node metastasis staging. The lymph node metastasis ratio (LNR) is an important factor to judge the prognosis of patients, the higher the ratio, the worse the patient’s prognosis, and when the LNR>0.2, it can be considered as an independent factor affecting the prognosis. Of course, the more lymph nodes are cleared, the smaller the error in determining the stage of lymph node metastasis.
The consensus recommendation is that a standard lymph node dissection requires a minimum of 15 lymph nodes to provide the pathologist with an accurate determination of tumor staging; at the same time, a complete pathology report should include the total number of lymph nodes dissected and the LNR ratio. A total of <15 lymph nodes may be accepted.
V. Choice between standard and extended resection
The clinical indications for standard resection include: (1) no distant metastasis; (2) no SMV and portal vein surrounded by tumor tissue, deformation, tumor thrombosis or imaging evidence of vein encapsulation by tumor tissue; (3) the tumor does not surround the SMA by more than 180?mm in the circumference of the vessel itself; (4) clear fat layer around the abdominal trunk, hepatic artery and SMA. The clinical indications for extended resection are summarized as follows: (1) the tumor involves the celiac trunk, hepatic artery or SMA, and there are suitable vessels proximal and distal to the involved artery for safe resection and reconstruction; (2) the tumor tissue wraps around the SMV or portal vein, or small segmental vein occlusion due to tumor tissue wrapping or cancer embolism, requiring combined vascular resection or reconstruction; (3) the tumor invades the transverse colon or mesenteric root, requiring (3) the tumor invades the transverse colon or mesenteric root and requires combined partial colectomy; (4) the tumor involves the ipsilateral adrenal gland.
Compared with standard pancreatectomy, the disadvantages of extended pancreatectomy are [16-23]: (1) longer operation time, increased bleeding and blood transfusion, and longer ICU stay and overall hospital stay. (2) Significantly higher postoperative complication rates. (3) Although the overall perioperative morbidity and mortality rates were close to those of standard resection, the incidence of complications and morbidity and mortality rates due to resection of different organs varied widely. If one or more of the celiac trunk, common hepatic artery, and/or superior mesenteric artery are removed, postoperative complication rates and morbidity and mortality rates are significantly increased. (4) Extended resection does not prolong patient survival. Based on evidence-based medicine, the ISGPS does not recommend extended pancreatectomy. However, ISGPS still encourages specialized research centers to select patients for enlarged resection strictly according to the criteria and carefully. The efficacy of this procedure and its guiding significance will be reasonably evaluated through the observation and follow-up of its long-term results, including the complication rate, morbidity and mortality rate, and even the impact on quality of life.
Based on the study of Pedrazzoli et al. and the views of the participants, the consensus also does not advocate extended lymph node dissection. There is no consensus on whether to routinely dissect the No. 16b1 lymph node, No. 8p lymph node, and posterior abdominal aorta lymph nodes [28-29]. However, lymph nodes outside the standard clearance area can be considered for resection if they happen to be located within the tumor resection plane; lymph nodes located to the left of the superior mesenteric artery or around the abdominal trunk are considered to be lymph nodes with distant metastases because they fall outside the standard pancreaticoduodenal resection area. Some scholars have attempted to clear the lymph nodes with metastases adjacent to the abdominal aorta after assessing the patient’s basic condition. For patients with metastatic lymph nodes adjacent to the abdominal aorta, either resection or bypass surgery is a reasonable treatment.
Although R0 resection is considered the most effective weapon to improve the prognosis of pancreatic cancer, surgical treatment alone still has obvious shortcomings. Combining with postoperative radiotherapy and chemotherapy and other comprehensive treatment modalities can enable patients to obtain a longer survival period. We should clearly understand that standard lymph node dissection is only an integral part of the overall treatment process.
VI. Conclusion
The ISGPS proposes this consensus so that surgeons can have rules to follow when facing problems related to surgical resection of pancreatic cancer, and to a certain extent, it avoids the over and under of the scope of surgical resection and lymph node dissection, and it is highly practical, leading and operable. It is a practical, leading and operational approach that integrates several other factors that affect the patient’s prognosis and selects the best and reasonable treatment modality with a view to obtaining a longer survival period. This consensus provides a good theoretical basis for more high-level international studies and multicenter communication and collaboration in the future; admittedly, its scientific validity and effectiveness need to be confirmed by more clinical practice, as well as continuous development and improvement.