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Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

Yang, Yinmoa; Bai, Xuelib; Bian, Dapengc; Cai, Shouwangd; Chen, Rufue; Cao, Fengf; Dai, Menghuag; Fang, Chihuah; Fu, Deliangi; Ge, Chunlinj; Guo, Xiaochaok; Hao, Chunyil; Hao, Jihuim; Huang, Heguangn; Jian, Zhixiango; Jin, Gangp; Li, Feif; Li, Haiminq; Li, Shengpingr; Li, Weiqins; Li, Yixiongt; Li, Hongzhenu; Liang, Tingbob; Liu, Xubaov; Lou, Wenhuiw; Miao, Yix; Mou, Yipingy; Peng, Chenghongz; Qin, Renyiaa; Shao, Chenghaobb; Sun, Beicc; Tan, Guangdd; Tian, Xiaodonga; Wang, Huaizhiee; Wang, Leiff; Wang, Weigg; Wang, Weilinhh; Wei, Junminii; Wu, Heshuijj; Wu, Wenmingg; Wu, Zhengkk; Xu, Jingyongii; Yan, Changqingll; Yin, Xiaoyumm; Yu, Xianjungg; Yuan, Chunhuinn; Zhang, Taipinggg; Zhang, Jixinoo; Zhou, Junpp; Zhao, Yupeig,∗; on behalf of the Chinese Pancreatic Surgery Association

Author Information
doi: 10.1097/JP9.0000000000000072
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Abstract

Introduction

The incidence of pancreatic cancer has been rising continuously worldwide. According to the 2021 Cancer Statistics, in the United States, pancreatic cancer was ranked 10th with respect to the number of new cancer cases in men; 9th, number of new cancer cases in women; and 4th, cancer mortality.[1] According to the 2017 cancer statistics reported by China's National Cancer Center, pancreatic cancer was ranked 7th in men and 11th in women with respect to the incidence of malignant tumors and was ranked 6th with respect to malignant tumor mortality in China.[2] As one of the gastrointestinal tumors with the poorest prognoses, its clinical diagnosis and treatment remain a challenge; pancreatic cancer is clinically characterized by difficulties in early diagnosis and a low success rate in surgical dissection. Therefore, the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China (2014 version) were revised by Chinese Pancreatic Association, Chinese Medical Association's Chinese Society of Surgery to standardize the clinical diagnosis and treatment of pancreatic cancer in China, improve the ability to diagnose and surgically treat this disease, and discuss developments in diagnosis and treatment in recent years. Herein, after reviewing recently published evidence-based and problem-oriented literature, the researchers comment on popular topics regarding the diagnosis and treatment of pancreatic cancer and propose recommendations based on their clinical experience. These guidelines are expected to act as a reference and provide guidance for the development of strategies for clinical diagnosis and treatment and for the selection of appropriate treatment regimens.

The quality of the evidence and strength of the recommendations were graded using the Grades of Recommendation, Assessment, Development, and Evaluation system. The quality of evidence was classified as high, moderate, or low. The strength of the recommendations was ranked as either strong or weak.[3] The current guidelines are only applicable for malignancies derived from the pancreatic ductal epithelium, that is, pancreatic cancer.

The diagnosis and treatment of pancreatic cancer should be performed by a multidisciplinary team composed of physicians from specialties such as pancreatic surgery, radiology, endoscopy, pathology, oncology, intervention, radiotherapy, and others. Individualized diagnosis and treatment regimens should be formulated to achieve the optimal therapeutic effect according to the patient's physical status, clinical symptoms, tumor site, and tumor staging.

Diagnosis of pancreatic cancer

Clinical manifestations and high-risk factors

Depending on the involved organs and the tumor's location, size, and severity, the clinical manifestations of pancreatic cancer include upper abdominal or back pain, nausea, abdominal distension, jaundice, new-onset diabetes mellitus, weight loss, and stool changes, as well as occasional acute pancreatitis. The above symptoms are not specific, and some patients have no clinical symptoms. Pancreatic cancer is occasionally found during physical examination.

The risk factors for pancreatic cancer include obesity, type 2 diabetes mellitus, and smoking. Moreover, 5% to 10% of pancreatic cancer patients have genetic susceptibility factors (Table 1).[4]

Table 1 - Pancreatic cancer susceptibility genes
Syndrome Gene Estimated risk of pancreatic cancer Risk compared with that in the general population
Peutz-Jeghers syndrome STK11 11–36%(∼65–70 years old) 132
Familial pancreatitis PRSS1,SPINK1, CFTR 40–53% (∼70–75 years old) 26–87
Melanoma-pancreatic cancer syndrome CDKN2A 14–17% (∼70 years old) 20–47
Lynch syndrome MLH1, MSH2(MSH6) 4% (∼70 years old) 9–11
Hereditary breast and ovarian cancer syndrome BRCA1, BRCA2 1.4–1.5% (female, ∼70 years old); 2.1–4.1% (male, ∼70 years old) 2.4–6

According to statistics from the China Pancreas Data Center (CPDC), among more than 10,000 pancreatic cancer patients who underwent surgical treatment in high-volume pancreatic centers in China over the past 5 years, patients from East China accounted for the highest proportion. Among them, 60% of patients were male, 53% were aged 60 to 74 years, 27% had a history of smoking, 17% had a history of alcohol consumption, and only 1% had a family history of pancreatic cancer.

Recommendation 1: The clinical manifestations of pancreatic cancer are not specific. Screening should be carried out regularly for people with a genetic predisposition to pancreatic cancer.

Quality of evidence: High

Strength of recommendation: Strong

Significance of serum tumor markers in the diagnosis of pancreatic cancer and efficacy evaluation

Serum carbohydrate antigen 19-9 (CA19-9) is the most commonly used tumor marker for pancreatic cancer diagnosis. Its sensitivity and specificity have been found to be 79% to 81% and 82% to 90%, respectively. Because CA19-9 levels are also abnormally elevated in patients with biliary obstruction or infection, the baseline CA19-9 level should be determined only after the resolution of jaundice or bile duct infection. Serum CA19-9 levels may reflect the tumor burden or predict micrometastases to some extent.[5] In addition to its diagnostic significance, CA19-9 is also helpful for evaluating the prognosis and curative effect of a treatment.[6] Although an increase in serum CA19-9 levels after the resection of pancreatic cancer may indicate recurrence or metastasis, this should be further confirmed by radiological evidence.

Approximately 10% of pancreatic cancer patients have a Lewis-negative blood group phenotype, and CA19-9 is not expressed in such a population. Therefore, other tumor markers are needed to aid in diagnosis. CEA is one such marker, with a diagnostic specificity similar to that of CA19-9 but a sensitivity of only 44.2%. Likewise, elevated CA125 levels are associated with early postoperative distant metastasis from pancreatic cancer, predicting the possibility of tumor metastasis and the tumor burden to a certain extent. Particularly, in pancreatic cancer patients without elevated CA19-9 levels, CA125 has certain prognostic value.[7,8] CA50, CA242, CA724, and other tumor markers are also commonly used in clinical settings. The combined evaluation of CA50, CA242, and CA724 can help improve the diagnostic sensitivity and specificity for pancreatic cancer, but this should be further confirmed by high-quality evidence.

In addition to serum tumor markers, other biological target-based liquid biopsy technologies involving the detection of circulating tumor DNA, circulating tumor cells, and exosomes have shown potential for application in the diagnosis of pancreatic cancer and the evaluation of treatment efficacy. Samples obtained via liquid biopsy are expected to be important for early diagnosis, prognosis evaluation, postoperative recurrence/metastasis monitoring, and evaluation of the curative effect, but their popularization and application require verification by high-quality clinical studies.

Recommendation 2: Dynamic monitoring of CA19-9 and other serum tumor markers is helpful for diagnosis, prognosis evaluation, postoperative recurrence/metastasis monitoring, and curative effect evaluation in the context of pancreatic cancer.

Quality of evidence: High

Strength of recommendation: Strong

Application of imaging techniques in the diagnosis and treatment of pancreatic cancer

Imaging examination is the most important basis for the clinical diagnosis of pancreatic cancer. It is important before (staging and resectability evaluation), during (evaluation of the efficacy of neoadjuvant or conversion therapy), and after treatment (curative effect evaluation, postoperative monitoring, and follow-up). For patients scheduled to undergo biliary stenting for jaundice relief, imaging investigations should be completed before stent implantation to avoid interference from the stent during imaging of the tumor and its surrounding anatomical structures.

The commonly used imaging methods are multiphase contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Multiphase contrast-enhanced CT is the first choice for the diagnosis of pancreatic cancer. CT reconstruction with thin slices can clearly display the size, location, density, and blood supply of a pancreatic tumor; can be used to judge the relationship between the tumor, surrounding vessels, and adjacent organs; and can be used to evaluate tumor resectability and the efficacy of neoadjuvant therapy. MRI is also advantageous for the diagnosis of liver metastases when combined with the administration of liver-specific contrast agents and diffusion-weighted imaging. For pancreatic cancer patients with atypical imaging manifestations (such as those with a tumor density similar to that of the normal pancreatic parenchyma, those with high-density cystic lesions, or those with secondary pancreatitis or an inflammatory mass), multi-parameter MRI is helpful for differential diagnosis and can be used as an important supplement to CT.[9] Magnetic resonance cholangiopancreatography combined with dynamic contrast-enhanced thin-slice MRI is helpful for differentiating between cystic and solid lesions of the pancreas and further clarifying the dilatation and involvement of the pancreatic duct.

Positron emission tomography (PET)/CT or PET/MRI can supplement CT or MRI to reveal the metabolic activity and burden of a pancreatic tumor, detect extrapancreatic metastasis, and evaluate the whole-body tumor burden. PET/CT is recommended for evaluating the whole-body condition in patients with a high risk of extrapancreatic metastasis, such as in cases of a borderline resectable tumor, obviously elevated CA19-9 levels, and a large primary tumor or regional lymph node metastasis, or if there is a need to distinguish benign lesions from malignant lesions.

Recommendation 3: Multiphase contrast-enhanced CT with thin slices (≤1 mm) is the first choice for the preoperative diagnosis and staging of pancreatic cancer. For some patients with suspected pancreatic cancer, particularly for those with suspected liver metastasis, dynamic contrast-enhanced MRI is recommended for further evaluation.

Quality of evidence: High

Strength of recommendation: Strong

Recommendation 4: For patients who intend to undergo biliary stenting for jaundice relief, imaging examination should be completed before stent implantation.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 5: As a supplement to CT or MRI, PET/CT is suitable for patients with a high risk of extrapancreatic metastasis or in cases in which the nature of the pancreatic tumor needs to be identified.

Quality of evidence: Moderate

Strength of recommendation: Weak

Application of endoscopic ultrasonography in the preoperative diagnosis of pancreatic cancer

Endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration can not only help determine the size of the tumor (T stage) and metastasis to the lymph nodes around the pancreas (N stage) but can also be used to obtain histopathological specimens for pathological diagnosis. The sensitivity and specificity of EUS were 72% and 90%, respectively, in the diagnosis of T1–2 pancreatic cancer and 90% and 72%, respectively, in the diagnosis of T3–4 pancreatic cancer. Furthermore, EUS is superior to CT and MRI in determining the involvement of the superior mesenteric and portal veins.[10] In recent years, the measurement of strain ratios based on EUS has been reported to help in determining the content of the pancreatic cancer stroma and guiding clinical drug selection.[11]

EUS is an invasive procedure, and its accuracy for T/N staging and identifying pathological diagnosis is greatly affected by the operator's skills and experience. In the clinic, EUS is mainly used to guide puncture to obtain tissue samples. For patients with a clear diagnosis and clear surgical indications, routine EUS before surgery is not necessary.

Recommendation 6: EUS has certain advantages for tumor staging, but its accuracy for staging is greatly affected by the operator's skills and experience. In the clinic, EUS is mostly used to guide puncture to obtain a tissue sample. It is not recommended as a routine method for staging and the diagnosis of pancreatic cancer.

Quality of evidence: Moderate

Strength of recommendation: Weak

Application of three-dimensional visualization in the diagnosis and treatment of pancreatic cancer

Three-dimensional (3D) visualization is a tool used to display the 3D anatomical structure and morphological characteristics of a pancreatic tumor and its surrounding ducts. The shape and spatial distribution of the pancreas, tumor, blood vessels, biliary tract, and other targets are described by analyzing, fusing, processing, segmenting, and rendering CT or MRI data using computer image processing technology. This can visually display the targets accurately and quickly, providing references for accurate preoperative diagnosis, development of individualized surgical regimens, and surgical approach selection. The location, shape, and invasion of a pancreatic tumor; the route of and variation in important surrounding blood vessels; and the 3D spatial relationship between the pancreatic tumor and surrounding blood vessels can be clearly displayed on 3D models. This is helpful for preoperative resectability assessment and surgical strategy formulation.[12]

Recommendation 7: For patients with pancreatic cancer involving the surrounding blood vessels, 3D visualization technology is helpful for preoperative resectability assessment and surgical strategy selection.

Quality of evidence: Moderate

Strength of recommendation: Weak

Pancreatic tumor staging and resectability assessment

Details of pancreatic tumor staging are shown in Tables 2 and 3.

Table 2 - Tumor-node-metastasis classification for pancreatic cancer (the 8th edition of the American Joint Commission on Cancer (AJCC) Staging System)
Abbreviation Meaning
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ (including pancreatic intraepithelial neoplasia 3)
T1 Pancreatic cancer measuring ≤2 cm in the greatest dimension
T1a Pancreatic cancer measuring ≤0.5 cm in the greatest dimension
T1b Pancreatic cancer measuring >0.5 cm and ≤1 cm in the greatest dimension
T1c Pancreatic cancer measuring >1 cm and ≤2 cm in the greatest dimension
T2 Pancreatic cancer measuring >2 cm and ≤4 cm in the greatest dimension
T3 Pancreatic cancer measuring >4 cm in the greatest dimension
T4 Pancreatic cancer invading the celiac trunk, superior mesenteric artery, and/or common hepatic artery
Nx Regional lymph node(s) cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis to 1–3 regional lymph nodes
N2 Metastasis in ≥4 regional lymph nodes
M0 No distant metastasis
M1 Distant metastasis
M = distant metastasis, N = regional lymph node, T = primary tumor.

Table 3 - Pancreatic cancer stage (the 8th edition of the AJCC Staging System)
Staging features

Stage Tumor Node Metastasis
0 Tis N0 M0
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1–3 N1 M0
III T4Any T Any NN2 M0M0
IV Any T Any N M1

Based on the relationship between the tumor and its important surrounding blood vessels and distant metastases, tumor resectability is assessed, and the tumor is then classified as follows: resectable, borderline resectable, and unresectable (Table 4).

Table 4 - Imaging assessment of pancreatic cancer resectability
State Arteries Veins
Resectable If the tumor(s) does not invade the celiac trunk, superior mesenteric artery, or common hepatic artery. If the tumor(s) does not invade the superior mesenteric vein or portal vein, or if the tumor does invade these vessels but the invasion range does not exceed 180 degrees, and the vein contour is regular.
Borderline resectable Pancreatic head and neck tumor(s):If the tumor(s) invades the common hepatic artery but not the celiac trunk or the origin of the left and right hepatic arteries; if the tumor(s) invades the superior mesenteric artery, but the invasion range does not exceed 180 degrees, and there are arterial anatomical variations, such as those in the accessory right hepatic artery, alternative right hepatic artery, and alternative common hepatic artery; the invasion range should be identified as this may affect surgical decision-making. Pancreatic head and neck tumor(s):The tumor(s) invades the inferior vena cava; if the tumor(s) invades the superior mesenteric vein with an invasion range of over 180 degrees or the tumor(s) invades the superior mesenteric vein with an invasion range of less than 180 degrees, but the vein contour is irregular or vein thrombosis exists, the tumor(s) can be resected, and vein reconstruction is feasible.
Pancreatic body/tail tumors:The tumor(s) invades the celiac trunk with an invasion range of less than 180 degrees, with no invasion into the abdominal aorta or gastroduodenal artery (some scholars consider this situation to represent the stage of local progression). Pancreatic body/tail tumors:If the tumor(s) invades the entrance of the splenic and portal veins or the tumor(s) invades the left side of the portal vein with an invasion range of 180 degrees or less and the portal vein contour is irregular, then the involved vessels can be completely resected, and proximal and distant vessels can be reconstructed. The tumor(s) can be resected if it invades the inferior vena cava.
Unresectable Local progressive stage Pancreatic head and neck tumor(s):The tumor(s) invades the superior mesenteric artery with an invasion range of over 180 degrees; the tumor(s) invades the celiac trunk with an invasion range of over 180 degrees. Pancreatic head and neck tumor(s):The superior mesenteric vein or portal vein cannot be resected because of tumor invasion or embolism (tumor thrombus or thrombus). The tumor(s) extends to the distal jejunal drainage branch of the superior mesenteric vein.
Pancreatic body/tail tumors:The tumor(s) invades the superior mesenteric artery or celiac trunk with an invasion range of more than 180 degrees; the celiac trunk and abdominal aorta are involved. Pancreatic body/tail tumors:The superior mesenteric vein or portal vein invaded by the tumor(s) cannot be resected or reconstructed after invasion or embolization (tumor thrombus or thrombus).
Complicated by distant metastasis Distant metastasis (including lymph node metastasis beyond the scope of resection). Distant metastasis (including lymph node metastasis beyond the scope of resection).

The above criteria are based on the results of CT, MRI, and other imaging examinations that assess the resectability of pancreatic cancer only at the regional anatomical level. Other biological criteria such as tumor markers, PET/CT findings, and the general situation of the patient should be used for comprehensive assessment.

Recommendation 8: Involvement of a multidisciplinary team (MDT) is recommended for the staging and resectability assessment of pancreatic cancer. Anatomically, the resectability of pancreatic cancer is assessed from the perspectives of whether the main surrounding blood vessels are involved, whether distant metastasis exists, and whether R0 resection can be achieved.

Quality of evidence: High

Strength of recommendation: Strong

Application of neoadjuvant therapy in the treatment of pancreatic cancer

Application of neoadjuvant therapy in the treatment of resectable pancreatic cancer

Whether patients with resectable pancreatic cancer should receive neoadjuvant therapy remains controversial. Although there is evidence that neoadjuvant therapy is promising for increasing the R0 resection rate and lowering the positive rate of lymph nodes in patients with resectable pancreatic cancer, the sizes of study samples are generally limited, the quality of evidence is not high, and obvious heterogeneity exists among studies.[13–15] One previous study[16] showed that in approximately 20% of patients with resectable pancreatic cancer, the disease progresses due to failure of neoadjuvant treatment, and the opportunity for surgical treatment is missed. Preoperative puncture biopsy for elucidating the pathological diagnosis and catheter drainage for jaundice reduction are both invasive operations that have potential risks of bleeding, cholangitis, pancreatic fistula, and tumor dissemination. Therefore, caution is necessary when administering neoadjuvant therapy to patients with resectable pancreatic cancer.

At present, the guidelines in China and other countries recommend neoadjuvant therapy in high-risk patients with a clear pathological diagnosis of resectable pancreatic cancer. The known risk factors of pancreatic cancer include abnormally increased CA19-9 levels, large tumor size, suspected regional lymph node metastasis, abnormal weight loss, and obvious pain. For patients with resectable pancreatic cancer who have these risk factors, neoadjuvant therapy should be administered after an MDT discussion based on the patient's willingness, physical status, and individual situation. At present, there are no consistent quantitative standards regarding the abovementioned risk factors for resectable pancreatic cancer; therefore, relevant clinical studies should be performed.[17]

There is no standardized neoadjuvant therapy for resectable pancreatic cancer. For patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, the modified FOLFIRINOX regimen or albumin-bound paclitaxel combined with gemcitabine and other drugs are recommended. The curative effect is evaluated after 2 to 4 weeks of treatment before surgery. A randomized controlled trial (RCT) in Japan (Prep-02/JSAP-05) revealed that preoperative treatment with gemcitabine combined with S-1 can greatly increase the overall survival of patients with resectable pancreatic cancer and can be used as an alternative treatment option.[15] During treatment, changes in tumor index trends and imaging assessment results should be closely monitored, severe adverse reactions should be treated, and nutritional support should be provided. For patients showing a poor response to neoadjuvant therapy, surgical intervention should be performed in time. If resection is impossible due to disease progression, the treatment principle for unresectable pancreatic cancer should be followed. There is a lack of high-quality evidence to support the use of radiotherapy in the neoadjuvant treatment of pancreatic cancer; therefore, radiotherapy can be applied only after situation-dependent evaluation.

Recommendation 9: Neoadjuvant therapy is not recommended as a routine treatment for all patients with resectable pancreatic cancer.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 10: For high-risk patients with resectable pancreatic cancer, neoadjuvant therapy is recommended; other relevant clinical studies are required.

Quality of evidence: Moderate

Strength of recommendation: Strong

Application of neoadjuvant therapy in the treatment of borderline resectable pancreatic cancer

Neoadjuvant therapy is recommended for patients with borderline resectable pancreatic cancer because direct resection is likely to result in R1 or R2 resection margins and limited improvement in prognosis. Neoadjuvant therapy has been shown to increase the R0 resection rate and improve both cancer-free survival and overall survival.[14,18] In addition, neoadjuvant therapy is helpful for evaluating the biological behavior of the tumor. If the disease progresses during neoadjuvant treatment, it is unlikely the patient will benefit from surgery because of aggressive biological tumor behavior. Therefore, neoadjuvant therapy is initially administered to patients with borderline resectable pancreatic cancer with an ECOG performance status of 0 to 1.

While the optimal neoadjuvant therapy has not yet been identified, available protocols include FOLFIRINOX, modified FOLFIRINOX, FOLFIRINOX combined with sequential chemoradiotherapy, albumin-bound paclitaxel combined with gemcitabine, and albumin-bound paclitaxel combined with sequential chemoradiotherapy. For patients with a BRCA1/2 or PALB2 mutation, platinum-based chemotherapy, platinum-based chemotherapy combined with sequential chemoradiotherapy, gemcitabine combined with cisplatin (2–6 cycles), or gemcitabine combined with sequential chemoradiotherapy are recommended. FOLFIRINOX and modified FOLFIRINOX have been shown to greatly increase the R0 resection rate in patients with borderline resectable pancreatic cancer and to prolong the median progression-free survival and overall survival. Nevertheless, these regimens have severe side effects and are poorly tolerated by patients. No significant differences in the increase in the R0 resection rate or prolongation of overall survival have been found between the albumin-bound paclitaxel combined with gemcitabine regimen and the FOLFIRINOX regimen.[19,20] Gemcitabine combined with S-1 is less toxic than other regimens and is also a feasible choice for the neoadjuvant treatment of borderline resectable pancreatic cancer. A phase II clinical study showed that gemcitabine combined with S-1 can effectively increase the R0 resection rate and prolong overall survival in this patient population.[21] However, there is currently no high-quality clinical study comparing the results of various neoadjuvant treatment regimens. It is suggested that individualized neoadjuvant treatment regimens should be developed through an MDT discussion. For patients with an ECOG performance status of 0 to 1, gemcitabine combined with S-1 is recommended to achieve high objective efficiency. For patients with a poor ECOG performance status, a gemcitabine or fluorouracil-based chemotherapy regimen can be considered. At present, there is no clear standard for the number of neoadjuvant therapy cycles; generally, 2 to 4 cycles are recommended. The efficacy of neoadjuvant therapy is assessed by the MDT according to changes in tumor size, tumor markers, clinical manifestations, and physical status before and after treatment. In patients with no disease progression after neoadjuvant therapy, surgical exploration should be performed even if imaging examination does not show significant down-regulation of tumor markers. Laparoscopic exploration is the first-choice procedure, and radical resection should be performed after ruling out distant metastasis.

Radiotherapy cannot be used as the single means of neoadjuvant therapy, and its role in the combination with neoadjuvant chemotherapy requires further confirmation by prospective studies.

Recommendation 11: Neoadjuvant therapy is helpful to increase the R0 resection rate in patients with borderline resectable pancreatic cancer and to improve prognosis. Neoadjuvant therapy is recommended for all patients with borderline resectable pancreatic cancer with good physical performance status.

Quality of evidence: High

Strength of recommendation: Strong

Evaluation of the efficacy of neoadjuvant therapy for pancreatic cancer

There is currently no ideal method to evaluate the efficacy of neoadjuvant therapy in patients with pancreatic cancer. The Response Evaluation Criteria in Solid Tumors (RECIST) is a conventional imaging-based standard used to intuitively evaluate the efficacy of neoadjuvant therapy for pancreatic cancer according to changes in the size of target lesions seen on CT or MRI before and after neoadjuvant therapy. This method enables standardized evaluation and had high operability. However, it cannot reflect biological characteristics such as tumor heterogeneity and activity, blood supply, and immune cell infiltration. Because the stroma is also rich in pancreatic cancer tissue, the tissue adjacent to the tumor will also become inflamed and fibrotic after neoadjuvant therapy. Even if neoadjuvant therapy is effective, there are often no significant changes in tumor size and the range of important blood vessels showing involvement. Therefore, it is difficult to use the RECIST to accurately evaluate the effect of neoadjuvant therapy and tumor resectability in pancreatic cancer. PET/CT has recently been shown to enable more accurate evaluation of the efficacy of neoadjuvant therapy than CT. Moreover, the change in uptake value after neoadjuvant therapy relative to that before treatment is also related to prognosis.[22] Taken together, accurate evaluation of the efficacy of neoadjuvant therapy for pancreatic cancer remains a challenge. In recent years, quantitative and functional imaging modalities, such as dual-energy CT-based iodine quantification, CT or magnetic resonance perfusion scanning, diffusion-weighted imaging, and PET/MRI, can be used as important supplements to traditional morphological evaluation.

Serum CA19-9 levels represent an independent predictor of prognosis after neoadjuvant therapy. Patients whose CA19-9 level decreases by more than 50% after neoadjuvant therapy have good prognoses, and those whose CA19-9 level returns to normal have the most obvious survival benefit.[20,23] For patients with borderline resectable pancreatic cancer receiving neoadjuvant therapy, surgical exploration should be actively performed if CA19-9 levels are stable or decrease and if no tumor progression is found on imaging.

Recommendation 12: Imaging examination is the leading method to evaluate the efficacy of neoadjuvant therapy in patients with pancreatic cancer, and it should be combined with PET/CT, tumor marker evaluation, and consideration of the patient's general condition.

Quality of evidence: Low

Strength of recommendation: Weak

Pathological evaluation of pancreatic cancer after neoadjuvant therapy

Pathological findings of surgical specimens after neoadjuvant therapy can be used to evaluate treatment efficacy and prognosis and to guide follow-up treatment. Studies have shown that patients with a complete or near complete response to neoadjuvant therapy, as shown by pathological examination, have better prognoses than those with an extensive residual tumor.

At present, tumor regression is mostly scored based on the extent of the residual tumor in resected pancreatic specimens after neoadjuvant therapy. The 4-point tumor regression grading system modified from the Ryan grading system for colorectal cancer by the College of American Pathologists, as shown in Table 5, is mostly used.[24] Since the stroma is rich in pancreatic cancer tissue and neoadjuvant therapy promotes fibrosis, the change in tumor size after neoadjuvant therapy is not a strong finding to accurately reflect the therapeutic efficacy. Tumor regression should be comprehensively evaluated based on the number of residual tumor cells quantified through the microscope.

Table 5 - Modified Ryan tumor regression grading system
Description Tumor regression score
No viable cancer cells (complete response) 0
Single cells or small clusters of cancer cells (near complete response) 1
Residual cancer cells with obvious tumor regression, but the number of residual cancer cells is greater than that of single cells or small clusters of cancer cells (partial response) 2
Extensive residual cancer cells without obvious tumor regression (poor response or no response) 3

After neoadjuvant therapy, the resected specimens should be dissected into large-sized sections, and the therapeutic effect should be objectively evaluated. In addition, a sufficient quantity of specimen should be obtained to accurately evaluate the number of residual tumor cells.

Recommendation 13: After neoadjuvant therapy for pancreatic cancer, tumor regression is scored based on the number of residual tumor cells in the resected pancreatic specimens, usually via a 4-point scoring system.

Quality of evidence: Moderate

Strength of recommendation: Strong

Surgical treatment of pancreatic cancer

Preoperative nutritional assessment and nutritional support in patients with pancreatic cancer

A previous study showed that the risk of malnutrition in patients with pancreatic cancer was 91.1%, which was higher than that in patients with other digestive system and non-pancreatic tumors.[25] A multicenter retrospective cohort study on patients undergoing pancreatoduodenectomy in China showed that preoperative nutritional support significantly reduced the incidence of postoperative pancreatic fistula in patients with a Nutrition Risk Screening 2002 (NRS2002) score of ≥5.[26] The NRS2002 is a widely used nutritional screening tool for adult inpatients both in China and worldwide. It is suggested that nutrition screening should be completed at least 10 days before surgery, and nutritional issues should be identified in time for their diagnosis and treatment. As NRS2002 score of ≥3 is an indication for the formulation of a nutritional diagnosis and treatment program. The basic nutritional condition should be evaluated via nutrition-related history-taking, dietary investigation, physical examination, and laboratory examination. Based on the findings of the basic nutritional evaluation, nutritional interventions including nutritional consultation; dietary guidance; and administration of an oral nutrition supplement (ONS), enteral nutrition (tube feeding), or parenteral nutrition, should be performed.

The indications for preoperative nutritional support include the following: (1) weight loss of more than 15% of the body weight within 6 months; (2) body mass index <18.5 kg/m2; (3) Subjective Global Assessment of Nutritional Status (SGA) grade C; (4) an NRS2002 score >5; and (5) albumin levels of <30 g/L and normal liver and kidney function. Body weight change and low body mass index are the most widely used indications.[27] For the majority of pancreatic cancer patients with nutritional risks, preoperative dietary guidance and ONS administration are sufficient for meeting nutritional needs. For patients with high nutritional risks or malnutrition, enteral nutrition, supplementary parenteral nutrition, or total parenteral nutrition can be administered if oral intake is not sufficient. Preoperative nutritional support should be continued for more than 7 days, the administered protein supplement dose should exceed 1.2g/kg per day, and energy should reach 70% of the physiological demand.[26,27]

Recommendation 14: The NRS2002 should be routinely used in preoperative nutritional risk screening and for the development of nutritional diagnosis and treatment schemes for patients with pancreatic cancer.

Quality of evidence: High

Strength of recommendation: Strong

Recommendation 15: Preoperative nutritional support such as dietary guidance, ONS administration, enteral nutrition, and parenteral nutrition can be provided according to nutritional status. Preoperative nutritional support should be applied for at least 7 days.

Quality of evidence: Moderate

Strength of recommendation: Strong

Preoperative biliary drainage

Preoperative biliary drainage (PBD) can alleviate obstructive jaundice before surgery; however, its effectiveness and necessity remain controversial. Conventional use of PBD is not recommended to reduce jaundice severity because it cannot decrease perioperative mortality and may increase the incidence of postoperative complications.[28] For patients with long-term biliary obstruction, obviously abnormal liver and kidney function, fever, and cholangitis, PBD is recommended to control infection, improve liver and kidney function, and improve perioperative safety. Biliary drainage should be performed before neoadjuvant therapy. There is no consensus on whether the severity of jaundice is a sign of PBD. Serum bilirubin levels of ≥250 μM (15 mg/dL) are mostly used as the criterion to define severe jaundice. Moreover, it remains controversial whether PBD should be performed before surgery, though the current recommendation is to make a comprehensive judgment according to the individual patient's condition. Drainage for jaundice reduction can improve the preoperative digestive and nutritional status. A plastic stent or self-expandable metal stent (SEMS) is used for PBD under endoscopy. Use of an SEMS is thought to lead to inflammation of and adhesion to surrounding tissues, which increase the difficulty of subsequent operations. Compared with an SEMS, a plastic stent costs less and is easier to remove; however, the incidence of stent obstruction and displacement during drainage after the use of a plastic stent is significantly greater than that after the use of an SEMS, and there is a greater need to replace a plastic stent because of its long indwelling time.[29] A fully covered SEMS (FCSEMS) has a longer patency time, greater ease of removal, and is more suitable for neoadjuvant therapy than a plastic stent and an uncovered SEMS. Therefore, for patients with a high possibility of undergoing pancreatic cancer resection and requiring a short indwelling time, a plastic stent is required. For patients who need a long indwelling time or who are scheduled to receive neoadjuvant therapy, an FCSEMS is preferred. If stent placement cannot be completed under the endoscope, endoscopic ultrasonography-guided biliary drainage (EUS-BD) is also feasible. When internal drainage conditions are not met, such as in cases of obstruction or reconstruction of the upper digestive tract, stenosis, and failure of stent placement, percutaneous transhepatic cholangial drainage (PTCD) is feasible. PTCD has little influence on the operation site and leads to complete drainage. Nevertheless, bile loss is not conducive to improvements in the preoperative digestive and nutritional status.

PTCD or endoscopic stent placement can lead to several complications. The former can lead to bleeding, bile leakage, infection, and peritoneal metastasis, while the latter can lead to acute pancreatitis and biliary tract infection. Such complications should be diagnosed and treated in a relatively large-scale research center.

Recommendation 16: PBD is suggested for pancreatic cancer-caused biliary obstruction complicated by cholangitis and delayed surgery due to other causes; endoscopic stent implantation is preferred.

Quality of evidence: Moderate

Strength of recommendation: Weak

Application of laparoscopic exploration in the diagnosis and treatment of pancreatic cancer

Palliative resection of pancreatic cancer fails to improve prognosis and can also delay systemic treatment, which is not conducive to the long-term survival of patients. In addition, early postoperative recurrence of pancreatic cancer is common, particularly in the liver and peritoneum, due in part to the existence of abdominal or liver micrometastases which are difficult to detect by preoperative imaging. Therefore, in high-risk patients with pancreatic cancer who are scheduled to undergo surgical resection, it is necessary to carefully perform a comprehensive laparoscopic exploration to locate any micrometastases and avoid palliative resection. It remains disputed whether preoperative laparoscopic exploration should be performed in patients with resectable pancreatic cancer without high-risk factors. However, laparoscopic exploration has low risk and many potential benefits; thus, preoperative laparoscopic exploration can be performed after comprehensive evaluation. Generally, the higher the tumor-node-metastasis stage, the higher is the positive rate of distant micrometastatic foci detected by laparoscopic exploration.

Laparoscopic exploration consists of examination of peritoneal (including the small intestine and sigmoid mesocolon) and liver micrometastases and exfoliative cytology. In one study, the positive rate of peritoneal micrometastatic foci of pancreatic cancer confirmed by laparoscopy was 11% to 56%.[30] There is evidence that the rate of positive peritoneal cytology findings in pancreatic cancer is approximately 10%, although whether positive peritoneal cytology indicates distant metastasis remains disputed. It has been found that pancreatic cancer patients with positive peritoneal cytology have poorer prognoses than those without.[31]

Recommendation 17: For high-risk patients with locally advanced and borderline resectable pancreatic cancer after neoadjuvant therapy, laparoscopic exploration before resection is recommended.

Quality of evidence: Moderate

Strength of recommendation: Strong

Laparoscopic and robot-assisted surgery for pancreatic cancer

To date, various laparoscopic and robot-assisted operations for pancreatic cancer have been performed. Surgical safety has improved greatly, and laparoscopic surgery and robot-assisted surgery have shown significant advancements. However, the therapeutic effect of laparoscopic and robot-assisted surgery for pancreatic cancer, in terms of oncology evaluation and surgical safety, remains greatly disputed.

Clinical studies have shown that there are no significant differences in the incidences of perioperative complications, such as pancreatic fistula, biliary fistula, delayed gastric emptying (DGE), bleeding, reoperation, and mortality, between laparoscopic pancreaticoduodenectomy (LPD) and open surgery.[32–35] Additionally, no significant differences have been reported in the number of removed lymph nodes and the R0 resection rate between the 2 surgeries. Moreover, postoperative hospital stay is shorter in patients undergoing LPD, and the procedure is beneficial with respect to early administration of adjuvant chemotherapy.[32–35] One meta-analysis showed that there was no significant difference in overall survival between LPD and open surgery and that recurrence-free survival after LPD was longer than that after open surgery.[36] These findings suggest that minimally invasive technology may confer survival benefits in patients with pancreatic cancer. However, special attention should be paid to the influence of the learning curve, the operator's experience, and the quality of surgery on the occurrence of perioperative complications, particularly with respect to how they affect the long-term prognosis of patients with pancreatic cancer. The laparoscopic technique to be applied for oncological evaluation should be verified by high-quality clinical studies.

Recommendation 18: Laparoscopic or robot-assisted radical pancreatectomy should be performed selectively by experienced surgeons. The laparoscopic technique to be used for oncological evaluation still requires verification by high-quality clinical studies.

Quality of evidence: Low

Strength of recommendation: Weak

Application of radical antegrade modular pancreatosplenectomy in the treatment of pancreatic body and tail cancer

Dissection of the pancreatic body and tail as well as the spleen is the standard operation for the treatment of pancreatic tail cancer. Under the standard scope for lymph node dissection, the lymph nodes around the splenic artery, near the lower edge of the pancreas, and near the splenic hilum should be removed. Under extended scope, lymph nodes near the common hepatic artery, in the celiac trunk, and on the left side of the superior mesenteric artery should be dissected. In 2003, Strasberg et al applied radical antegrade modular pancreatosplenectomy (RAMPS) in patients with pancreatic body and tail cancer. The procedure is divided into anterior and posterior RAMPS according to whether RAMPS is performed in combination with left adrenal gland resection. It results in the expansion of the retroperitoneal resection plane, improving R0 resection margins in the retroperitoneum and the dissection of vascular root lymph nodes, as shown in Figure 1.[37] The effect of RAMPS in terms of improvements in the long-term prognosis of pancreatic cancer remains unclear, but the theoretical rationality and perioperative safety of RAMPS help in increasing the R0 resection rate of pancreatic body and tail cancer, and RAMPS has increasingly been used in recent years.[38,39]

Figure 1
Figure 1:
Surgical schematic diagram for radical antegrade modular pancreatosplenectomy (RAMPS).

Recommendation 19: RAMPS can increase the R0 resection rate of pancreatic body and tail cancer. Its effect in terms of the improvement in long-term prognosis requires further evaluation.

Quality of evidence: Moderate

Strength of recommendation: Weak

Scope of lymph node dissection in the radical resection of pancreatic cancer

For the classification of lymph nodes affected by pancreatic cancer, the Japanese Pancreas Society classification has been used as the named standard in the literature from China and abroad (Fig. 2).

Figure 2
Figure 2:
The Japanese Pancreas Society classification of lymph nodes around the pancreas. For the classification of lymph nodes affected by pancreatic cancer, the Japanese Pancreas Society classification has been used as the named standard in China and abroad. 5: in the superior pylorus; 6: in the inferior pylorus; 7: beside the left gastric artery; 8a: in the anterior general hepatic artery; 8p: in the posterior general hepatic artery; 9: surrounding the abdominal artery; 10: splenic port; 11d: near the distal splenic artery; 11p: near the splenic artery; 12a: near the hepatic artery; 12b: near the common bile duct; 13a: at the upper edge of the dorsal pancreatic head; 12p: near the portal vein; 13b: at the inferior edge of the dorsal pancreatic head; 14d: in the distant superior mesenteric artery (between the beginning of the inferior pancreaticoduodenal artery and the beginning of the middle colic artery); 14p: near the proximal superior mesenteric artery (between the beginning of the superior mesenteric artery and the beginning of the inferior pancreaticoduodenal artery); 15: adjacent to the middle colic artery; 16: around the abdominal aorta; 17a: at the upper edge of the ventral pancreatic head; 17b: at the inferior edge of the ventral pancreatic head; and 18: at the inferior edge of the pancreas.

Standard scope for lymph node dissection in pancreaticoduodenectomy for pancreatic head cancer: lymph nodes in the superior and inferior pylorus (5, 6); near the anterior general hepatic artery (8); near the hepatoduodenal ligament, common hepatic duct, common bile duct, and cystic duct (12b); at the upper and lower edges of the dorsal pancreaticoduodenal region (13a-b); near the right superior mesenteric artery (14p-d); and at the anterior and inferior edges of the dorsal pancreaticoduodenal region (17a-b).

As shown in Figure 3, the uncinate process is completely removed, and the right side of the superior mesenteric artery (to 180°) is skeletonized. The aforementioned lymph nodes and specimens are dissected en bloc. Routine dissection of the lymph nodes behind the hepatic artery (8p) and beside the aorta (16b1) is not recommended. Dissection of the lymph nodes around the celiac artery trunk (8p), left gastric arteries (7), splenic arteries (11), and the superior mesenteric artery (14p-d) is also not recommended.

Figure 3
Figure 3:
Schematic of the standard scope for lymph node dissection in pancreatoduodenectomy for pancreatic head cancer. 5: in the superior pylorus; 6: in the inferior pylorus; 8a: in the anterior general hepatic artery; 12b: near the common bile duct; 13a: at the upper edge of the dorsal pancreatic head; 13b: at the inferior edge of the dorsal pancreatic head; 14d: in the distant superior mesenteric artery (between the beginning of the inferior pancreaticoduodenal artery and the beginning of the middle colic artery); 14p: near the proximal superior mesenteric artery (between the beginning of the superior mesenteric artery and the beginning of the inferior pancreaticoduodenal artery); 17a: at the upper edge of the ventral pancreatic head; 17b: at the inferior edge of the ventral pancreatic head; and 18: at the inferior edge of the pancreas.

Extended scope for lymph node dissection in pancreaticoduodenectomy for pancreatic head cancer: Based on the standard scope for lymph node dissection, lymph nodes near the retrohepatic inferior vena cava (8p), around the celiac trunk (9), around the proper hepatic artery (12a), near the posterior portal vein (12p), near the superior mesenteric artery (14p-d), and near the abdominal aorta (16a2, 16b1) should be dissected. The scope for the removal of lymph nodes, nerves, and connective tissue ranges from the hepatic hilum to the beginning of the inferior mesenteric artery and from the left edge of the abdominal aorta to the right renal hilum.

Standard scope for lymph node dissection in the resection of pancreatic body and tail cancer: Lymph nodes in the splenic hilum (10), around the splenic arteries (11), and at the inferior edge of the pancreas (18), as well as en bloc specimens are dissected. If the foci are located in the pancreatic body, lymph nodes around the abdominal arteries (9) should also be dissected (Fig. 4). For patients with a definite diagnosis of pancreatic body and tail cancer, resection of the pancreatic body and tail should be performed without preservation of the spleen.

Figure 4
Figure 4:
Schematic of the standard scope for lymph node dissection in pancreatic body and tail resection. 9: surrounding the abdominal artery; 10: splenic port; 11d: near the distal splenic artery; 11p: near the splenic artery; and 18: at the inferior edge of the pancreas.

Extended scope for lymph node dissection in the resection of pancreatic body and tail cancer: Based on the standard scope for lymph node dissection, lymph nodes around the common hepatic artery (8), celiac trunk (9), and superior mesenteric artery (14p-d), along with those near the abdominal aorta (16a2, 16b1), should be dissected.

Staerkle et al[40] performed a meta-analysis regarding the scope of lymph node dissection using seven RCT studies with clinical data from 843 patients with pancreatic and periampullary cancer. The results revealed that the values of operation time and intraoperative blood loss were significantly greater in patients undergoing lymph node dissection with an extended scope than in those undergoing lymph node dissection with standard scope, and there were no significant differences in perioperative mortality and overall survival between the two patient groups.[40] Hackert et al[41] performed a retrospective single-arm study and found that under systemic treatment, the dissection of nerve connective tissue within the triangle bordered by the celiac trunk, superior mesenteric artery, and portal vein improved the prognosis of patients with locally advanced pancreatic cancer. However, these results need to be verified by high-quality evidence. Furthermore, the dissection of lymph nodes within the standard scope is still recommended.

The correlation between prognosis and either the number of dissected lymph nodes or the ratio of positive lymph nodes to the total number of lymph nodes remains unclear. A sufficient number of lymph nodes in the specimen is helpful for accurate N staging and guiding subsequent adjuvant treatment. To emphasize the scope for intraoperative lymph node dissection, specimens should be evaluated by surgical and pathological departments, and >15 lymph nodes should be obtained.

Recommendation 20: Lymph node dissection within the standard scope is recommended for pancreatic cancer. More than 15 lymph nodes should be obtained for accurate lymph node staging.

Quality of evidence: Moderate

Strength of recommendation: Strong

Radical resection of pancreatic cancer combined with vessel resection

Pancreatic cancer often involves the superior mesenteric vein/portal vein and celiac trunk/hepatic artery system. To increase the radical resection rate, resection combined with reconstruction of the involved vessels is often required. For resectable pancreatic cancer with involvement of only the superior mesenteric vein/portal vein, pancreatoduodenectomy combined with resection of the respective vein is recommended based on systemic treatment. If R0 resection can be achieved, there is no significant difference in prognosis between patients undergoing radical resection of pancreatic cancer combined with vessel resection and those undergoing standard operations. However, the prognosis of patients undergoing radical resection of pancreatic cancer combined with vessel resection is significantly superior to that of patients undergoing palliative surgery. One meta-analysis showed that intraoperative blood loss, operation time, postoperative hospital stay, incidence of perioperative complications, and mortality within 30 days after surgery were significantly increased in patients undergoing radical resection of pancreatic cancer combined with vein resection, and the incidence rates of postoperative biliary fistula, DGE, reoperation, and abdominal bleeding in these patients were significantly higher than those in patients undergoing standard operations.[42] The main reasons for this are that in patients undergoing radical resection of pancreatic cancer combined with vein resection, the tumor volume and proportion of nerves invaded by the tumor are higher than those in patients undergoing standard operations, indicating that tumors in the former group may have aggressive biological behaviors.

There is no high-quality evidence supporting pancreatic cancer resection combined with artery resection and reconstruction. If safe artery resection and reconstruction are feasible and R0 resection is expected, surgical resection can be performed after MDT evaluation. For patients with pancreatic body/tail cancer involving the celiac trunk, systemic treatment combined with celiac trunk resection may improve prognosis. A retrospective study showed that the median survival duration in patients receiving neoadjuvant chemotherapy combined with artery resection was 23 months, which was longer than that in patients undergoing artery resection alone.[43] Before neoadjuvant chemotherapy combined with artery resection, the location and extent of tumor invasion, as well as the artery course and variation, should be evaluated. Digital subtraction angiography or CT angiography combined with 3D visualization is used for preoperative planning.

The incidence of complications and perioperative mortality after radical pancreatectomy with artery resection were higher than those after radical resection alone. Radical resection combined with artery resection has a limited radical effect, and thus, scholars should be more cautious with respect to surgical indications for radical pancreatectomy and artery resection than with those for vein resection. Radical resection of pancreatic cancer combined with superior mesenteric artery resection and reconstruction is not recommended.

Recommendation 21: For patients with the possibility of undergoing R0 resection, radical resection of pancreatic cancer combined with superior mesenteric vein/portal vein resection and reconstruction is recommended.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 22: For patients with pancreatic cancer involving the arteries, surgical indications should be evaluated according to the possibility of R0 resection, the regions involved, and whether reconstruction is required. Radical resection of pancreatic cancer combined with superior mesenteric artery resection is not recommended.

Quality of evidence: Low

Strength of recommendation: Weak

Palliative surgical treatment of unresectable pancreatic cancer

Although there is no consensus on the treatment of pancreatic head cancer with digestive tract obstruction, open or laparoscopic gastrojejunostomy and endoscopic stent placement are feasible options. Endoscopic stent placement is advantageous owing to its characteristics of minimal trauma, good tolerance, rapid postoperative recovery, low incidence of complications, and short hospital stay; however, a long stent indwelling duration has risks of displacement and occlusion, and the re-intervention rate is high.[44] Open or laparoscopic gastrojejunostomy is associated with a higher incidence of perioperative complications, leads to more reliable recovery of digestive tract function, and exhibits a lower re-intervention rate than endoscopic stent placement.

For patients with advanced pancreatic cancer complicated by digestive tract obstruction, gastrojejunostomy is recommended when prolonged survival (more than 3–6 months) is expected, the patient is in good general condition, and an enteral nutrition tube can be inserted during surgery for postoperative nutritional support. Endoscopic stent placement is recommended for patients with a short expected survival duration (less than 3 months) or the inability to tolerate the operation because of a poor general condition. No evidence exists that prophylactic gastrojejunostomy can benefit patients with pancreatic cancer without digestive tract obstruction, but the tumor cannot be radically removed during surgical exploration. In addition, prophylactic gastrojejunostomy can increase perioperative complications and delay systemic treatment. Therefore, prophylactic gastrojejunostomy is not recommended. For patients with unresectable pancreatic cancer with obstructive jaundice, endoscopic biliary stent placement is the first choice. Percutaneous transhepatic biliary drainage is the best option for patients with a failed stent placement or failed endoscopic biliary stent placement. Palliative choledochojejunostomy is only suitable for patients in whom jaundice cannot be reduced through endoscopy or percutaneous transhepatic biliary drainage because of technical difficulties or contraindications. Palliative choledochojejunostomy or double-bypass surgery (choledochojejunostomy + gastrojejunostomy) is recommended for patients in whom the tumor cannot be completely removed during surgical exploration or who underwent gastrojejunostomy due to digestive tract and biliary obstruction. After cholecystectomy, Roux-en-Y choledochojejunostomy is performed.

Recommendation 23: For advanced pancreatic cancer patients with digestive tract obstruction, gastrojejunostomy or endoscopic stent placement is generally recommended according to the patient's general condition.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 24: For patients with unresectable pancreatic cancer with biliary obstruction, endoscopic stent placement or PTCD is the first choice of treatment.

Quality of evidence: Moderate

Strength of recommendation: Strong

Conversion strategies for locally advanced pancreatic cancer

Locally advanced pancreatic cancer refers to a malignancy with extensive local invasion and surrounding vessel involvement but without distant metastasis. Together with pancreatic cancer with distant metastasis, locally advanced pancreatic cancer is an advanced unresectable cancer. In recent years, it has been estimated that 20% to 60% of locally advanced pancreatic cancers may be operated on through conversion therapy, with better prognosis in patients undergoing surgery than in patients not undergoing surgery.[45,46] Although no RCTs have been published to date, it is recommended that patients with locally advanced pancreatic cancer undergo conversion therapy.

Before conversion therapy, a cytological or pathological diagnosis should be established. For patients who cannot be diagnosed via repeated biopsy under the guidance of EUS, ultrasound, or CT, laparoscopic biopsy can be performed to establish the pathological diagnosis. There is no optimal conversion treatment. FOLFIRINOX, modified FOLFIRINOX, or albumin-bound paclitaxel combined with gemcitabine is generally used. For patients with BRCA1/2 or PALB2 mutations, platinum-based chemotherapy or platinum-based chemotherapy combined with sequential chemoradiotherapy is recommended. For patients with a poor physical performance status, gemcitabine or fluorouracil is recommended.

Pancreatectomy is recommended for patients with no tumor progression after conversion therapy, with good physical performance status on laparoscopic exploration, and in whom vessel resection and reconstruction are possible. Pancreatectomy is generally performed at 4 to 8 weeks after neoadjuvant therapy.

Recommendation 25: Some patients with locally advanced pancreatic cancer may have the surgical opportunity to improve their prognosis by conversion therapy. For patients with a good physical performance status, combined therapy is recommended. For patients with a poor physical performance status, gemcitabine- or fluorouracil-based chemoradiotherapy is recommended. A cytological or pathological diagnosis should be established before treatment.

Quality of evidence: Weak

Strength of recommendation: Strong

Treatment strategy for pancreatic cancer with oligometastasis

Oligometastasis refers to a type of metastasis in which the metastatic focus is limited to one organ (such as the liver) and can be completely removed together with the primary focus, as the tumor load is very low. In recent years, several retrospective studies have found that some highly selected pancreatic cancer patients with oligometastasis may benefit from surgery, and the prognosis is better in patients receiving systemic chemotherapy before pancreatectomy than in those undergoing pancreatectomy alone.[47] In addition to exhibiting a therapeutic effect, preoperative systemic therapy can also help evaluate the biological behavior of a tumor to screen for the patients who may potentially benefit. For patients with a good physical performance status, significantly reduced CA19-9 levels, stable or reduced metastatic lesions, and no new metastatic lesions after systemic chemotherapy, surgical treatment is recommended to radically resect the primary and metastatic foci. A previous study showed that poorly differentiated cancer, failure to achieve R0 resection, no preoperative systemic chemotherapy, and no postoperative chemotherapy independently affected the prognosis of patients with oligometastatic pancreatic cancer.[48] The survival of patients with pancreatic cancer complicated by lung metastasis is obviously longer than that of patients with pancreatic cancer complicated by other distant metastases; therefore, patients with pancreatic cancer complicated by oligometastasis to the lung can benefit from surgical treatment.[49]

There is no consensus on the treatment strategy for metachronous oligometastasis after radical resection of pancreatic cancer. Some retrospective studies have found that patients with oligometastasis to a single lung or the liver after radical resection of pancreatic cancer may still benefit from surgical treatment, and the prognosis improves with increasing intervals between metastasis resection and pancreatic surgery.[50,51] Mitsuka et al[51] found that patients with only liver metastasis after radical resection of pancreatic cancer and no new metastasis within 3 months of surgery had an average disease-free survival duration of 21 months after the removal of the liver metastatic foci, which was significantly longer than the average disease-free survival duration of 3 months in patients who did undergo the removal the liver metastases. Therefore, for patients with oligometastases after radical resection of pancreatic cancer, systemic treatment can be used to determine whether surgical treatment is feasible.

Based on systemic treatments, it is necessary to perform high-quality clinical trials, propose quantitative criteria for screening the pancreatic cancer population, and objectively evaluate the clinical significance of radical pancreatic cancer resection combined with resection of synchronous or metachronous oligometastatic foci.

Recommendation 26: For patients with pancreatic cancer combined with single-organ (such as the liver or lung) metastasis, systemic treatment is the first choice. Surgical treatment can be attempted for patients with a good physical performance status, obviously decreased CA19-9 levels, stable or reduced metastatic foci assessed by imaging, and no new metastatic foci in whom the achievement of radical resection of both the primary and metastatic lesions is expected.

Quality of evidence: Weak

Strength of recommendation: Weak

Popular topics related to the postoperative management of patients with pancreatic cancer

Intraoperative nutrition tube placement and postoperative nutrition support strategy for patients with pancreatic cancer

Intraoperative nutrition can be administered via a jejunostomy, nasojejunal tubes, and nasogastric tubes. Under accelerated rehabilitation strategies, routine placement of an enteral nutrition tube during the operation is not recommended; placement of an enteral nutrition tube is only recommended postoperatively, when necessary. Moreover, a nasojejunal tube is preferred. The indications for an indwelling feeding tube include the following: (1) preoperative malnutrition, (2) high risk of postoperative complications, and (3) secondary operation. Due to high preoperative nutritional risks and the high malnutrition incidence, postoperative nutritional support should be administered more actively to patients with pancreatic cancer than to patients without a tumor. The energy target can be set at 25 kcal/kg per day, and the protein target can be set at 1.5 g/kg per day. For patients with a good nutritional status before surgery, reaching the nutritional standard within 3 days after surgery is not required, and nutritional status can gradually recover to meet the demand within 4 to 7 days post-operation. If 50% of the nutritional demand cannot be met through the oral route by 7 days after surgery, enteral or parenteral nutritional interventions can be considered.[52] For patients at high nutritional risk in whom indwelling feeding tubes had been placed during surgery, enteral nutrition should be started as soon as possible postoperatively, and parenteral nutrition should be administered within 4 days after surgery according to nutritional status.

A previous study showed that for pancreatic cancer patients with postoperative pancreatic fistula (POPF), an individualized nutritional support strategy is recommended; patients with a stable grade A POPF, that is, a “biochemical leak,” can continue to eat; for patients with a grade B or C POPF, oral feeding does not increase the fistula healing time, but it results in a shorter hospital stay and costs less than enteral and parenteral nutrition.[53] For all patients with a grade C POPF and some patients with a grade B POPF, enteral nutrition or a combination of enteral and parenteral nutrition is the first choice of treatment due to poor tolerance of oral feeding. DGE after pancreatectomy is the most important indication to start nutritional support. For patients with grade A DGE, oral feeding can be resumed within 2 weeks after surgery, while grade B DGE and grade C DGE have a course longer than 2 weeks and need artificial nutritional support. It is suggested that parenteral nutrition should be administered first, and enteral nutrition should be administered through a nasojejunal tube if the nutritional condition does not improve after 7 days. The disease course of patients with DGE is generally long; thus, the nutritional needs of patients should be guaranteed according to the principles of nutritional support, and parenteral nutrition should be supplemented when necessary.[52]

Recommendation 27: The feeding tube can be retained during surgery for patients with preoperative malnutrition, a high risk of postoperative complications, and those who need secondary surgery; a nasojejunal tube is preferred.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 28: When postoperative complications such as POPF occur, an individualized nutritional support plan should be formulated. The enteral route is favored, and parenteral nutrition should be supplemented when necessary.

Quality of evidence: Moderate

Strength of recommendation: Strong

Application of somatostatin and its analogs in patients with pancreatic cancer after surgery

Although the ability of somatostatin and its analogues to reduce the overall incidence of pancreatic fistula is controversial, it is generally agreed that no significant reduction is found after pancreatoduodenectomy. For patients with a soft pancreas, a pancreatic duct diameter of <3 mm, body mass index ≥25 kg/m2, diabetes mellitus, and other high-risk factors for pancreatic fistula, postoperative application of somatostatin and its analogs may reduce the risk of clinical pancreatic fistula.[54] At present, the widely used models to predict the risk of POPF mainly include the fistula risk score (FRS) and alternative FRS (a-FRS). The former includes four predictors: pancreatic texture, intraoperative blood loss, pancreatic duct diameter, and pathological type; in contrast, the latter includes three predictors: pancreatic texture, body mass index, and pancreatic duct diameter. In addition, the experience of the operator and anastomosis quality are also important factors affecting the risk of POPF. The risk of pancreatic fistula should be assessed in all patients undergoing pancreatic surgery. For patients at high risk, somatostatin and its analogs can be used prophylactically after surgery. Somatostatin is recommended for use until 2 to 3 days after surgery, after which oral feeding is applied.

Recommendation 29: After the assessment of the risk of POPF, somatostatin and its analogs can be prophylactically used in high-risk patients.

Quality of evidence: Moderate

Strength of recommendation: Strong

Management of an abdominal drainage tube after pancreatic cancer surgery

With the popularization and application of accelerated rehabilitation strategies, abdominal drainage after pancreatic surgery has attracted great attention. One main consideration is whether an abdominal drainage tube should be routinely placed after surgery, while another is the optimal timing of drainage tube removal post-operation. Although there are many contradicting conclusions from RCTs with respect to the former concern, routine placement of an abdominal drainage tube after surgery is still recommended. Additionally, some scholars have evaluated the risk of pancreatic fistula according to FRS score. It was believed that there was no need to insert an abdominal drainage tube in patients at low or no risk for pancreatic fistula (FRS = 0–2); for patients at moderate to high risk for pancreatic fistula (FRS = 3–10), it was determined that the risk of pancreatic fistula be predicted according to the amylase concentration in drainage fluid on the first day after surgery. In patients with an amylase concentration of <5000 U/L on the first day after surgery, removal of the drainage tube on the third day after surgery was found to significantly decrease the incidence of clinical pancreatic fistula.[55] In recent years, many scholars have attempted to remove the abdominal drainage tube early after surgery, but the indications of extubation vary greatly among studies. Single-center RCTs in China have confirmed that in patients presenting with an amylase concentration of <5000 U/L on the first and third days after pancreatic cancer surgery and a drainage fluid volume of <300 mL/d within 3 days after surgery, extubation on the third day greatly decreased the incidence of grade 2 to 4 complications after pancreaticoduodenectomy.[56] In subsequent multicenter RCTs, it was confirmed that it was safe and feasible to remove the abdominal drainage tube on the 3rd day after pancreatoduodenectomy in patients who met the above indications. In the group in which the abdominal drainage tube was removed on the third day post-surgery, the incidence of postoperative complications was similar to that in the delayed extubation group, but the postoperative hospital stay was significantly shorter.

Recommendation 30: Routine intra-abdominal drainage tube placement is recommended after pancreatic cancer surgery.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 31: For patients with low-risk pancreatic fistulae and satisfactory anastomosis, the drainage tube can be removed early after determining the amylase concentration and volume of drainage fluid.

Quality of evidence: Moderate

Strength of recommendation: Weak

Adjuvant treatment for pancreatic cancer after surgery

Adjuvant chemotherapy is effective in preventing or delaying the recurrence of pancreatic cancer. Adjuvant chemotherapy should be used only if there is no contraindication after radical surgery. In the past, fluorouracil- or gemcitabine-based combination chemotherapy was recommended; for patients with poor physical performance, single-drug chemotherapy was also recommended. In recent years, phase III clinical studies have confirmed that compared with the traditional gemcitabine monotherapy regimen, oral S-1 monotherapy, gemcitabine plus capecitabine, modified FOLFIRINOX, and other regimens significantly prolonged the disease-free and overall survival durations of patients with resectable pancreatic cancer.[57–59] Results of the APACT study revealed that albumin-bound paclitaxel plus gemcitabine can greatly prolong the overall survival of patients with pancreatic cancer after radical pancreatectomy. Subgroup analysis revealed that patients with T3N1–2 disease benefit more than other patient groups, and therefore, albumin-bound paclitaxel plus gemcitabine can be used as an alternative adjuvant chemotherapy regimen.[60] Postoperative adjuvant chemotherapy can be selected according to the physical performance status of the patient, and combined chemotherapy is preferred for patients with good physical performance. Presently, there is no high-quality evidence that molecular targeted therapy, immunotherapy, and cell therapy can be used in the postoperative adjuvant setting for pancreatic cancer or that they have any survival benefits. Further relevant clinical research is recommended.

Adjuvant chemotherapy should be started as soon as possible. For patients showing good recovery of physical performance postoperatively, the timing of initiating adjuvant chemotherapy should be controlled within 8 weeks after surgery as far as possible; for patients with poor physical performance, the time of initiation should not exceed 12 weeks after surgery. Generally, 6 to 8 cycles of chemotherapy over a total course of 24 weeks is recommended. Because some patients show early postoperative metastasis, a comprehensive baseline assessment that includes imaging studies should be performed before administering adjuvant chemotherapy.

Adjuvant chemotherapy should be continued for patients with pancreatic cancer who have previously undergone sequential radical surgery after neoadjuvant chemotherapy, after referring to the efficacy of neoadjuvant chemotherapy or after an MDT discussion and evaluation.

The role of postoperative adjuvant radiotherapy in delaying recurrence and improving prognosis is still controversial and lacks high-quality evidence. Postoperative adjuvant radiotherapy is recommended for patients with a residual tumor (R1 or R2 resection), regional lymph node metastasis, or vessel or nerve invasion. Further clinical studies are recommended.

Recommendation 32: Adjuvant chemotherapy should be started up to 8 weeks after surgery. Combination chemotherapy is the first-choice treatment, dependent on the physical performance status of the patient.

Quality of evidence: Moderate

Strength of recommendation: Strong

Standardized assessment of surgical pancreatic cancer specimens and the evaluation of surgical margin status

For ensuring specimen integrity, surgeons and pathologists should cooperate to complete the standardized assessment of specimens harvested during pancreaticoduodenectomy. The incisal margins of the specimens should be marked and described to objectively and accurately reflect the incisal margin status: marked areas include the anterior (ventral) side of the pancreas, posterior (dorsal) side of the pancreas, groove of the superior mesenteric vein, incisal margin of the superior mesenteric artery, broken end of the pancreas, incisal margin of the bile duct, stomach, and jejunum.

If pancreatic resection is combined with superior mesenteric vein or portal vein resection, vein involvement should be reported and classified according to the depth of infiltration as follows: involvement of the external membrane of the vein wall; involvement of all layers of the vein wall except the intima; and involvement of the whole vein wall.

In previous literature, R0 and R1 resections are defined by the presence of tumor cells on the margin surface. However, there is no significant difference in prognosis between R0 and R1 resections, and patients who under R0 resection still have a high local recurrence rate. It has been suggested that R0 or R1 resection should be defined based on the presence of tumor invasion within 1 mm from the resection margin. R1 resection is defined by the presence of tumor cell infiltration within 1 mm from the margin; R0 resection is defined by absence of tumor cell infiltration. Prognosis was significantly different between patients undergoing R0 and R1 resection when the presence of tumor invasion within 1 mm of the resection margin was used as the defined criterion.[61] Because of the anatomical location of pancreatic cancer and its relationship with surrounding blood vessels, R1 resection is performed in most patients. An R2 resection is considered when a positive incisal margin is detected by the naked eye.

The purpose of surgery is R0 resection, but because of the anatomic characteristics of the pancreas and the biological behavior of the tumor, it is difficult to avoid R1 resection. Nevertheless, R1 resection can improve the prognosis of patients. In contrast, the effect of palliative resection, especially R2 resection, on the improvement of prognosis remains debatable. Compared with palliative short circuit surgery, R2 resection fails to improve patients’ prognosis and quality of life and should therefore be avoided.

Recommendation 33: Standardized assessment of specimens harvested during pancreatoduodenectomy should involve a collaboration between surgeons and pathologists. The incisal margins of the specimens should be marked and described to objectively and accurately reflect the incisal margin status.

Quality of evidence: Moderate

Strength of recommendation: Strong

Recommendation 34: The “1 mm” principle should be used as the judgment standard for defining R0 or R1 incisal margins.

Quality of evidence: Moderate

Strength of recommendation: Weak

Chemotherapy, targeted therapy, and immunotherapy for unresectable pancreatic cancer

As the optimal regimen for comprehensive treatment of locally advanced or metastatic pancreatic cancer remains uncertain, relevant clinical studies should be performed. Active chemotherapy can alleviate symptoms, improve quality of life, and prolong survival. Based on physical performance status, the first choice is combined treatment, such as FOLFIRINOX, gemcitabine plus albumin-bound paclitaxel, or gemcitabine plus S1; for patients with poor physical performance, gemcitabine or S1 single-drug monotherapy can be selected. Gemcitabine combined with molecular targeted therapy is also a feasible option. If the tumor progresses after first-line chemotherapy, the second-line chemotherapy should be chosen under the consideration of patients’ physical performance, comorbidities, first-line drugs, and adverse reactions to chemotherapeutic drugs. Second-line chemotherapy is more effective than supportive care therapy. For patients with good physical status, Nanoliposomal irinotecan combined with fluorouracil and folinic acid,[62,63] or oxaliplatin with fluorouracil/folinic acid is recommended.[64] For patients with poor physical performance, gemcitabine or S1 monotherapy can also be selected.[65] All patients with locally advanced or metastatic pancreatic cancer should undergo genetic testing, including but not limited to testing for BRCA1/2, NTRK1/2/3, PALB2, ATM/ATR, and RAS mutations; this can help guide optimal drug selection and allow participation in clinical trials of new drugs. For patients with pancreatic cancer with NTRK gene fusion, larotrectinib or entrectinib is preferred for treatment.[66,67] For patients with BRCA1/2 mutations, a platinum-based chemotherapy regimen is preferred for first-line chemotherapy, such as FOLFIRINOX or gemcitabine plus cisplatin. If no progress is seen for ≥16 weeks after the administration of a platinum-based chemotherapy regimen, treatment with olaparib is recommended.[68] For patients with a germline BRCA1 mutation or homologous recombination repair pathway abnormalities, the same treatment can be applied. Nimotuzumab plus gemcitabine can prolong the overall survival of patients with locally advanced or metastatic pancreatic cancer with a wildtype KRAS gene or a wildtype KRAS gene combined with enhanced epidermal growth factor receptor (EGFR) expression.[69] Erlotinib combined with gemcitabine can be used in patients with an EGFR mutation. At present, evidence for the use of anti-angiogenesis drugs for advanced pancreatic cancer is still lacking.

Detection of microsatellite instability (MSI), mismatch repair (MMR), and tumor mutation burden should be performed in all patients with advanced pancreatic cancer. Immunosuppressors such as anti-PD-1 monoclonal antibodies are suggested for use in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic pancreatic cancer. There is no evidence that CTLA-4/PD-1/PD-L1 antibody, an immunosuppressant, can benefit patients with pancreatic cancer without the abovementioned molecular characteristics.

Other treatments include radiofrequency ablation, cryopreservation, high-intensity focused ultrasound, gamma knife radiation therapy, and the implantation of radioactive micron-sized particles. However, there is no clear evidence that these treatments can prolong the survival of patients with pancreatic cancer.

Recommendation 35: For patients with unresectable advanced pancreatic cancer, systemic treatment should be actively performed according to the patient's physical performance status. Combination treatment is preferred.

Quality of evidence: High

Strength of recommendation: Strong

Recommendation 36: All patients with unresectable advanced pancreatic cancer should participate in clinical trials; genetic testing should be performed to determine the optimal drug treatment.

Quality of evidence: Low

Strength of recommendation: Strong

Application and clinical significance of genetic testing in the diagnosis and treatment of pancreatic cancer

In recent years, high throughput second-generation sequencing plays an important role in the pathogenesis, molecular typing, and pharmacodynamics of pancreatic cancer. However, because of the complexity of molecular typing and the heterogeneity of tumors, the clinical significance of most detectable variations remains unclear. There are no effective drugs that target the common driver genes, such as KRAS, TP53, CDKN2A, and SMAD4, limiting the application of genomic detection in the clinical diagnosis and treatment of pancreatic cancer.

Biomarker-based targeting and immunotherapy have been increasingly used in the clinical treatment of pancreatic cancer. Nimotuzumab plus gemcitabine can prolong the overall survival of patients with locally advanced or distant metastatic pancreatic cancer with the wildtype KRAS gene and enhanced EGFR expression.[69] However, there are few such patients in clinical practice. The phase III POLO study confirmed that patients with advanced pancreatic cancer carrying a mutated BRCA1/2 gene can benefit from maintenance treatment with the poly (ADP-ribosyl) transferase inhibitor olaparib after platinum-based chemotherapy.[68] Drug treatment for cancers with mutated oncogenic drivers has confirmed that larotrectinib or entrectinib can be used to treat NTRK-mutated locally advanced or distant metastatic pancreatic cancer.[70] The monoclonal anti-PD-1 antibody is highly effective for MSI-H or dMMR metastatic pancreatic cancer.[71] In addition, some gene states can guide chemotherapy regimen selection; for example, patients with BRCA1/2- and PALB2-mutated pancreatic cancer are sensitive to platinum-based chemotherapy.

In addition to genetic testing, which is of clinical significance to guide pancreatic cancer treatment, treatable gene variations that have been confirmed in other types of tumors can be detected to identify additional treatment opportunities. These variations include but are not limited to those in homologous recombination repair pathway genes (except BRCA1/2 and PALB2), genes involved in homologous recombination repair deficiency (based on genomic scar scores), HER2 amplification, ALK fusion, and ROS1 fusion.

Recommendation 37: All patients with pancreatic cancer should be tested for susceptibility genes for pancreatic cancer; for people carrying a pathogenic or potentially pathogenic germline mutation, genetic counseling should be conducted in a professional institution or pancreatic cancer screening should be conducted in a high-volume pancreatic center.

Quality of evidence: Low

Strength of recommendation: Strong

Recommendation 38:BRCA1/2 mutations, PALB2 mutations, MSI-H/dMMR, and tumor mutation burden should be assessed in patients with pancreatic cancer.

Quality of evidence: High

Strength of recommendation: Strong

Recommendation 39: Tumor tissue is preferred for genetic testing. If testing using tumor tissue is not feasible, cell-free DNA testing can be considered.

Quality of evidence: Moderate

Strength of recommendation: Weak

Postoperative follow-up of patients with pancreatic cancer

Based on the highly malignant biological behavior of pancreatic cancer, patients subjected to radical resection have a high risk of tumor recurrence, and some patients develop local recurrence or distant metastasis early after surgery. Groot et al reviewed the clinical data of 957 pancreatic cancer patients who underwent surgery. The tumor recurrence rate during the follow-up period was 88.7%, and 51.5% of these patients showed local recurrence or distant metastasis within 1 year after surgery.[5] According to CPDC data of 3279 patients subjected to pancreatic cancer resection between 2016 and 2019, the tumor recurrence rate was 45.87% within 9 months after surgery. Therefore, regular, close, postoperative follow-up is extremely important. Within 2 years after surgery, it is recommended that blood tumor markers are evaluated every 3 months and that CT, MRI, and other imaging examinations are performed every 6 months. Thereafter, the evaluation of blood tumor markers every 6 months and CT, MRI, and other examinations every 12 months are recommended. If there are suspicious signs of recurrence, such as elevated blood tumor marker levels and enlarged lymph nodes, further investigation should be carried out in a timely manner. During the follow-up period, special attention should be paid to other surgical complications, such as pancreatic function and nutritional status, in addition to monitoring for tumor recurrence; cooperation with the MDT is essential for timely interventions for these compilations. From a psychosocial perspective, attention should be paid to psychological and spiritual counseling for end-stage pancreatic cancer patients, in addition to symptomatic treatment, to develop appropriate interventions that maximize patients’ quality of life.

Recommendation 40: There is a high risk of recurrence after pancreatic cancer surgery. Close follow-up and reexamination are required.

Quality of evidence: High

Strength of recommendation: Strong

Conclusion

These guidelines aim to provide guidance for standardized diagnosis and treatment of pancreatic cancer. The content of these guidelines cannot cover all clinical phenomena. In view of the complexity of the biological behavior of pancreatic cancer, heterogeneity between patients, limitations of existing clinical studies, and uncertainty of treatment effects, these guidelines should be implemented in clinical practice alongside the consideration of individual cases. Under the guidance of these recommendations, the selection of individualized treatment options can benefit patient prognosis.

Acknowledgments

We kindly thank Dr. Yuting Hou (Peking University First Hospital) for colored drawings within guidelines.

Author contributions

YZ led and directed the guidelines. YY, WW and XT prepared the manuscript. YY and WW equally participated into revising and logical consequence of the final manuscript. All the authors participated in the review and discussion of the contents of the guidelines and approved the final version of the manuscript.

Financial support

None.

Conflicts of interest

None.

Editor note: YY, WW, HC, TL, WL, YM, HW, XY, CY, TZ and YZ are Editorial Board members of Journal of Pancreatology. The article was subject to the journal's standard procedures, with peer review handled independently of these Editorial Board members and their research groups.

Ethics approval

Not applicable.

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Keywords:

Diagnosis; Guideline; Multidisciplinary team; Pancreatic cancer; Treatment

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