Surgical management of pancreatic cancer: an overview

Introduction

Pancreatic cancer remains one of the most lethal malignancies worldwide, with 30% 5-year overall survival rate after margin-negative pancreaticoduodenectomy for node-negative disease, whereas 10% for node-positive disease (1). Pancreatic ductal adenocarcinoma (PDAC) is the most common histological subtype. Despite advances in systemic therapies, surgical resection remains the central dogma of potential cure in PDAC. However, only about 15–20% of patients present with resectable disease, and even among these, survival outcomes remain suboptimal due to high recurrence rates. This review aims to provide a concise summary of current evidence on the surgical management of pancreatic cancer, focusing on patient selection, operative techniques, and perioperative care.

Epidemiology and clinical presentation

According to data from the World Health Organization Global Cancer Observatory in 2022, pancreatic cancer was ranked 12^th in terms of incidence, whereas ranked 6^th in terms of mortality among all types of cancers worldwide (2). In China, it was the 10^th most common cancer but ranked 6^th in terms of mortality in 2022. Locally, according to the latest Hong Kong Cancer Registry data in 2023 (3), pancreatic cancer was the 9^th most common malignancy in males (crude rate, 16.2), and ranked 4^th in the overall mortality rate of both sexes (crude rate, 12.2). In 2023, there were 1,049 new cases of pancreatic cancer, with an increasing trend observed in recent years.

The disease predominantly affects patient over 60 years of age, with a slight male predominance. Risk factors include smoking, chronic pancreatitis, diabetes mellitus, obesity, and genetic predispositions (e.g., BRCA mutations).

The clinical presentation of pancreatic cancer often relates to the location of the tumour. For tumour localised to the head of pancreas, which accounts for approximately 60–70%, patients usually presented with biliary obstruction, whereas the other 20–25% are body or tail tumours which tend to present at more advanced stages with more insidious, non-specific, complex symptomatology of pain, exocrine or endocrine pancreatic insufficiency, or even metastatic disease (4). Uncommonly, pancreatic masses are found incidentally on imaging performed for another reason, but the majority of them shall be cystic lesions, e.g., intraductal papillary mucinous neoplasm, which are known to be precursor lesions to exocrine pancreatic cancer.

The anatomical location of pancreatic tumours and their relationship to neighbouring vasculatures often determine the resectability, which would further discuss in the following section.

Clinical staging and resectability

The staging of pancreatic cancer is critical for prognosis and treatment planning. The most widely recognised system is the American Joint Committee on Cancer (AJCC) primary tumour, regional lymph nodal, and distant metastasis (TNM) staging system, 8^th edition (5). Below is a comprehensive overview and the corresponding stage groupings (see Table 1).

T (primary tumour):

• TX: primary tumour cannot be assessed;
• T0: no evidence of primary tumour;
• Tis: carcinoma in situ;
• T1: tumour ≤2 cm, limited to the pancreas;
  • T1a: tumour ≤0.5 cm;
  • T1b: tumour >0.5 and ≤1 cm;
  • T1c: tumour >1 and ≤2 cm;
• T2: tumour >2 and ≤4 cm, limited to the pancreas;
• T3: tumour >4 cm, limited to the pancreas;
• T4: tumour involves the celiac axis, superior mesenteric artery (SMA), and/or common hepatic artery (CHA) (unresectable primary tumour).

N (regional lymph nodes):

• NX: regional lymph nodes cannot be assessed;
• N0: no regional lymph node metastasis;
• N1: metastasis in 1–3 regional lymph nodes;
• N2: metastasis in ≥4 regional lymph nodes.

M (distant metastasis):

• M0: no distant metastasis;
• M1: distant metastasis present.

However, clinical staging alone does not dictate the treatment option, especially for localised pancreatic tumours without distant metastasis (6). It is of paramount importance to determine the resectability based on the imaging findings from high-quality, contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), sometimes supplementary endoscopic ultrasonography. The National Comprehensive Cancer Network (NCCN) guideline (6,7) categorizes pancreatic tumours into resectable, borderline resectable, and unresectable/locally advanced tumours based on arterial and venous involvement.

For a resectable tumour, it is defined to have no arterial tumour contact (celiac axis, SMA, or CHA) and no tumour contact with the superior mesenteric vein (SMV) or portal vein (PV) or ≤180° contact without vein contour irregularity.

Borderline resectable tumour is defined as a tumour with abutment (≤180°) of major arteries or limited venous involvement that is potentially reconstructible. For arterial criteria, these tumours must have contact ≤180° with SMA or celiac axis, or contact ≤180° with CHA without extension to the celiac axis or hepatic artery bifurcation, which renders reconstruction possible. For venous criteria, these tumours must have contact with SMV or PV >180°, or ≤180° with contour irregularity or narrowing, but the vein is still reconstructible, or short vein segment occlusion with suitable proximal/distal vessels for reconstruction. Although upfront resection might be possible, very often neoadjuvant therapy followed by re-evaluation imaging and surgical exploration has a role to increase the likelihood of an R0 resection.

Finally, unresectable/locally advanced tumours are defined to have tumour involvement of critical arteries or unreconstructible venous involvement. For arterial involvement, there shall be tumour contact >180° with SMA or celiac axis, or tumour contact >180° with CHA and/or extension to celiac axis or hepatic artery bifurcation. For venous Involvement, unreconstructible occlusion of SMV/PV (extensive thrombosis or lack of suitable vessel for anastomosis) should be present. Of note, classification and practice is variable across institutions based on local practice and surgeon expertise, and usually the consensus shall be drawn through a multidisciplinary meeting.

For initial staging of pancreatic cancer, a thin-cut, multiphase, contrast-enhanced “pancreatic protocol” type of CT of the abdomen is usually the choice of modality, as it was shown to have superior sensitivity approaching 100% for detecting suspicious pancreatic tumours, especially when tumours are large than 2 cm (8). Not surprisingly, the sensitivity might reduce if the tumours are small. Also, it is usually sufficient for surgeons to delineate the presence of vascular involvement and vascular anomaly to determine the surgical resectability (9), as well as the presence of distant metastasis (10). Positron emission tomography (PET) and endoscopic ultrasound (EUS) might be used as adjuncts in diagnosis and staging of pancreatic cancer, but they alone can not replace a well performed CT. PET shall be performed in circumstances where small volume occult distant metastases are suspected, or in borderline resectable cases. PET might also be advised for patients with high preoperative serum carbohydrate antigen 19.9 (CA19.9) level, which might correspond to chance of distant metastasis on presentation, but the cutoff has not yet been determined in international consensus. According to a prospective multicentre trial conducted in the United Kingdom, the routine supplementary use of PET scan could alter the staging in 10% of patients with suspected pancreatic cancer, whereas it also avoid unnecessary surgical resection in 20% of patients who was once determined to have resectable cancers solely based on CT (11).

Of note, the updated NCCN guideline and European Society of Medical Oncology (ESMO) guideline do not recommend the routine use of supplementary PET for the purpose of initial staging of pancreatic cancer. Furthermore, the additional cost of PET should be highlighted to patients and their families.

EUS is an emerging technique in managing many hepatopancreatobiliary diseases, for example, pancreatic cystic neoplasms, but yet its role in the context of pancreatic cancer is more related to its complementary ability of tissue acquisition. It might have an advantage in evaluating small and ambiguous tumours where the sensitivity of CT is lowered (12,13); however, the interpretation is highly operator dependent and very often requires expertise. Routine EUS-guided tissue acquisition, i.e., fine needle aspiration cytology or biopsy, is not recommended in the international consensus for patients who are surgical candidates and with clearly resectable disease. Upfront surgical resection shall be performed (14). EUS with fine needle tissue acquisition should be performed when there is a diagnostic dilemma where benign pathology has to be excluded, or in the context of borderline or locally advanced tumours where neoadjuvant chemotherapy shall be given, or in metastatic disease where histology is needed to confirm diagnosis and guide subsequent systemic treatment (15-17).

Preoperative biliary drainage (PBD)

For patients with resectable tumours presenting with obstructive jaundice, it may cause pruritus, malabsorption, coagulopathy due to vitamin K malabsorption, renal and hepatic dysfunction, and theoretically increased risk of postoperative complications. Therefore, it was believed that PBD would correct these detrimental defects and reduce perioperative morbidity. The drainage could be achieved in either an endoscopic or a percutaneous method. Yet, the results from previous clinical trials were inconsistent to show a definitive benefit (18-23). As one of the most cited landmark trial, the Dutch randomised controlled trial (RCT) (van der Gaag et al., N Engl J Med, 2010) (24) randomised 202 patients with pancreatic head tumours and obstructive jaundice with bilirubin level of 40 to 250 µmol/L to early surgery within 1 week after diagnosis vs. PBD with plastic stents followed by surgery after 4–6 weeks. It showed higher complication rate in PBD group (74%) compared to early surgery (39%) [relative risk in the early surgery group, 0.54; 95% confidence interval (CI): 0.41–0.71; P<0.001], whereas surgery-related complications occurred in 35 patients (37%) in the early-surgery group and in 48 patients (47%) in the biliary-drainage group (relative risk, 0.79; 95% CI: 0.57–1.11; P=0.14). Mortality rate was not significantly different between the two arms. Later, multiple meta-analyses (25-27) demonstrated higher complication rates (especially cholangitis, pancreatitis, and stent-related problems) with PBD vs. direct surgery, whereas there was no clear benefit in overall survival or reduction in serious postoperative complications.

According to current international guidelines [NCCN, ESMO, and American Society of Clinical Oncology (ASCO)] (7,28,29), routine PBD is not recommended. It is generally indicated in selected patients with acute cholangitis, debilitating symptoms (e.g., pruritus/malnutrition/renal dysfunction/coagulopathy), severe hyperbilirubinemia (i.e., >250 µmol/L), surgical delay due to logistical reasons, or anticipated neoadjuvant chemotherapy. The most preferred method of biliary drainage is internal stenting with endoscopic retrograde cholangiopancreatography (ERCP). Regarding the choice among plastic stents vs. self-expanding metallic stents (SEMS), a meta-analysis showed that SEMS in malignant distal biliary obstruction significantly longer stent patency with reduced stent occlusion [odds ratio (OR), 0.48; 95% CI: 0.34–0.67], and lower risk of post procedural cholangitis (OR, 0.46; 95% CI: 0.30–0.69) (30). The benefits were also consistently shown in other meta-analyses and other RCTs (31-34). The mean duration of patency of SEMS was shown to be >270 days, compared to 73 days of a plastic stent. Current international guidelines (NCCN, ESMO, and ASCO) recommend SEMS over plastic stents. Plastic stents may be considered if surgery is imminent (within 1–2 weeks) due to lower upfront cost and short-term need. Although many believe that metallic stents, especially bare stents, might incite an inflammatory reaction, causing stent incorporation into the bile duct wall, which makes it difficult to be removed and can therefore complicate the surgery, this could be of less concern with the newer fully covered metallic stents (35-37).

Surgical principles

Staging laparoscopy

Despite advances in imaging modalities, diagnostic laparoscopy remains a crucial role in detecting occult metastasis at the time of surgery. With reassuring preoperative studies, small liver or peritoneal metastases might be found at exploration in 8–15% of patients, which then conclude the operation (38). If the patient has concomitant unrelieved biliary obstruction or duodenal or gastric outlet obstruction, this patient might be benefited from palliative double bypass, i.e., gastrojejunostomy and hepatojejunostomy (39).

Margin negative resection

The resection of pancreatic tumours should comply strictly to the oncological surgical principles: en bloc resection, clear resection margin (R0 resection), and adequate lymphadenectomy. Surgeons should always make their best effort in achieving a clear surgical margin, as a positive margin has been shown by evidence to be associated with decreased survival (40,41). In a Whipple specimen, there are seven locations of resection margin status to be reported by pathologists, including anterior, posterior, medial or SMV groove, pancreatic parenchymal, bile duct, and bowel margin (42). There are different definitions of a negative margin, i.e., R0 resection, among international guidelines. For example, in the United States, where AJCC criteria (5) are used, a positive margin is defined when tumour cells are present at the edges of the specimen, whereas European guidelines define R0 as no tumour within 1mm of the margin. International Study Group on Pancreatic Surgery (ISGPS) recommended to report both margin “at the ink” and “within 1 mm” for clarity.

Lymphadenectomy

Standard lymphadenectomy as part of pancreatic cancer surgery is recommended in most of the established guidelines worldwide. For pancreatoduodenectomy, according to the consensus statement by the ISGPS, lymph node stations of 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b should be dissected and removed with the main specimen (43). They referred to lymph nodes in the suprapyloric, infrapyloric, anterior to CHA, hepatoduodenal ligament (bile duct/PV), anterior/posterior pancreaticoduodenal arteries, around SMA, anterior and posterior to the pancreatic head, respectively (see Table 2). Extended lymphadenectomy, which includes all 8 (CHA), 9 (celiac trunk), all 12, all 14, 16 (para-aortic), is not recommended as a Cochrane review in 2021 (44) demonstrated that extended lymphadenectomy increased operative time, also blood loss without survival benefit. A meta-analysis also concluded that the extended lymphadenectomy was associated with increased risk of surgical complications (lymphatic fistula: OR, 6.1, 95% CI: 1.0–35.3; delayed gastric emptying: OR, 2.0, 95% CI: 1.2–3.5; bile leak: OR, 2.6, 95% CI: 1.0–6.7; pancreatic leak: OR, 1.7, 95% CI: 1.0–2.9) (45). For distal pancreatectomy in treating pancreatic body and tail tumours, standard lymphadenectomy should include stations 10, 11, 18, 9, and 10, which consist of lymph nodes at the splenic hilum, proximal and distal splenic artery, inferior border of the pancreas body and tail, celiac trunk, and left gastric artery, respectively (see Table 3). AJCC recommended at least 12 lymph nodes to be resected for adequate staging (46).

Recognition of aberrant anatomy is pivotal in preoperative planning to avoid inadvertent injury to major vessels, oncologic compromise, or major complications (47). While many notable variants were described in the literature, two most valuable aberrant arterial variants that the surgeon must be particularly cautious are the replaced right and left hepatic arteries. Replaced right hepatic artery arises from the SMA instead of the proper hepatic artery, which is seen in ~10–15% of patients. It runs posterior to the PV and head of pancreas, which might have high risk of injury during uncinate dissection. The replaced left hepatic artery arises from the left gastric artery, which is seen in ~10% of patients (48).

Surgical technique

Pancreaticoduodenectomy (Whipple operation)

The conventional pancreaticoduodenectomy was first described in the 1930s and involves resection of the pancreatic head, duodenum, first 15 cm of jejunum, common bile duct, and gallbladder. It is the standard operation for cancer head of pancreas, and it’s usually performed in the following sequence:

• Staging laparoscopy for assessment of metastatic disease, if present, a formal laparotomy shall be avoided.
• Incision and exploration:
  • Upper midline or bilateral subcostal (Chevron) incision.
  • Assessment of metastatic disease: systematic inspection of the liver, peritoneum, and lymph nodes; frozen section if suspicious lesions are seen.
  • If distant metastasis or unresectable local disease is found, curative surgery shall be aborted. Palliative bypass surgery shall be performed depending on the patient’s clinical status.
• Mobilisation and exposure:
  • Division of the gastrocolic ligament to enter the lesser sac, expose anterior surface of the pancreas.
  • Kocher manoeuvre: duodenum is mobilised and the head of the pancreas from the retroperitoneum to expose the inferior vena cava (IVC). SMV is isolated.
• Assessment of resectability:
  • Palpation and visualisation of the PV, SMV, and SMA.
  • Check for vascular involvement—if present, assess technical feasibility of vascular resection and reconstruction.
• Cholecystectomy, hilar dissection, vascular control:
  • Cholecystectomy is performed to facilitate exposure and for biliary reconstruction.
  • Skeletonization of portal hepatis structures, standard lymphadenopathy.
  • Dissection and control of the CHA, gastroduodenal artery (GDA), and right gastric artery.
• En bloc resection:
  • Transection of the stomach or duodenum:
    • In classic Whipple, the distal stomach is divided (antrectomy).
    • In pylorus-preserving Whipple, the duodenum is divided just beyond the pylorus.
  • Division of the common hepatic duct above the cystic duct insertion.
  • Transection of the pancreatic neck anterior to the PV.
  • Transection of the proximal jejunum at around 10–15 cm distal to the ligament of Treitz and mobilise to the supracolic compartment.
  • Dissection of the uncinate process from the SMV and SMA, ligating small venous and arterial branches.
  • Intraoperative frozen sections of the bile duct margin and the pancreatic duct margin to confirm clearance from disease.
• Vascular reconstruction options include (49):
  • Primary end-to-end anastomosis if the resected segment is short (<2–3 cm).
  • Interposition grafts if the resected segment if long where direct anastomosis is not possible. Graft materials could be autologous or synthetic grafts or cryopreserved (cadaveric) vein grafts.
    • Autologous vein grafts include:
      • Internal jugular vein.
      • External iliac vein or femoral vein.
      • Left renal vein (if not needed for kidney drainage).
      • Great saphenous vein (rarely, due to small size).
      • Splenic vein or left gastric vein (for short segments, if available).
    • Synthetic (prosthetic) grafts:
      • Polytetrafluoroethylene (PTFE) or Dacron if autologous vein graft is not available but with higher risk of thrombosis and infection.
  • Patch venoplasty for partial (side-wall) resection of the vein. Patch can be fashioned from autologous vein (e.g., saphenous vein, peritoneal patch or pericardium (autologous or bovine).
• Reconstruction phase:
  • Pancreaticojejunostomy (PJ) [or pancreaticogastrostomy (PG)] to reconnect the pancreatic remnant to the jejunum (or stomach) for pancreatic drainage.
  • Techniques include duct-to-mucosa, invagination, with or without internal stenting or external stenting.
  • Hepaticojejunostomy to connect the common hepatic duct to the jejunum for billiard drainage.
  • Gastrojejunostomy or duodenojejunostomy to reconnect the stomach (or duodenum if pylorus-preserving) to the proximal jejunum to restore gastrointestinal continuity.
• Drain placement near the pancreatic and biliary anastomoses.

Conventional pancreaticoduodenectomy (Whipple operation) vs. pylorus-preserving pancreaticoduodenectomy (PPPD)

As compared with the classical Whipple operation, PPPD intentionally preserved the gastric antrum, pylorus, and short segment of proximal duodenum, as it theoretically reduces the occurrence of postoperative dumping and bile reflux gastritis (50). According to the Cochrane meta-analysis in 2016 (51), both are shown to have equivalent oncological outcomes in terms of long-term survival and surgical safety in terms of postoperative mortality and major morbidities (e.g., pancreatic fistula, biliary leakage, or postoperative bleeding). Delayed gastric emptying was shown to be significantly more common in PPPD (31% vs. 24%; OR, 3.03; 95% CI: 1.05–8.70). Meanwhile, PPPD was associated with shorter operative time, less intraoperative blood loss, and related blood transfusions.

Techniques used in pancreatic-enteric anastomosis

As postoperative pancreatic fistula (POPF) remains one of the most detrimental complications after pancreaticoduodenectomy, many variations in surgical techniques have been proposed aiming to reduce the occurrence of POPF.

PJ vs. pancreaticogastrostomy (PG)

Many randomised clinical trials were designed to compare PJ vs. PG as the optimal pancreatic enteric anastomosis; results were mostly inconsistent, some showed reduced incidence of POPF (52,53), whereas the others showed equivalent results (54-56). The RECOPANC trial in 2007 (57), as one of the largest multicentre RCTs, concluded that the rate of clinically significant POPF (grade B/C) was not statistically different, but PG was associated with more postoperative bleeding events. The similar equivalence in terms of clinically significant POPF/postoperative mortality between PG and PJ was also reported in a Cochrane review in 2017 (58). Therefore, it remains a surgeon’s preference based on expertise and experience in choosing between two techniques; the majority of surgeons might prefer PG over PJ in the context of soft and friable pancreas, which might make PJ technically more challenging to perform.

Duct-to-mucosa vs. invagination (dunking)

For PJ, historic literature has popularised two predominant techniques, i.e., end-to-side duct-to-mucosa anastomosis and invagination of the pancreatic remnant in either end-to-side or end-to-end manner (dunking) (59). Again, there is no concrete evidence favouring one over the other, and the choice remains a surgeon’s preference. A meta-analysis in 2018 (60) concluded no significant difference between the two techniques in terms of clinically significant POPF rates. A Cochrane review in 2022 also reported similar equivalence of both techniques (61).

Pancreatic stenting

The usage of a pancreatic stent directs the drainage of pancreatic secretion across the anastomosis; however, whether it prevents the occurrence of POPF remains uncertain. It could be performed in terms of internal stenting or external stenting, which requires removal weeks after the operation. Available evidence did not provide consistent and convincing results to indicate the superiority of stenting so far (62,63). A Cochrane review in 2016 (64) of four RCTs demonstrated overall reduction in incidence of POPF in stented patient but the difference was not statistically significant [risk ratio (RR), 0.67; 95% CI: 0.39–1.14], while another meta-analysis showed a significant reduction in rate of clinically relevant POPF with external stenting (OR, 0.50; 95% CI: 0.30–0.84; P=0.0009) (65).

Adjunctive tissue adhesives

There is no certain role of usage of tissue adhesives, e.g., fibrin glue, over the constructed pancreatic-enteric anastomosis in reducing the incidence of POPF (66,67).

Techniques used in gastrointestinal anastomosis

Apart from the aforementioned conventional and PPPD, there are variations utilised in achieving the gastrointestinal continuity, for example, with a single jejunal loop or with Roux-en-Y configuration or with Braun jejunojejunostomy (68). If a single jejunal loop is selected for reconstruction, PJ and HJ shall be constructed to the blind end of the jejunal loop, then the gastro/duodenojejunostomy shall be performed at around 45–60 cm distally. This form of reconstruction might theoretically reduce the occurrence of anastomotic ulcer but aggravate the bile reflux gastritis. Braun enteroenterostomy might provide an additional route of drainage of alkaline bile and pancreatic secretion to alleviate the bile reflux, but no convincing evidence is available to prove its effectiveness. Another common variation is the Roux-en-Y reconstruction using a separate Roux limb to perform the gastro/duodenojejunostomy and an additional jejunojejunostomy (69). Theoretically, it reduces bile reflux; however, based on limited available evidence, there appears no significant difference in terms of POPF or delayed gastric emptying compared with single jejunal loop reconstruction (70,71).

Routine vs. selective drain placement

Although the placement of surgical drains around the PJ theoretically converts a leakage into a controlled fistula and reduces the risk of intra-abdominal collection, routine placement of drains remains controversial, as evidence is conflicting (72,73). PANDRA trial in 2016 (74) as a two-centre randomized, controlled, noninferiority trial, concluded that omission of drains was not inferior in terms of postoperative re-intervention, postoperative mortality and morbidity, and it was superior in terms of clinically relevant pancreatic fistula rate (grade B/C: drain 11.9% vs. no-drain 5.7%, P=0.030) and fistula-associated complications (drain 26.4% vs. no drain 13.0%, P=0.0008). Cochrane meta-analysis in 2025 (75) of 12 randomised clinical trials did not demonstrate a concrete benefit in reducing surgical morbidity and mortality, but it showed that early drain removal in patient with a low risk of POPF was probably associated with less intra-abdominal infection rate.

Open vs. minimally invasive (MIS) pancreaticoduodenectomy

Open pancreaticoduodenectomy has remained the gold standard for resection of pancreatic head tumours for decades, with recent advances in surgical technology, especially the revolutionary robotic surgery, the role and benefit of MIS surgery in such complex surgery have been a hot topic in research. Earlier evidence from retrospective studies showed MIS pancreaticoduodenectomy had the advantage of lower intraoperative blood loss, shorter hospital stay, fewer wound infections, while had comparable results over the rate of overall mortality, reoperations, vascular resection, clinically relevant pancreatic fistula, delayed gastric emptying, and bile leakage (76). The results from two RCTs, one from India in 2017 (77) and the PADULAP RCT from Spain in 2018 (78), also echoed with the former evidence. However, surprisingly the more recent LEOPARD-2 trial in Netherlands (79) published contrary results, as it showed MIS pancreaticoduodenectomy was associated with higher 90-day complication-related mortality (10% in the laparoscopic pancreatoduodenectomy group vs. 2% in the open pancreatoduodenectomy group; RR, 4.90; 95% CI: 0.59–40.44; P=0.20), higher rate of severe postoperative complications (50% vs. 3%) but no improvement in the rapidity of functional recovery (10 vs. 8 days) (log-rank P=0.80). Of note, the trial was conducted in a high-volume centre with experienced surgeons performing the surgeries, and the trial was therefore prematurely terminated. Robotic-assisted pancreaticoduodenectomy has adopted the advantages of robotic operation to aid in the complex surgery, including the 540-degree wrist articulation, tremor stabilization, etc. Similar to laparoscopic surgery, it could be associated with less intraoperative blood loss, shorter hospital stay, fewer wound infections than open surgery, but with longer operative time. However, the overall oncology outcomes or major surgical mortality and morbidities were shown all comparable to conventional open surgery so far (80,81).

Distal pancreatectomy

For cancer in the pancreas located to the left of the SMA and SMV, distal pancreatectomy should be performed. It involves resection of the body and tail of the pancreas, with or without preserving the spleen. Preoperative vaccination against encapsulated organisms (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae) shall be mandatory for all patients. If not possible, after distal pancreatectomy with concomitant splenectomy, all patients should receive immunisation 2 weeks after surgery.

The operation is usually performed in an orderly sequence as follows:

• Staging laparoscopy for assessment of metastatic disease, if present, a formal laparotomy shall be avoided.
• Incision and exploration:
  • Upper midline or left subcostal incision in open approach, port placement if laparoscopic or robotic approach in selected patients.
  • Assessment of metastatic disease: systematic inspection of the liver, peritoneum, and lymph nodes; frozen section if suspicious lesions are seen.
  • If distant metastasis or unresectable local disease is found, curative surgery shall be aborted.
• Exposure and mobilization:
  • Division of the gastrocolic ligament to enter the lesser sac and expose the anterior surface of the pancreas.
  • Division of the gastrosplenic ligament and short gastric vessels to separate the greater curvature of the stomach and the spleen. Retraction of the stomach superiorly.
  • Mobilisation of the splenic flexure of the colon downward to expose the lower border of the pancreas. Division of the splenocolic ligament and lateral peritoneal attachment of the spleen.
  • Mobilisation of the pancreas from the retroperitoneum by developing the plane posterior to the pancreas.
  • Incision of the peritoneum along the superior border of the pancreas to identify the splenic artery.
• En bloc resection:
  • Localisation of the pancreatic tumour decides the transection plane of the pancreas to ensure R0 resection. It can be performed by palpation or with the usage of intraoperative ultrasound.
  • Transection of the pancreas with scalpel, electrocautery, or vascular stapler. Staple line might be reinforced with suture.
  • Frozen section of the pancreatic duct margin should be sent to confirm clearance from disease.
  • Standard lymphadenectomy should be performed.
  • If splenectomy is planned, the splenic artery should be divided by suture ligation or vascular stapler. Splenic vein could be divided separately or along with the pancreas with the use of stapler.
• Drain placement at the pancreatic bed.

Concomitant splenectomy vs. spleen-preserving distal pancreatectomy

For malignant pancreatic tumours located in the distal pancreas, usually distal pancreatectomy is performed with concomitant splenectomy in order to assure an R0 resection as well as adequate lymphadenectomy around the splenic vessels for proper staging and clearance of disease. Sampling of at least 15 lymph nodes is advocated (46). For small neuroendocrine tumours or premalignant pancreatic cystic lesions with no obvious suspicious of lymph node metastasis or high-grade pathology, spleen-preserving distal pancreatectomy could be attempted. There are two main techniques used in spleen preservation, namely the Warshaw (82) and the Kimura (83) technique. The former involves division of the main splenic artery and vein, but preserves short gastric vessels for perfusion to the spleen, whereas the latter preserves both the splenic artery and vein but meticulously ligates the small branches supplying or draining the pancreatic body and tail. Although the Warshaw technique could be less technically demanding to perform, it was shown to be associated with more postoperative hypersplenism, splenic infarct, and left side portal hypertension resulting in gastric varices. Meanwhile, the Kimura technique might not be feasible if the tumours are close or adherent to the main splenic vessels (84,85).

Techniques of pancreatic stump closure

Pancreatic neck could be transected either by staplers with or without reinforcement or by electrocautery, followed by hand-sewn closure of the pancreatic remnant (86). According to a Cochrane review in 2025 (87) based on 3 multicentre RCTs, both techniques were comparable in terms of POPF, overall postoperative mortality, or operative time. Therefore, it remains the preference of the surgeon to choose, for example, some surgeons might prefer sharp transection of the pancreas followed by hand-sewn suture ligation of the pancreatic duct if the pancreas is deemed thick for stapler to seal. With the aim to further reduce the POPF, there are adjuncts designed to reinforce the transection line. Some surgeons might prefer to use staples line reinforcement materials while using staplers, examples include bioabsorbable staple line mesh product (Seamguard) (88) or bioabsorbable polyglycolic acid polymer (Neoveil) (89,90). Some might reinforce the staple or non-staple line of transection with a vascularised flap for buttressing, and options include omental patch, falciform ligament, round ligament, or seromuscular jejunal patch (91,92). Some surgeons might use fibrin glue or perform a pancreaticoenteric anastomosis, i.e., PJ or PG (93). In a network meta-analysis in 2019 (94) involving 16 RCTs and comparing eight techniques, i.e., stapler, suture, ablation, anastomosis, glue, patch, mesh, and patch with glue, it concluded that patch reinforcement after stapled or sutured closure of pancreatic stump was associated with least occurrence of clinically relevant POPF, lower rates of overall complications and 30-day mortality. Among the choices of vascularised patch, round ligament was shown to be superior than seromuscular jejunal patch in terms of clinically relevant POPF rate.

Open vs. MIS distal pancreatectomy

Compared to pancreaticoduodenectomy, MIS distal pancreatectomy is more commonly performed in high-volume centres by experienced laparoscopic surgeons nowadays. The multicentre, patient-blinded LEOPARD trial in 2019 (95) involving patient with benign, premalignant, and malignant conditions, demonstrated that MIS distal pancreatectomy had less intraoperative blood loss but a longer operative time. Among those cancer patients, the oncological outcome, including the margin-positive rates and lymph nodes harvested, were all comparable, even the MIS group had a faster time to functional recovery and shorter hospital stay. Robotic distal pancreatectomy was shown to have similar results compared to open surgery (96,97).

Extended resection

Radical antegrade modular pancreatosplenectomy (RAMPS)

While distal pancreatectomy has been the established gold standard of treatment for distal pancreatic tumour, it is sometimes bounded with limitations of inadequate posterior resection margin and inadequate lymph node harvest, especially when dealing with bulky tumours with peripancreatic invasion, for example, the left adrenal gland. RAMPS is a novel surgical approach introduced with Dr. Strasberg in 2003 (98), and it has quickly been gaining popularity worldwide. “Radical” emphasises complete, R0 resection with wide posterior clearance, “antegrade” refers to dissection from medial to lateral as opposed to the conventional lateral to medial approach. “Modular” means that the posterior dissection plane is tailored according to the tumour location and degree of invasion, either anterior or posterior.

The procedure starts at the pancreatic neck with a medial-to-lateral approach. Pancreas is transected anterior to SMV, with the splenic artery and vein controlled at their origins. Anterior RAMPS is performed for tumours limited to the pancreas and anterior to the left adrenal gland and kidney, in which the posterior dissection plane is anterior to the left adrenal gland and Gerota’s fascia. Posterior RAMPS is performed for tumours near or invading the left adrenal gland or Gerota’s fascia, in which the posterior dissection plane is behind the left adrenal gland and Gerota’s fascia. Systematic dissection of lymph nodes is performed, including splenic artery and vein (station 11), celiac axis (station 9), CHA (station 8), SMA (station 14), splenic hilum (station 10), and posterior pancreatic nodes (station 13). Otherwise, the lateral mobilisation and splenectomy are performed as in conventional distal pancreatectomy.

As evidence is still emerging, RAMPS, compared to conventional distal pancreatectomy, was shown to have advantages in posterior margin clearance and lymph node harvest (99). A meta-analysis of six retrospective studies published in 2017 (100) showed that RAMPS was associated with a high R0 resection rate (OR, 2.19; 95% CI: 1.16–4.13; P=0.02) and a higher mean lymph node harvest rate [weighted mean difference (WMD), 7.06; 95% CI: 4.52–9.60; P<0.01]. However, recurrence rate, overall survival, and disease-free survival were not shown to have statistically superior in this meta-analysis. High-level RCTs are yet to be published.

Distal pancreatectomy with celiac axis resection (DP-CAR)

In selected patients with locally advanced pancreatic neck/body tumours with involvement of the celiac axis, an aggressive approach of DP-CAR (known as the modified Appleby procedure) could be adopted (101). As usually involvement of celiac axis is classified as at least borderline resectable, if not locally advanced disease by NCCN guideline, patients should be managed with neoadjuvant therapy instead of upfront resection, and re-evaluated with a post treatment re-staging scan and discussed in a multidisciplinary meeting involving oncologist, surgeon and radiologist to carefully select those patients who could potentially benefit from such aggressive form of resection (102). The key anatomical principle of celiac axis resection is to maintain blood flow to the stomach and liver by means of retrograde flow from the SMA through the patent pancreaticoduodenal arcades to the GDA, then to the right gastric and gastroepiploic arteries and hepatic proper artery.

Preoperatively, the selected patients should undergo high-resolution cross-sectional imaging (i.e., CT or MRI) with angiography to properly evaluate the latency of the aforementioned collateral circulation. Sometimes, digital subtraction angiography is also required. Intraoperatively, the exploration, mobilisation, and pancreatic transection are performed similarly as the standard distal pancreatectomy. The celiac axis is dissected, and test clamping of the CHA or intraoperative Doppler ultrasound is performed to confirm hepatic perfusion. Then the celiac axis is resected en bloc with the tumour. If there is evidence of arterial insufficiency from the SMA collaterals, the options remain to be primary anastomosis between the celiac artery stump and the CHA or arterial reconstruction with interposition grafts.

For such a complex operation, the main surgical complication of concern shall be the risk of hepatic and gastric ischemia. Early studies reported high perioperative morbidity and mortality, but more recent series with careful patient selection and preoperative planning showed improved rate of morbidity and higher R0 resection rate (90%) in high-volume expert centre (103,104). An Asian meta-analysis published in 2022 concluded that DP-CAR, compared to standard distal pancreatectomy was associated lower R0 resection (RR, 0.76; 95% CI: 0.66–0.88; P=0.0002) and 3-year survival rates (RR, 0.65; 95% CI: 0.43–0.98; P=0.04), higher postoperative mortality rates (RR, 2.48; 95% CI: 1.02–6.03; P=0.04), and longer operation time and hospital stay. However, there was no statistically significant difference in terms of 1-year (RR, 0.84; 95% CI: 0.57–1.23; P=0.37), 2-year survival rate (RR, 0.70; 95% CI: 0.45–1.10; P=0.12), and it apparently provided better survival compared to non-surgical palliative treatment (105). Therefore, careful patient selection and preoperative planning are of paramount importance for DP-CAR, and it should be performed in a high-volume centre with expertise and with a multidisciplinary approach.

Total pancreatectomy

For completeness of discussion, it is crucial to describe the option of total pancreatectomy for the treatment of extensive pancreatic cancer. It is never the favourite option for surgeons, and it is usually performed when the tumours cannot be resected with a less extensive approach. For example, it is indicated in the circumstances where the pancreatic tumour is infiltrative and has a tremendous disease burden, rendering the pancreatic remnant functionally insufficient or with concomitant premalignant lesions (e.g., intraductal papillary mucinous neoplasm with high-risk stigmata or worrisome features) or repeated positive intraoperative frozen section on pancreatic ductal margin (106,107).

Technically, it is the combination of pancreaticoduodenectomy and distal pancreatectomy. From the previous retrospective studies, it was shown that total pancreatectomy did not offer a statistically significant survival benefit than less extensive resection (108,109), meanwhile it inherently sacrifices the endocrine and exocrine functions of the pancreas, leading to significant postoperative surgical morbidities, i.e., brittle diabetes and malnutrition (110). Nearly all pancreatic patients would develop diabetes with similar clinical course as type 1 diabetes mellitus (111,112). Often their blood glucose level could be challenging to control without an endocrinologist’s input, and as a result these patients could suffer from complications from the poorly controlled diabetes, in both acute and chronic sequelae, for example diabetic ketoacidosis, symptomatic hypoglycemic episodes, and long-term microvascular/macrovascular complications. With loss of pancreatic ability of secreting lipase for the digestion of fat as well as fat-soluble nutrients, these patients postoperatively must be provided lifelong pancreatic enzyme supplements to improve the digestion, steatorrhea, and gastrointestinal symptoms (113).

Irreversible electroporation (IRE) and other ablative therapies

For locally advanced pancreatic cancer, for example, unresectable tumours with major vascular involvement or in adjuncts to resection for better margin clearance, an emerging non-thermal ablative technique, known as IRE, was a potential option of treatment (114). IRE uses short, high-voltage electrical pulses to create permanent nanopores in cell membranes, leading to apoptosis of the cells. As it does not generate thermal energy, unlike radiofrequency or microwave ablation, it preserves extracellular matrix, blood vessels, and bile ducts.

It can be performed under general anaesthesia with deep neuromuscular blockade, either laparoscopically or in an open approach for pancreatic cancer, or less commonly percutaneously. After exploration and adequate mobilisation, the tumour is localised, and multiple needle electrodes are placed around or through the tumour under image guidance.

As it is an emerging technique in treating locally advanced pancreatic cancer, high-level evidence is scarce. The major procedure-related complications reported were pancreatitis, bleeding, duodenal injury, and PV thrombosis, whereas the procedure-related mortality was <5%. The key series evaluating the efficacy of this novel treatment was published in 2015 (115), involving 200 patients with locally advanced pancreatic cancer treated with IRE alone or with resection plus IRE. It showed that the IRE, comparing with historical cohorts receiving conventional chemoradiation, improved the median overall survival rate to 18–23 months (vs. 11–16 months for chemotherapy alone). Some studies also reported improved pain control and quality of life (116,117). However, due to a lack of high-level evidence, IRE remains experimental and is currently not recommended as standard treatment according to the latest NCCN and ESMO guidelines, and should be performed within clinical trials.

Apart from IRE, alternative options include radiofrequency ablation and microwave ablation, which utilise thermal energy to destroy tumour cells, and are currently under clinical research. Similar to IRE, the indication of thermal ablative therapies remains for palliation for locally advanced, unresectable pancreatic cancer. Available data from multiple case series and retrospective studies (118-121) involving a small number of patients might demonstrate an acceptable clinical and technical success rate, especially by endoscopic means; however, the overall safety profile remained a serious concern, and the effect on overall survival was uncertain.

Conclusions

Despite advances in surgical techniques and technology, pancreatic cancer remains one of the most lethal malignancies worldwide. It is an increasingly prevalent disease entity which is particularly challenging to manage, and very often requires multidisciplinary input and tailored treatment for the individual patient.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Eric C. H. Lai) for the series “Carcinoma of Pancreas” published in Chinese Clinical Oncology. The article has undergone external peer review.

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-25-86/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-25-86/coif). The series “Carcinoma of Pancreas” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Allen PJ, Kuk D, Castillo CF, et al. Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma. Ann Surg 2017;265:185-91.
2. Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer. 2024. Available online: https://gco.iarc.who.int/today
3. Hong Kong Cancer Registry. Overview of Hong Kong Cancer Statistics of 2023. 2025. Available online: https://www3.ha.org.hk/cancereg
4. Porta M, Fabregat X, Malats N, et al. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clin Transl Oncol 2005;7:189-97. [Crossref] [PubMed]
5. Kakar S, Pawlik TM, Allen PJ, et al. Exocrine pancreas. In: Amin M, Edge SB, Greene FL, et al., editor. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2016:337-47.
6. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med 2014;371:2140-1. [Crossref] [PubMed]
7. National Comprehensive Cancer Network. NCCN Guidelines: Pancreatic Adenocarcinoma. 2025. Available online: https://www.nccn.org/guidelines/guidelines-detail?id=1455
8. Valls C, Andía E, Sanchez A, et al. Dual-phase helical CT of pancreatic adenocarcinoma: assessment of resectability before surgery. AJR Am J Roentgenol 2002;178:821-6. [Crossref] [PubMed]
9. Kaneko OF, Lee DM, Wong J, et al. Performance of multidetector computed tomographic angiography in determining surgical resectability of pancreatic head adenocarcinoma. J Comput Assist Tomogr 2010;34:732-8. [Crossref] [PubMed]
10. Satoi S, Yamamoto H, Takai S, et al. Clinical impact of multidetector row computed tomography on patients with pancreatic cancer. Pancreas 2007;34:175-9. [Crossref] [PubMed]
11. Ghaneh P, Hanson R, Titman A, et al. PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer. Health Technol Assess 2018;22:1-114. [Crossref] [PubMed]
12. Dewitt J, Devereaux BM, Lehman GA, et al. Comparison of endoscopic ultrasound and computed tomography for the preoperative evaluation of pancreatic cancer: a systematic review. Clin Gastroenterol Hepatol 2006;4:717-25; quiz 664. [Crossref] [PubMed]
13. Toft J, Hadden WJ, Laurence JM, et al. Imaging modalities in the diagnosis of pancreatic adenocarcinoma: A systematic review and meta-analysis of sensitivity, specificity and diagnostic accuracy. Eur J Radiol 2017;92:17-23. [Crossref] [PubMed]
14. Függer R, Gangl O, Fröschl U. Clinical approach to the patient with a solid pancreatic mass. Wien Med Wochenschr 2014;164:73-9. [Crossref] [PubMed]
15. ASGE Standards of Practice Committee. The role of endoscopy in the evaluation and management of patients with solid pancreatic neoplasia. Gastrointest Endosc 2016;83:17-28. [Crossref] [PubMed]
16. Kitano M, Yoshida T, Itonaga M, et al. Impact of endoscopic ultrasonography on diagnosis of pancreatic cancer. J Gastroenterol 2019;54:19-32. [Crossref] [PubMed]
17. Chan SL, Chiang CL, Chok KSH, et al. Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma. Hong Kong Med J 2024;30:147-62. [PubMed]
18. Hatfield AR, Murray RS. Pre-operative biliary drainage in patients with obstructive jaundice. A comparison of the percutaneous transhepatic and endoscopic transpapillary routes. S Afr Med J 1981;60:737-42. [PubMed]
19. McPherson GA, Benjamin IS, Hodgson HJ, et al. Pre-operative percutaneous transhepatic biliary drainage: the results of a controlled trial. Br J Surg 1984;71:371-5. [Crossref] [PubMed]
20. Pitt HA, Gomes AS, Lois JF, et al. Does preoperative percutaneous biliary drainage reduce operative risk or increase hospital cost? Ann Surg 1985;201:545-53. [Crossref] [PubMed]
21. Smith RC, Pooley M, George CR, et al. Preoperative percutaneous transhepatic internal drainage in obstructive jaundice: a randomized, controlled trial examining renal function. Surgery 1985;97:641-8. [PubMed]
22. Lai EC, Mok FP, Fan ST, et al. Preoperative endoscopic drainage for malignant obstructive jaundice. Br J Surg 1994;81:1195-8. [Crossref] [PubMed]
23. Eshuis WJ, van der Gaag NA, Rauws EA, et al. Therapeutic delay and survival after surgery for cancer of the pancreatic head with or without preoperative biliary drainage. Ann Surg 2010;252:840-9. [Crossref] [PubMed]
24. van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med 2010;362:129-37. [Crossref] [PubMed]
25. Fang Y, Gurusamy KS, Wang Q, et al. Pre-operative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev 2012;2012:CD005444. [Crossref] [PubMed]
26. Fang Y, Gurusamy KS, Wang Q, et al. Meta-analysis of randomized clinical trials on safety and efficacy of biliary drainage before surgery for obstructive jaundice. Br J Surg 2013;100:1589-96. [Crossref] [PubMed]
27. Scheufele F, Schorn S, Demir IE, et al. Preoperative biliary stenting versus operation first in jaundiced patients due to malignant lesions in the pancreatic head: A meta-analysis of current literature. Surgery 2017;161:939-50. [Crossref] [PubMed]
28. Khorana AA, McKernin SE, Berlin J, et al. Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. J Clin Oncol 2019;37:2082-8. [Crossref] [PubMed]
29. Conroy T, Pfeiffer P, Vilgrain V, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023;34:987-1002. [Crossref] [PubMed]
30. Moole H, Jaeger A, Cashman M, et al. Are self-expandable metal stents superior to plastic stents in palliating malignant distal biliary strictures? A meta-analysis and systematic review. Med J Armed Forces India 2017;73:42-8. [Crossref] [PubMed]
31. Davids PH, Groen AK, Rauws EA, et al. Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet 1992;340:1488-92. [Crossref] [PubMed]
32. Moss AC, Morris E, Leyden J, et al. Malignant distal biliary obstruction: a systematic review and meta-analysis of endoscopic and surgical bypass results. Cancer Treat Rev 2007;33:213-21. [Crossref] [PubMed]
33. Yoon WJ, Ryu JK, Yang KY, et al. A comparison of metal and plastic stents for the relief of jaundice in unresectable malignant biliary obstruction in Korea: an emphasis on cost-effectiveness in a country with a low ERCP cost. Gastrointest Endosc 2009;70:284-9. [Crossref] [PubMed]
34. Sawas T, Al Halabi S, Parsi MA, et al. Self-expandable metal stents versus plastic stents for malignant biliary obstruction: a meta-analysis. Gastrointest Endosc 2015;82:256-267.e7. [Crossref] [PubMed]
35. Park DH, Kim MH, Choi JS, et al. Covered versus uncovered wallstent for malignant extrahepatic biliary obstruction: a cohort comparative analysis. Clin Gastroenterol Hepatol 2006;4:790-6. [Crossref] [PubMed]
36. Yoon WJ, Lee JK, Lee KH, et al. A comparison of covered and uncovered Wallstents for the management of distal malignant biliary obstruction. Gastrointest Endosc 2006;63:996-1000. [Crossref] [PubMed]
37. Loew BJ, Howell DA, Sanders MK, et al. Comparative performance of uncoated, self-expanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial. Gastrointest Endosc 2009;70:445-53. [Crossref] [PubMed]
38. Gemenetzis G, Groot VP, Blair AB, et al. Incidence and risk factors for abdominal occult metastatic disease in patients with pancreatic adenocarcinoma. J Surg Oncol 2018;118:1277-84. [Crossref] [PubMed]
39. Kazanjian KK, Reber HA, Hines OJ. Laparoscopic gastrojejunostomy for gastric outlet obstruction in pancreatic cancer. Am Surg 2004;70:910-3. [Crossref] [PubMed]
40. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000;4:567-79. [Crossref] [PubMed]
41. Raut CP, Tseng JF, Sun CC, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg 2007;246:52-60. [Crossref] [PubMed]
42. Bockhorn M, Uzunoglu FG, Adham M, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2014;155:977-88. [Crossref] [PubMed]
43. Tol JA, Gouma DJ, Bassi C, et al. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 2014;156:591-600. [Crossref] [PubMed]
44. Staerkle RF, Vuille-Dit-Bille RN, Soll C, et al. Extended lymph node resection versus standard resection for pancreatic and periampullary adenocarcinoma. Cochrane Database Syst Rev 2021;1:CD011490. [PubMed]
45. Sun J, Yang Y, Wang X, et al. Meta-analysis of the efficacies of extended and standard pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas. World J Surg 2014;38:2708-15. [Crossref] [PubMed]
46. Tomlinson JS, Jain S, Bentrem DJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg 2007;142:767-723; discussion 773-4. [Crossref] [PubMed]
47. Shukla PJ, Barreto SG, Kulkarni A, et al. Vascular anomalies encountered during pancreatoduodenectomy: do they influence outcomes? Ann Surg Oncol 2010;17:186-93. [Crossref] [PubMed]
48. Chamberlain RS, El-Sedfy A, Rajkumar D. Aberrant hepatic arterial anatomy and the whipple procedure: lessons learned. Am Surg 2011;77:517-26. [Crossref] [PubMed]
49. Younan G, Tsai S, Evans DB, et al. Techniques of Vascular Resection and Reconstruction in Pancreatic Cancer. Surg Clin North Am 2016;96:1351-70. [Crossref] [PubMed]
50. Hackert T, Probst P, Knebel P, et al. Pylorus Resection Does Not Reduce Delayed Gastric Emptying After Partial Pancreatoduodenectomy: A Blinded Randomized Controlled Trial (PROPP Study, DRKS00004191). Ann Surg 2018;267:1021-7. [Crossref] [PubMed]
51. Hüttner FJ, Fitzmaurice C, Schwarzer G, et al. Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma. Cochrane Database Syst Rev 2016;2:CD006053. [Crossref] [PubMed]
52. Takano S, Ito Y, Watanabe Y, et al. Pancreaticojejunostomy versus pancreaticogastrostomy in reconstruction following pancreaticoduodenectomy. Br J Surg 2000;87:423-7. [Crossref] [PubMed]
53. Topal B, Fieuws S, Aerts R, et al. Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy for pancreatic or periampullary tumours: a multicentre randomised trial. Lancet Oncol 2013;14:655-62. [Crossref] [PubMed]
54. Bassi C, Falconi M, Molinari E, et al. Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy: results of a comparative study. Ann Surg 2005;242:767-71, discussion 771-3. [Crossref] [PubMed]
55. Duffas JP, Suc B, Msika S, et al. A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy. Am J Surg 2005;189:720-9. [Crossref] [PubMed]
56. Wellner UF, Sick O, Olschewski M, et al. Randomized controlled single-center trial comparing pancreatogastrostomy versus pancreaticojejunostomy after partial pancreatoduodenectomy. J Gastrointest Surg 2012;16:1686-95. [Crossref] [PubMed]
57. Keck T, Wellner UF, Bahra M, et al. Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial. Ann Surg 2016;263:440-9. [Crossref] [PubMed]
58. Cheng Y, Briarava M, Lai M, et al. Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction for the prevention of postoperative pancreatic fistula following pancreaticoduodenectomy. Cochrane Database Syst Rev 2017;9:CD012257. [Crossref] [PubMed]
59. Kennedy EP, Yeo CJ. Dunking pancreaticojejunostomy versus duct-to-mucosa anastomosis. J Hepatobiliary Pancreat Sci 2011;18:769-74. [Crossref] [PubMed]
60. Kilambi R, Singh AN. Duct-to-mucosa versus dunking techniques of pancreaticojejunostomy after pancreaticoduodenectomy: Do we need more trials? A systematic review and meta-analysis with trial sequential analysis. J Surg Oncol 2018;117:928-39. [Crossref] [PubMed]
61. Hai H, Li Z, Zhang Z, et al. Duct-to-mucosa versus other types of pancreaticojejunostomy for the prevention of postoperative pancreatic fistula following pancreaticoduodenectomy. Cochrane Database Syst Rev 2022;3:CD013462. [PubMed]
62. Winter JM, Cameron JL, Campbell KA, et al. Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial. J Gastrointest Surg 2006;10:1280-90; discussion 1290. [Crossref] [PubMed]
63. Poon RT, Fan ST, Lo CM, et al. External drainage of pancreatic duct with a stent to reduce leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy: a prospective randomized trial. Ann Surg 2007;246:425-33; discussion 433-5. [Crossref] [PubMed]
64. Dong Z, Xu J, Wang Z, et al. Stents for the prevention of pancreatic fistula following pancreaticoduodenectomy. Cochrane Database Syst Rev 2013;CD008914. [PubMed]
65. Patel K, Teta A, Sukharamwala P, et al. External pancreatic duct stent reduces pancreatic fistula: a meta-analysis and systematic review. Int J Surg 2014;12:827-32. [Crossref] [PubMed]
66. Lillemoe KD, Cameron JL, Kim MP, et al. Does fibrin glue sealant decrease the rate of pancreatic fistula after pancreaticoduodenectomy? Results of a prospective randomized trial. J Gastrointest Surg 2004;8:766-72; discussion 772-4. [Crossref] [PubMed]
67. Lai M, Zhou S, He S, et al. Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. Cochrane Database Syst Rev 2023;6:CD009621. [PubMed]
68. Strasberg SM, Drebin JA, Soper NJ. Evolution and current status of the Whipple procedure: an update for gastroenterologists. Gastroenterology 1997;113:983-94. [Crossref] [PubMed]
69. Tsalis K, Antoniou N, Koukouritaki Z, et al. Successful treatment of recurrent cholangitis by constructing a hepaticojejunostomy with long Roux-en-Y limb in a long-term surviving patient after a Whipple procedure for pancreatic adenocarcinoma. Am J Case Rep 2014;15:348-51. [Crossref] [PubMed]
70. Ke S, Ding XM, Gao J, et al. A prospective, randomized trial of Roux-en-Y reconstruction with isolated pancreatic drainage versus conventional loop reconstruction after pancreaticoduodenectomy. Surgery 2013;153:743-52. [Crossref] [PubMed]
71. Busquets J, Martín S, Fabregat J, et al. Randomized trial of two types of gastrojejunostomy after pancreatoduodenectomy and risk of delayed gastric emptying (PAUDA trial). Br J Surg 2019;106:46-54. [Crossref] [PubMed]
72. Petrowsky H, Demartines N, Rousson V, et al. Evidence-based value of prophylactic drainage in gastrointestinal surgery: a systematic review and meta-analyses. Ann Surg 2004;240:1074-84; discussion 1084-5. [Crossref] [PubMed]
73. Kaminsky PM, Mezhir JJ. Intraperitoneal drainage after pancreatic resection: a review of the evidence. J Surg Res 2013;184:925-30. [Crossref] [PubMed]
74. Witzigmann H, Diener MK, Kienkötter S, et al. No Need for Routine Drainage After Pancreatic Head Resection: The Dual-Center, Randomized, Controlled PANDRA Trial (ISRCTN04937707). Ann Surg 2016;264:528-37. [Crossref] [PubMed]
75. Miao C, Hu Y, Bai G, et al. Prophylactic abdominal drainage for pancreatic surgery. Cochrane Database Syst Rev 2025;5:CD010583. [PubMed]
76. Wang S, Shi N, You L, et al. Minimally invasive surgical approach versus open procedure for pancreaticoduodenectomy: A systematic review and meta-analysis. Medicine (Baltimore) 2017;96:e8619. [Crossref] [PubMed]
77. Palanivelu C, Senthilnathan P, Sabnis SC, et al. Randomized clinical trial of laparoscopic versus open pancreatoduodenectomy for periampullary tumours. Br J Surg 2017;104:1443-50. [Crossref] [PubMed]
78. Poves I, Burdío F, Morató O, et al. Comparison of Perioperative Outcomes Between Laparoscopic and Open Approach for Pancreatoduodenectomy: The PADULAP Randomized Controlled Trial. Ann Surg 2018;268:731-9. [Crossref] [PubMed]
79. van Hilst J, de Rooij T, Bosscha K, et al. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours (LEOPARD-2): a multicentre, patient-blinded, randomised controlled phase 2/3 trial. Lancet Gastroenterol Hepatol 2019;4:199-207. [Crossref] [PubMed]
80. Zureikat AH, Postlewait LM, Liu Y, et al. A Multi-institutional Comparison of Perioperative Outcomes of Robotic and Open Pancreaticoduodenectomy. Ann Surg 2016;264:640-9. [Crossref] [PubMed]
81. Wang SE, Shyr BU, Chen SC, et al. Comparison between robotic and open pancreaticoduodenectomy with modified Blumgart pancreaticojejunostomy: A propensity score-matched study. Surgery 2018;164:1162-7. [Crossref] [PubMed]
82. Warshaw AL. Distal pancreatectomy with preservation of the spleen. J Hepatobiliary Pancreat Sci 2010;17:808-12. [Crossref] [PubMed]
83. Kimura W, Yano M, Sugawara S, et al. Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein: techniques and its significance. J Hepatobiliary Pancreat Sci 2010;17:813-23. [Crossref] [PubMed]
84. Shi N, Liu SL, Li YT, et al. Splenic Preservation Versus Splenectomy During Distal Pancreatectomy: A Systematic Review and Meta-analysis. Ann Surg Oncol 2016;23:365-74. [Crossref] [PubMed]
85. Granieri S, Bonomi A, Frassini S, et al. Kimura's vs Warshaw's technique for spleen preserving distal pancreatectomy: a systematic review and meta-analysis of high-quality studies. HPB (Oxford) 2023;25:614-24. [Crossref] [PubMed]
86. Miao Y, Lu Z, Yeo CJ, et al. Management of the pancreatic transection plane after left (distal) pancreatectomy: Expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2020;168:72-84. [Crossref] [PubMed]
87. Probst P, Hüttner FJ, Klaiber U, et al. Stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy. Cochrane Database Syst Rev 2015;2015:CD008688. [Crossref] [PubMed]
88. Yamamoto M, Hayashi MS, Nguyen NT, et al. Use of Seamguard to prevent pancreatic leak following distal pancreatectomy. Arch Surg 2009;144:894-9. [Crossref] [PubMed]
89. Kondo N, Uemura K, Nakagawa N, et al. A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial). Ann Surg Oncol 2019;26:1519-27. [Crossref] [PubMed]
90. Merdrignac A, Garnier J, Dokmak S, et al. Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial. Ann Surg 2022;276:769-75. [Crossref] [PubMed]
91. Iannitti DA, Coburn NG, Somberg J, et al. Use of the round ligament of the liver to decrease pancreatic fistulas: a novel technique. J Am Coll Surg 2006;203:857-64. [Crossref] [PubMed]
92. Hassenpflug M, Hinz U, Strobel O, et al. Teres Ligament Patch Reduces Relevant Morbidity After Distal Pancreatectomy (the DISCOVER Randomized Controlled Trial). Ann Surg 2016;264:723-30. [Crossref] [PubMed]
93. Deng Y, He S, Cheng Y, et al. Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. Cochrane Database Syst Rev 2020;3:CD009621. [Crossref] [PubMed]
94. Ratnayake CBB, Wells C, Hammond J, et al. Network meta-analysis comparing techniques and outcomes of stump closure after distal pancreatectomy. Br J Surg 2019;106:1580-9. [Crossref] [PubMed]
95. de Rooij T, van Hilst J, van Santvoort H, et al. Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD): A Multicenter Patient-blinded Randomized Controlled Trial. Ann Surg 2019;269:2-9. [Crossref] [PubMed]
96. Huang B, Feng L, Zhao J. Systematic review and meta-analysis of robotic versus laparoscopic distal pancreatectomy for benign and malignant pancreatic lesions. Surg Endosc 2016;30:4078-85. [Crossref] [PubMed]
97. Xourafas D, Ashley SW, Clancy TE. Comparison of Perioperative Outcomes between Open, Laparoscopic, and Robotic Distal Pancreatectomy: an Analysis of 1815 Patients from the ACS-NSQIP Procedure-Targeted Pancreatectomy Database. J Gastrointest Surg 2017;21:1442-52. [Crossref] [PubMed]
98. Strasberg SM, Drebin JA, Linehan D. Radical antegrade modular pancreatosplenectomy. Surgery 2003;133:521-7. [Crossref] [PubMed]
99. Mitchem JB, Hamilton N, Gao F, et al. Long-term results of resection of adenocarcinoma of the body and tail of the pancreas using radical antegrade modular pancreatosplenectomy procedure. J Am Coll Surg 2012;214:46-52. [Crossref] [PubMed]
100. Cao F, Li J, Li A, et al. Radical antegrade modular pancreatosplenectomy versus standard procedure in the treatment of left-sided pancreatic cancer: A systemic review and meta-analysis. BMC Surg 2017;17:67. [Crossref] [PubMed]
101. Smoot RL, Donohue JH. Modified Appleby procedure for resection of tumors of the pancreatic body and tail with celiac axis involvement. J Gastrointest Surg 2012;16:2167-9. [Crossref] [PubMed]
102. Peters NA, Javed AA, Cameron JL, et al. Modified Appleby Procedure for Pancreatic Adenocarcinoma: Does Improved Neoadjuvant Therapy Warrant Such an Aggressive Approach? Ann Surg Oncol 2016;23:3757-64. [Crossref] [PubMed]
103. Cesaretti M, Abdel-Rehim M, Barbier L, et al. Modified Appleby procedure for borderline resectable/locally advanced distal pancreatic adenocarcinoma: A major procedure for selected patients. J Visc Surg 2016;153:173-81. [Crossref] [PubMed]
104. Latona JA, Lamb KM, Pucci MJ, et al. Modified Appleby Procedure with Arterial Reconstruction for Locally Advanced Pancreatic Adenocarcinoma: A Literature Review and Report of Three Unusual Cases. J Gastrointest Surg 2016;20:300-6. [Crossref] [PubMed]
105. Liu L, Liu TX, Huang WX, et al. Distal pancreatectomy with En bloc celiac axis resection for locally advanced pancreatic body/tail cancer: A systematic review and meta-analysis. Asian J Surg 2022;45:51-61. [Crossref] [PubMed]
106. Yamaguchi K, Konomi H, Kobayashi K, et al. Total pancreatectomy for intraductal papillary-mucinous tumor of the pancreas: reappraisal of total pancreatectomy. Hepatogastroenterology 2005;52:1585-90. [PubMed]
107. Almond M, Roberts KJ, Hodson J, et al. Changing indications for a total pancreatectomy: perspectives over a quarter of a century. HPB (Oxford) 2015;17:416-21. [Crossref] [PubMed]
108. Reddy S, Wolfgang CL, Cameron JL, et al. Total pancreatectomy for pancreatic adenocarcinoma: evaluation of morbidity and long-term survival. Ann Surg 2009;250:282-7. [Crossref] [PubMed]
109. Petrucciani N, Nigri G, Giannini G, et al. Total Pancreatectomy for Pancreatic Carcinoma: When, Why, and What Are the Outcomes? Results of a Systematic Review. Pancreas 2020;49:175-80. [Crossref] [PubMed]
110. Barbier L, Jamal W, Dokmak S, et al. Impact of total pancreatectomy: short- and long-term assessment. HPB (Oxford) 2013;15:882-92. [Crossref] [PubMed]
111. Jethwa P, Sodergren M, Lala A, et al. Diabetic control after total pancreatectomy. Dig Liver Dis 2006;38:415-9. [Crossref] [PubMed]
112. Roberts KJ, Blanco G, Webber J, et al. How severe is diabetes after total pancreatectomy? A case-matched analysis. HPB (Oxford) 2014;16:814-21. [Crossref] [PubMed]
113. Gubergrits N, Malecka-Panas E, Lehman GA, et al. A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery. Aliment Pharmacol Ther 2011;33:1152-61. [Crossref] [PubMed]
114. Gajewska-Naryniecka A, Szwedowicz U, Łapińska Z, et al. Irreversible Electroporation in Pancreatic Cancer-An Evolving Experimental and Clinical Method. Int J Mol Sci 2023;24:4381. [Crossref] [PubMed]
115. Martin RC 2nd, Kwon D, Chalikonda S, et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg 2015;262:486-94; discussion 492-4. [Crossref] [PubMed]
116. Scheffer HJ, Vroomen LG, de Jong MC, et al. Ablation of Locally Advanced Pancreatic Cancer with Percutaneous Irreversible Electroporation: Results of the Phase I/II PANFIRE Study. Radiology 2017;282:585-97. [Crossref] [PubMed]
117. Cipora E, Czerw A, Partyka O, et al. Quality of Life in Patients with Pancreatic Cancer-A Literature Review. Int J Environ Res Public Health 2023;20:4895. [Crossref] [PubMed]
118. Pandya GJ, Shelat VG. Radiofrequency ablation of pancreatic ductal adenocarcinoma: The past, the present and the future. World J Gastrointest Oncol 2015;7:6-11. [Crossref] [PubMed]
119. Park DH, Choi JH, Oh D, et al. Endoscopic ultrasonography-guided ethanol ablation for small pancreatic neuroendocrine tumors: results of a pilot study. Clin Endosc 2015;48:158-64. [Crossref] [PubMed]
120. Song TJ, Seo DW, Lakhtakia S, et al. Initial experience of EUS-guided radiofrequency ablation of unresectable pancreatic cancer. Gastrointest Endosc 2016;83:440-3. [Crossref] [PubMed]
121. Yousaf MN, Ehsan H, Muneeb A, et al. Role of Radiofrequency Ablation in the Management of Unresectable Pancreatic Cancer. Front Med (Lausanne) 2020;7:624997. [Crossref] [PubMed]