Perioperative management - Pylorus-preserving pancreaticoduodenectomy, according to Longmire-Traverso, robotically assisted

Fundamentals:

• The pylorus-preserving pancreatic head resection according to Traverso-Longmire is considered the current standard for malignant tumors of the pancreatic head.
• Despite the overall poor prognosis of these tumors, the surgery represents the only potentially curative procedure.
• In principle, the indication for pancreatic head resection exists for histologically confirmed malignancies and when there is sufficient suspicion of malignancy, provided that pre- and intraoperatively there is at least the prospect of resecting the tumor in toto, and the patient is in a general sufficient condition for this procedure.

Main Indication:

• The most common malignant tumor of the pancreas is ductal adenocarcinoma (85%), with the pancreatic head being affected in 65% of cases.

Other Indications:

• distal bile duct carcinoma
• ampullary carcinoma
• duodenal carcinoma
• large adenomas of the ampulla or near the ampulla in the duodenum
• benign/cystic tumors of the pancreatic head
• intraductal papillary mucinous neoplasm (IPMN) of the main and side ducts (with "high-risk stigmata") as well as the mixed type
• mucinous cystic neoplasm (MCN)
• solid-pseudopapillary neoplasm (SPN)
• chronic pancreatitis with complications, especially with distal bile duct stenosis
• so-called "dilemma" cases (when imaging and clinical presentation cannot reliably differentiate between inflammatory and malignant pancreatic head tumors)
• hereditary gastrinomas in MEN-1 disease (multiple duodenal gastrinomas)
• metastases in the pancreatic head
• pancreas divisum
• rare other pancreatic head tumors

The essential difference to the classical Kausch-Whipple operation is:

• Preservation of the pylorus of the stomach with its neurovascular supply
• In terms of mortality, morbidity, and oncological radicality, there is no difference
• Limiting for an R0 resection is not the gastric margin but the dorsal, retroperitoneal pancreas margin.

Potential advantages of the pylorus-preserving method are:

• a shorter operation time
• less blood loss
• Preservation of physiological gastric emptying: better function regarding absorption, food utilization, and postoperative weight gain

Specific considerations for indication:

Surgical Procedure and Extent of Resection:

-Operative approach dependent on:

• Tumor location
• Stage and classification
• pylorus-preserving vs. "classical" resection (house standard: Traverso-Longmire!)

Resectability Criteria:

From N1 or T3, perioperative chemotherapy is usually performed. Tumor conference! Borderline tumors

Locally limited pancreatic carcinoma or IPMN of the pancreatic head:

-pylorus-preserving pancreatic head resection according to Traverso-Longmire

- In case of R0 resection, adjuvant chemotherapy 4-12 weeks after surgery

- In case of R1, possibly radiochemotherapy

Locally advanced pancreatic carcinoma:

• Infiltration of the A. hepatica com. or the trunk (up to 180°): Borderline resectable: Neoadjuvant + exploration
• Resection not possible → (Radio-) Chemotherapy

Venous infiltration:

• In the case of infiltration of large veins (superior mesenteric vein, splenic vein, or portal vein), resection should be pursued if necessary with vascular reconstruction, as preoperative diagnostics usually cannot differentiate between inflammatory adhesion and tumor infiltration.
• Patients seem to benefit from vascular resection if an R0 resection is successful.

Arterial infiltration:

• The resection and reconstruction of visceral arteries is a case-by-case decision to achieve an R0 resection given the currently insufficient study situation.

Preoperative bile duct drainage:

• The indication for resection is made by the surgeon promptly after diagnosis, especially if it is a potentially resectable finding in jaundiced patients.
• Only in patients with manifest secondary complications of jaundice (deranged plasma coagulation, liver synthesis disorder, reduced cellular defense, purulent cholangitis) should preoperative endoscopic bile duct drainage be considered to gain time and create a better starting situation for the operation.
• In all other cases, preoperative bile duct drainage, whether TPCD (transpapillary) or PTCD (percutaneous-transhepatic), is avoided due to increased postoperative morbidity.

Age and comorbidity:

• Comorbidity is another essential factor in the indication setting.
• Patients with severe cardiovascular comorbidities carry a significantly increased surgical risk.
• High age per se is no longer a contraindication for pancreatic head resection today.

Lymphadenectomy:

• Lymphadenectomy includes the regional lymph nodes at the duodenum and pancreatic head.
• An extension beyond this does not lead to an improvement in survival. Therefore, extended lymph node dissection is controversial due to an increased complication rate.
• Vascular skeletonization along the aorta and superior mesenteric artery with removal of nerve tissue can result in persistent gastric emptying disorders and severe diarrhea with malnutrition.

Indication for Robotic PPPD:

• Preoperative assessment of resectability is not always exact, as cross-sectional imaging is not one hundred percent reliable here.
• Even in open exploration, it is a challenge to correctly assess arterial infiltration.
• Especially in the early days of implementing robotic pancreatic head resection, the indication for robotic approach is seen in small tumors that have a good safety distance from the upper abdominal arteries and portal venous branches. If intraoperatively there is indeed a vascular infiltration, a conversion to an open approach should currently be performed. (Note: This approach is certainly in progress, and advances in robotics are also to be expected in the near future.)

Currently, resectability is assessed according to the so-called ABC criteria of resectability according to the International Association of Pancreatology (IAP) consensus:

According to: Isaji, S., et al., International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology, 2018. 18(1): p. 2-11.

Alternative Procedures:

Regarding Access Route

• Open PPPD
• Laparoscopic PPPD

Regarding Extent of Surgery

• Classical Whipple with distal gastric resection
• Left pancreatic resection for tumor location in the body or tail
• Total pancreatectomy for infiltration of the entire pancreas

surgical-technical:

• Portal vein occlusion with pronounced collateral circulation
• Spleen vein occlusion with pronounced collaterals and presence of gastric varices

tumor-related unresectability:

• Tumor infiltration of supplying arteries of the liver (hepatic artery), inferior vena cava, aorta, small intestine (superior mesenteric artery, > 180°), celiac trunk (> 180°)
• Peritoneal carcinomatosis
• Liver metastases primarily from ductal pancreatic carcinoma (exceptions: oligometastasis within the framework of multimodal therapy concepts in studies)

tumor-related contraindications for primary surgical approach:

• Superior mesenteric artery contact > 180°
• Celiac trunk contact > 180°
• Infiltration of the common hepatic artery with contact to the proper hepatic artery or celiac trunk
• Infiltration of the superior mesenteric vein/portal vein and their tributaries without possibility of reconstruction
• For a CA 19-9 > 500 U/ml, a diagnostic laparoscopy should be performed to assess peritoneal carcinomatosis. Subsequently, after exclusion, a neoadjuvant concept can be pursued.

Note: The tumor-related contraindications listed last regarding the infiltration of the common hepatic artery, superior mesenteric artery apply primarily to the primary operation, as in individual cases after neoadjuvant (radio-)chemotherapy, even oligometastatic or arterially infiltrating tumors can be resected R0.

• The infiltration of the pylorus or distal stomach is a contraindication, as in these cases a classic pancreatic head resection according to Kausch-Whipple should be performed.
• In the case of continuous involvement of the pancreatic tail, a pancreatectomy is performed to ensure an R0 resection

patient-specific:

• acute florid pancreatitis
• liver cirrhosis Child B and C
• poor heart and lung function (NYHA status and GOLD status)
• ECOG status ≥ 2
• high-grade carotid stenoses before therapy

Note: the absolute age is no longer relevant, but rather the clinical condition of the patient (ECOG status, etc.)

(Relative) contraindications for a robotic approach (currently)

• Small/no safety margin to the upper abdominal arteries and portal venous branches
• Large space-occupying lesions over 5 cm
• accompanying pancreatitis

Currently, resectability is comprehensively assessed according to the so-called ABC criteria of resectability according to the International Association of Pancreatology (IAP) consensus:

According to: Isaji, S., et al., International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology, 2018. 18(1): p. 2-11.

History/Clinical Findings:

• no characteristic leading symptom, nonspecific with loss of appetite, feeling of fullness, digestive disorders, fatty stools, weight loss, B symptoms
• Jaundice
• New onset diabetes mellitus
• Upper abdominal and back pain
• obstructive pancreatitis
• palpable tumor
• Previous surgeries
• Cholestasis, cholangitis, Courvoisier's sign (palpable enlarged tense elastic gallbladder)

Laboratory Diagnostics

• CBC, electrolytes, CRP, cholestasis markers, liver synthesis markers, kidney markers, albumin, lipase/amylase, blood glucose, OGTT (oral glucose tolerance test) or HbA1c, blood type, coagulation, 2-4 RBC units as per surgeon's discretion
• Tumor marker CA 19-9 (independent predictor of poorer overall survival)
• CEA (also and especially from endosonographically obtained cyst punctate)
• Genetics: PRSS1, SPINK1, PSTI, CFTR (in young patients to exclude hereditary genesis – strict indication due to high cost!)
• Hormone analysis if endocrine active neoplasms are suspected

Note: Pancreatic function diagnostics can use the following tests:

• Oral glucose tolerance test in previously unknown diabetes mellitus to assess endocrine pancreatic function
• HbA1c to assess endocrine pancreatic function
• Stool elastase for diagnosing exocrine pancreatic function

Imaging Diagnostics

• Transcutaneous Sonography: Basic diagnostics with good and non-invasive visualization of the pancreatic parenchyma, also allows detection of pancreatic duct dilation. Additional assessment of the portal vein system through color Doppler sonography. Ultrasound contrast agents can aid in differential diagnosis between inflammatory and tumorous, cystic tumor and pseudocyst. Furthermore, detection of cholestasis, cholecystolithiasis, liver metastases, ascites.
• CT Abdomen: For solid changes, a multiphase CT of the abdomen is best suited. CT can generally assess pancreatic masses, lymph node enlargements, perfusion of the superior mesenteric vein, portal vein, superior mesenteric artery, and celiac trunk, distant metastases, pancreatic calcifications, pancreaticolithiasis, distant metastasis
• CT Thorax: to exclude pulmonary metastasis
• MRI with MRCP (Magnetic Resonance Cholangiopancreatography): Non-invasive visualization of the bile and pancreatic duct systems. More sensitive than ERCP in detecting solid wall changes (so-called "mural nodules"). For cystic tumors, an MRI of the upper abdomen with MRCP is recommended, which is superior to CT in diagnostic potency. Additionally, MRI with MRCP better visualizes the spatial relationships between the tumor and pancreatic duct system. Furthermore, duct irregularities, stenoses, dilations, double-duct sign = simultaneous stenosis of the pancreatic duct and common bile duct, CBD stenosis, dilation, and pancreaticolithiasis can be detected.
• MRI with liver-specific contrast agent: Exclusion of hepatic metastasis
• Possibly CEUS ultrasound (contrast-enhanced ultrasound) for assessing liver lesions
• Possibly FDG-PET-CT: in suspected metastatic situation

Note: Visualization of the bile or pancreatic duct systems is only required in unclear cases. ERCP and MRCP are suitable for this. The "double-duct sign" (simultaneous stenosis/interruption of the pancreatic duct and common bile duct) is considered pathognomonic for carcinoma.

Endoscopic/Invasive Diagnostics

• Possibly EGD: histological confirmation possible in papillary carcinoma, exclusion or extent of duodenal polyps with stomach preservation, transpapillary secretion of viscous mucus highly suspicious for IPMN

Note: A histological confirmation of the tumor is not required preoperatively if there is sufficient suspicion of a tumor, but it is necessary before initiating neoadjuvant (radio)chemotherapy or palliative chemotherapy in the metastatic stage.

• Possibly Endosonography (EUS): clarification of gastric collateral pathologies and further depiction of the pancreas by endosonography to assess mural changes in cystic neoplasms for type diagnosis of these changes and for cyst puncture or biopsy confirmation, examiner-dependent, additionally: determination of local tumor extent and assessment of local lymph nodes (lymph nodes > 1 cm are suspicious for malignancy), possibly with puncture (fine needle aspiration of cyst fluid) and biopsy.
• Possibly Laparoscopy in suspected peritoneal carcinomatosis/CA 19-9 > 500 U/ml and/or proven ascites -> puncture with cytology
• ERCP: Due to possible complications (pancreatitis, bleeding, perforation), preferably only for therapeutic intervention, otherwise MRCP or EUS; interventional relief of the bile duct system only in unresectability or delay of surgery, otherwise immediate surgical intervention

Preoperative Functional Diagnostics

• depending on pre-existing conditions: ECG, echocardiogram, lung function

Special Preparation

• Blood group determination
• Provision of 2-4 cross-matched erythrocyte concentrates as per the surgeon's discretion
• Pyloric stenosis: preoperative gastric tube
• If necessary, stabilization of coagulation (e.g., Konakion® for 2-3 days preoperatively) in jaundiced patients.
• If necessary, improvement of liver function (e.g., DHC stenting): Only in patients with manifest secondary complications of jaundice (deranged plasma coagulation, liver synthesis disorder, reduced cellular defense), bilirubin >15 mg/dl, or in postponed surgery and jaundice

Preoperative Preparation

• Body care: shower the evening before
• Shaving: from the jugulum to the symphysis; legs in case of vein harvesting for vascular construction
• Preoperative nutrition: Eat lunch the day before, then small intestine absorbable diet (SAD), in case of reduced general condition and nutritional status (albumin < 30mg/dL) additionally high-calorie nutrition (3 days preoperatively), human albumin, iron (Ferrinject), vitamin B12, folic acid
• Thrombosis prophylaxis: See guideline Prophylaxis of venous thromboembolism (VTE)
• Premedication: Epidural catheter. Admission to intensive care unit. Central venous catheter
• Antibiotics: according to house standard, e.g., Cefuroxime 1.5g and Clont 500 mg or Rocephin (Ceftriaxone) 2g + Clont 500mg (repeat after 3 hours of surgery time)
• If necessary: Octreotide: (somatostatin analogue) 100 µg subcutaneously (2 ampoules) to be taken to the operating room, every 8 hours for 24 hours in case of oral fasting

Significant intervention, therefore pay special attention to the informed consent period (> 24h; better to inform during the initial consultation). Always with a drawing to illustrate the postoperative anatomy! 

General Complications

• Wound healing disorder
• Thromboembolism
• Pneumonia
• Lymphatic fistula
• Injury to adjacent structures (intestine, vessels, nerves, other organs)
• Extension of the operation at the surgeon's discretion
• Follow-up interventions
• Long-term intensive medical treatment in case of complications
• Bleeding/rebleeding, PPH = postpancreatectomy hemorrhage
• Allogeneic blood transfusions

Specific Complications

• Pancreatic fistula POPF = postoperative pancreatic fistula
• Gastric emptying disorder
• Bile leakage/bilioma
• Anastomotic insufficiency/stenosis
• Necrosis of the pancreatic remnant
• Endocrine and exocrine pancreatic insufficiency, possibly associated dietary changes
• Insulin-dependent diabetes mellitus (lifelong)
• Peptic ulcers of the jejunum
• Episodes of cholangitis with biliodigestive anastomosis
• Extension of the procedure up to pancreatomy +/- splenectomy

Note: Definition and classification of PPH, POPF, and DGE by the International Study Group of Pancreatic Surgery (ISGPS)