Perioperative management - Central liver resection (mesohepatectomy) for Klatskin tumor

Perihilar/central bile duct carcinoma (Klatskin tumor) originates from the bifurcation of the extrahepatic bile ducts. Due to the almost absent muscular layer of the bile ducts, there is early invasion into the liver parenchyma or the portal vein.

The only curative treatment option is radical R0 resection, which can only be achieved through an en bloc resection of the bile ducts, bile duct bifurcation with liver resection. The assessment of resectability and development of an appropriate resection strategy is of utmost importance due to the close anatomical relationship to the portal vein bifurcation and the hepatic arteries.

Curative approaches in advanced stages are regularly associated with significant loss of liver parenchyma and pose a challenge for surgery, anesthesia, and intensive care medicine.

An isolated resection of the extrahepatic bile duct system (so-called "isolated hilus resection") cannot be considered a curative procedure. The result is local recurrence rates of 70-90% and virtually no long-term survival. The bile ducts of the caudate lobe (Segment 1), which regularly open near the bile duct bifurcation, are predisposed to local recurrences.

To achieve an adequate safety margin, a simultaneous en bloc resection of the central liver parts together with the bile duct system is always necessary. This includes the caudate lobe as well as the hilar portions of segments 4, 5, and 8. Achieving a proximal and lateral safety margin is often problematic due to the usually diffuse infiltration along the bile ducts and perineural sheaths.

Extended hemihepatectomies have been established as standard procedures, with right-sided procedures requiring the so-called hilar en bloc resection including the portal vein bifurcation. In left-sided procedures, due to the course of the right hepatic artery, dissection is usually required dorsal to the bile duct, so a general portal vein resection is not indicated here.

In an inoperable situation due to technical reasons or functional irresectability, liver transplantation is an option, although with poor results so far and a glaring shortage of organs. Improved results are available for selected patients in a multimodal treatment program.

For these extensive liver resections of an organ damaged by cholestasis and bile duct inflammation, preoperative assessment of residual liver function is essential. Conditioning of the liver through selective bile duct drainage and, before extensive right resections, through hypertrophy induction (portal vein embolization/ALPPS) is an option for improved outcomes.

Especially when hypertrophy induction is not possible, the procedure described here of central liver resection is a technical variant for radical resection while simultaneously maximizing the preservation of healthy liver parenchyma.

In the demonstrated case, it is a stenosing bile duct tumor at the hepatic bifurcation Bismuth IIIb, diagnosed by MRCP, ERCP, and brush cytology. An extended right resection was not feasible due to atrophy of the left liver lobe. Therefore, removal of liver segments 1, 4, 5, and 8 was performed while preserving the lateral segments 6, 7, and 2, 3, particularly since the portal vein bifurcation and the left hepatic artery did not appear infiltrated morphologically.

Non-resectability of hilar cholangiocarcinoma:

• Encasement/occlusion of the portal vein
• Lymph node metastases beyond the hepatoduodenal ligament
• Distant metastases
• Malignant ascites
• Advanced liver diseases, particularly advanced PSC (primary sclerosing cholangitis)
• Tumors that have reached the segmental bile ducts on both sides simultaneously.
• Tumors infiltrating both hepatic arteries.

Liver cirrhosis:

• Assessing the functional reserve of a cirrhotic liver is challenging. Besides the general physical condition and the Child-Pugh score, the severity of portal hypertension is crucial. The most important parameters for adequate postoperative liver function are normal bilirubin levels and a hepatic venous pressure gradient of < 10 mmHg. Indicators of the extent of portal hypertension include spleen size, the presence of esophageal varices, and platelet count (Caution: < 100,000/μl).
• Significantly increased risk with portal hypertension due to complicated, risky dissection in the liver hilum.

Insufficient residual liver volume:

The most important cause of perioperative mortality after liver resection is liver failure. Risk evaluation is therefore of crucial importance, as therapeutic options for postoperative liver insufficiency are very limited.

• For Klatskin tumors, a residual liver volume of 40% should be aimed for, as the liver is pre-damaged by cholestasis.
• Evaluation of hypertrophy conditioning via portal vein embolization (PVE) or ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy).
• Corresponding hypertrophy is expected after 3 to 5 weeks, but can take significantly longer in a cholestatic or cirrhotic liver.

General inoperability:

Underlying conditions of the patient, particularly cardiac risks, must be considered.

History: Risk factors include recurrent cholangitis, primary PSC, and bile duct cysts.

Clinical signs: painless jaundice (itching skin, discolored stool), pain, weight loss, fever

Tumor markers: Ca19-9, CEA

Imaging:

The following diagnostic algorithm is recommended:

1. (Contrast-enhanced)ultrasound as basic diagnostics

2. Contrast-enhancedCT of the abdomen

The standard procedure for surgical planning and clarification of resectability is multiphase contrast-enhanced rapid spiral computed tomography with thin slices. This achieves high-resolution imaging of the arterial, portal venous, and venous structures. With appropriate evaluation software, tumor volume, total liver volume, and remaining liver volume after resection can be estimated. Regarding liver function, the CT provides only indirect indications: enlarged spleen, recanalized umbilical vein, prominent caudate lobe, dilated bile ducts. A disadvantage is inadequate visualization of the bile duct system.

3. MRI/MRCP

Before interventional procedures as a non-invasive method for imaging the bile duct system, to assess bile duct conditions without an influencing post-interventional inflammatory reaction. Detached liver segments can also be depicted.

4. ERCP and/or PTCD possibly with cholangioscopy

During ERCP, there is the possibility of histological and cytological tissue diagnostics, in specific cases also via EUS-guided fine needle aspiration. ERCP combines diagnostic and therapeutic options in biliary obstruction.

Tissue sampling is performed in the form of brush cytology and direct forceps biopsy, with the combination of both methods increasing sensitivity.

A modern cytological method using aspirated bile is FISH (Fluorescence in situ Hybridization) with detection of chromosomal aberrations of the bile duct epithelium.

A disadvantage is bacterial contamination up to the intrahepatic bile ducts, increasing the rate of infectious complications and potential tumor cell dissemination (liver metastases, implantations during intraoperative removal of the bile duct stent).

PTCD is usually indicated when ERCP cannot be performed. The advantages of PTCD are more accurate and easily reproducible cholangiography with minimal contamination risk.

5. Optional staging laparoscopy to exclude liver metastases and/or peritoneal carcinomatosis.

PET-CT (Positron Emission Tomography combined with CT) 

Not the first choice in initial diagnostics, as it is inferior to other imaging methods.

A reasonable indication seems to be the detection of local recurrences after resection of hilar cholangiocarcinomas.

Endosonography

Endoscopic ultrasound offers high-resolution imaging of structures adjacent to the stomach and duodenum. This includes the common hepatic duct up to the liver hilum, local lymph nodes, and adjacent vessels. Tissue acquisition is possible via fine needle aspiration (FNA), with sensitivity lower than ERC-based tissue acquisition methods.

Remark:

Histological or cytological confirmation of malignancy is only possible in a few cases due to difficult visualization. If there is sufficient clinical suspicion, surgery is indicated even without prior histological confirmation.

The extent of the tumor disease is ultimately only visible intraoperatively; only then can resectability be determined. Thus, a high exploration rate must be accepted.

• Endoscopic drainage before resection:
  • Stents should generally be avoided. However, liver dysfunction increases under cholestasis, which is responsible for increased morbidity and mortality. Therefore, stents are often unavoidable.
  • Before stent placement, the necessary imaging to clarify resectability should be completed. An existing stent also complicates the intraoperative assessment of resectability.
  • Indications: Presence of cholangitis or significant cholestasis, bilirubin level >10 mg/dl, possibly bilateral drainage.
  • In contrast to distal bile duct carcinomas, preoperative decompression of the bile ducts is recommended for hilar tumors. The placement of a bile duct drainage must ultimately be decided by the surgeon, as on one hand, the liver parenchyma remaining postoperatively must be decompressed preoperatively, while on the other hand, cholangiosepsis is one of the main causes of postoperative mortality. After any manipulation of the bile ducts, the risk of bacterial contamination of the bile ducts increases. Therefore, in the case of post-ERCP/stent, antibiotic prophylaxis or therapy before and after liver resection is advised, otherwise single-shot antibiotic is sufficient.
• Blood group determination with sufficient transfusion reserve (4-6 units of packed red blood cells, possibly FFP or platelets)!
• In case of increased cardiopulmonary risk, assessment of surgical risk through further diagnostics (stress ECG, cardiac echo, coronary angiography, lung function test)
• Adequate intensive care capacity for high-risk patients
• A mild laxative or enema is recommended the day before.

Standardized consent forms should be used for patient education. These also include appropriate anatomical drawings where findings can be recorded. Alternatives and additional treatment options should be discussed, particularly any extensions of the primary procedure should always be considered.

General Risks

• Bleeding
• Postoperative bleeding
• Hematoma
• Need for transfusions with associated transfusion risks
• Thromboembolism
• Wound infection
• Abscess
• Injury to adjacent organs/structures (stomach, esophagus, spleen, diaphragm)
• Wound dehiscence
• Incisional hernia
• Subsequent surgery
• Mortality

Specific Risks

• Liver parenchyma necrosis
• Bile fistula
• Bilioma
• Hemobilia
• Biliary peritonitis
• Bile duct stricture
• Pleural effusion
• Air embolism (due to accidental or unnoticed opening of hepatic veins)
• Portal vein thrombosis
• Hepatic artery thrombosis
• Chronic liver failure
• Liver failure with hepatic coma
• Tumor recurrence

Intubation anesthesia

Intra- and postoperative analgesia with epidural catheter

Follow this link to PROSPECT (Procedure specific postoperative pain management) or to the current guideline Treatment of acute perioperative and post-traumatic pain

In liver resections, anesthesia plays an important role in intraoperative blood-saving measures.
The pressure in the hepatic sinusoids depends on the pressure in the hepatic veins, which in turn depends on the central venous pressure (CVP). Therefore, during the transection of the liver parenchyma, the CVP should be reduced to 2-5 mmHg, which can significantly reduce intraoperative blood loss and transfusion volume.
In the event of accidental opening of large hepatic veins or the vena cava, the PEEP can be temporarily increased to prevent impending air embolisms.

A positive end-expiratory pressure (PEEP) is a parameter in mechanical ventilation. It refers to a positive pressure in the lungs at the end of expiration. It is generated by a PEEP valve.

Depending on liver function and blood loss, there may be disturbances in the coagulation and fibrinolysis system. This requires close intraoperative monitoring and, if necessary, early substitution of coagulation factors.

Supine position, both arms adducted, slight hyperextension at the thoracolumbar junction

• Surgeon on the right side of the patient
• 1st assistant on the left side of the patient
• 2nd assistant on the right side of the patient, towards the head of the surgeon
• Scrub nurse on the left side of the patient, towards the feet of the 1st assistant

• Gallbladder, Vascular Tray, or LTX Tray
• Pulley Hook System,
• Vessel Loops
• Aids for Parenchymal Resection, here Ultrasonic Aspirator (CUSA®), for more information on aids for parenchymal resection, see

• Ultrasound Device

• Aids for Focal Hemostasis of the Liver: e.g., Clips, Bipolar and Monopolar Coagulation, Argon Beam, Infrared Coagulation, etc.

• Aids for Vascular Sealing at the Resection Surface. In the demonstrated case, a hemostatic powder HaemoCer PLUS is used:
  • This is a ready-to-use powder made from polymerized plant extracts.
  • The product is biocompatible and contains no animal or human components.
  • HaemoCer is applicable for both diffuse and active bleeding.
  • The completely absorbable material accelerates natural blood clotting (hemostasis) due to its extremely high water absorption capacity.
  • There is an accumulation of fibrin, thrombin, and red blood cells at the bleeding source. A natural clot forms, and the bleeding is stopped. After hemostasis is achieved, the wound is surrounded by a stable and firmly adhering gel layer. This serves as an additional barrier to protect against renewed blood leakage.
  • Independent studies also show that the use of plant-based hemostatic powders (polysaccharides) helps reduce postoperative adhesions.
  • The product is manufactured and certified in Germany.
  • Within 48 hours, it is completely broken down by amylase in the body.

Medical Aftercare
Crucial is early postoperative extubation and adequate pain management (epidural analgesia!). Follow the link here to PROSPECT (Procedures Specific Postoperative Pain Management).
Follow the link here to the current guideline: Treatment of acute perioperative and post-traumatic pain.

• perioperative antibiotics 48 – 72h postoperatively
  Start perioperative antibiotics with the induction of anesthesia, e.g., combination of Claforan® 3 × 2 g and Clont® 3 × 0.5 g i.v.; in case of penicillin allergy, use Ciprofloxacin 200mg 1-0-1 instead of Claforan®
• frequent laboratory checks
• Determination of bilirubin from the drainage fluid
• Removal of drains depending on the amount of fluid and the aforementioned values
• PDK removal by anesthesia on the 3rd – 6th postoperative day
• PPI prophylaxis: initially i.v., then orally

Thrombosis Prophylaxis

In the absence of contraindications, due to the high risk of thromboembolism, low molecular weight heparin should be administered prophylactically, possibly in a weight- or risk-adapted dosage. Note: kidney function, HIT II (history, platelet control). Follow the link here to the current guideline Prophylaxis of venous thromboembolism (VTE).

Mobilization
As early as possible, especially for pneumonia prophylaxis, which is essential in any liver resection. Gradual resumption of physical activity until full load.

Physical and Respiratory Therapy
Pneumonia prophylaxis is vital and takes absolute priority in liver resections! For example, breathing assistant (Bird) and/or Triflow exercise device and appropriate physical therapy.

Dietary Progression
Rapid dietary progression; on the 1st postoperative day, tea, soup, rusks.

Bowel Regulation
From the 3rd day, the patient should be relieved, which can be stimulated with an enema, for example.

Incapacity for Work
In open procedures with median laparotomy extension into the right flank, the risk of postoperative incisional hernia is not insignificant, so the patient should adhere to postoperative rest for at least four to six weeks. Light work, especially office tasks, can be resumed earlier.