Expert Consensus on Laparoscopic Radical Resection of Gallbladder Cancer (2023)

Authors: Biliary Surgery Group of the Chinese Society of Surgery, Biliary Surgery Expert Working Group of the Surgeon Branch of the Chinese Medical Doctor Association

Source: Chinese Journal of Surgery, 2024, 62(4)

summary

In recent years, the incidence of gallbladder cancer has been increasing. Radical surgery remains the most promising cure for patients with gallbladder cancer. At present, although the techniques required for laparoscopic radical cholecystectomy have become more and more mature, and the reports are increasing, there is still some controversy in the laparoscopic treatment of gallbladder cancer. In order to standardize the development of laparoscopic radical cholecystectomy, the Biliary Surgery Group of the Surgical Branch of the Chinese Medical Association and the Biliary Surgery Expert Working Group of the Surgeon Branch of the Chinese Medical Doctor Association organized a discussion and formulated the relevant suggestions on the operation process of laparoscopic radical cholecystectomy, and put forward suggestions from many aspects such as safety, preoperative evaluation, indications, surgical team, patient position layout, intraoperative frozen pathology, lymph node dissection, liver resection, bile duct resection, etc. Suggestions on the operation process and precautions are also put forward, which provide guidance for the standardized development of laparoscopic radical cholecystectomy.

Gallbladder cancer refers to malignant tumors that originate in the gallbladder, including the base of the gallbladder, body, neck, and cystic duct [1]. Although laparoscopic surgery has been widely used in the surgical treatment of abdominal tumors such as liver cancer, pancreatic cancer, gastric cancer, and colorectal cancer [2, 3], there is still some controversy in the laparoscopic surgical treatment of gallbladder cancer, and the main controversies are whether laparoscopic surgery can achieve an R0 resection rate similar to that of open surgery, whether it can obtain an adequate number of lymph node dissections, whether it increases the risk of intra-abdominal tumor dissemination, and whether it can achieve short-term and long-term efficacy comparable to that of open surgery [4]. At present, the main technologies involved in laparoscopic radical resection of gallbladder cancer (LRRGC) are very mature, and the number of cases reported in the literature is increasing, but there is no relevant operation procedure and expert consensus in mainland China. In order to standardize the clinical diagnosis and treatment of LRRGC, the Biliary Surgery Group of the Chinese Society of Surgery and the Biliary Surgery Expert Working Group of the Surgeon Branch of the Chinese Medical Doctor Association discussed the current application status and safety of LRRGC, formulated relevant indications, precautions and guiding suggestions on the operation process, and gave clinical guidance and suggestions on the treatment principles and precautions for reradical resection of gallbladder cancer (gallbladder cancer found by postoperative pathological examination) for delayed diagnosis.

Consensus target population

This consensus applies to adult (age ≥ 18 years) patients undergoing radical resection of gallbladder cancer.

Who uses consensus

Clinicians, nurses, and technicians engaged in biliary tract diseases in medical institutions at all levels, as well as personnel engaged in related teaching and scientific research.

Search strategy

A literature search was conducted to address the clinical question of whether patients with gallbladder cancer are suitable for laparoscopic radical resection until June 2023. A total of 6 002 articles were retrieved using gallbladder carcinoma, laparoscopic, and minimally invasive (minimally invasive) as search keywords, and comprehensive data such as PubMed, Medline, Embase, and Cochrane systematic review databases were searched, and a total of 6 002 articles were retrieved. A total of 102 clinically relevant papers were obtained.

Descriptions of testimonials and reviews

The recommendations were all based on the Delphi method to form a recommendation grade. At the same time, the degree of acceptance of each recommendation by the experts of the working group was quantified through a "9-point Likert scale" (1 point is the lowest, 9 points are the highest). The strength of consensus is divided into strong (>80% of the votes ≥7 points), conditional (65%~80% of the votes≥7 points), and weak (<65% of the votes≥7 points).

Consensus body

1. Evaluation of the safety and efficacy of LRRGC

Early literature reported that the high rate of puncture hole metastasis and abdominal metastasis after LRRGC was mainly related to intraoperative gallbladder rupture and bile contamination of the abdominal cavity [5, 6]. Recent studies have shown that standardized intraoperative procedures, avoidance of gallbladder rupture, and routine use of pick-up bags can reduce the incidence of puncture holes and abdominal metastases [5,7]. Theoretically, all laparoscopic malignant tumor surgeries have to face the "chimney" effect of CO2 pneumoperitoneum and the questioning of the vaporization effect of ultrasound, and a large number of related studies on gastric cancer, colorectal cancer, liver cancer, etc., show that CO2 pneumoperitoneum does not increase the risk of tumor abdominal metastasis, and the safety and oncological outcomes of laparoscopic and open surgery are similar. However, whether gallbladder cancer with a high degree of malignancy and obvious metastatic characteristics is suitable for laparoscopic radical resection still needs to be clarified by multicenter case studies. LRRGC with less stringent indication selection and non-standard operation procedures has the possibility of tumor dissemination.

Although there are multiple routes of invasion and metastasis of gallbladder cancer, not all patients with gallbladder cancer have a poor prognosis, and the overall survival rate of patients with Tis and T1a gallbladder cancer can reach 100% at 5 years after surgery [8], the overall survival rate of patients with T1b gallbladder cancer can reach 87.52% after surgery [9], and the 5-year overall survival rate of liver tumors and 64.7%~96.0% for abdominal tumors in T2 gallbladder cancer is 42.6%~80.7% and 64.7%~96.0% for abdominal tumors [10, 11]. It can be seen that the biological characteristics and prognosis of gallbladder cancer at stage T2 and below are relatively good, and the invasive and metastatic characteristics are not prominent, which may be more suitable for laparoscopic radical resection. In recent years, with the development of laparoscopic technology, more and more large medical centers at home and abroad have carried out LRRGC. The results of AlMasri et al. [12] (n=680) showed that the overall survival rate at 1, 3 and 5 years after laparoscopic radical resection for T1b~T3 gallbladder cancer was similar to that of open surgery, and there was no difference in the R0 resection rate and the number of lymph node dissections between the two groups, while Zhao et al. [13] (n=1 217), Nakanishi et al. [14] (n=1 792), and Ahmed et al. [15] (n=4 988) had a positive effect on T1~The results of systematic analysis of large cases of patients with stage T3 showed that the laparoscopic group had less intraoperative blood loss, shorter postoperative hospital stay, and the survival rate was similar to that of open surgery. These results suggest that patients with T1b, T2, and some T3 gallbladder cancer may benefit from laparoscopic radical resection. In the case of strict case screening, LRRGC can achieve short-term and long-term efficacy comparable to open surgery, but it still needs to be further validated by large cases and multicenter studies.

2. Standardized operation process and technical points of LRRGC

LRRGC should follow the basic principles of open radical resection. The aim of LRRGC is to achieve a survival benefit consistent with open surgery on the basis of accelerated recovery surgery. Therefore, it is necessary to establish a homogeneous operation process, and carry out strict quality control from the three dimensions of preoperative, intraoperative and postoperative, so as to guide the standardized and orderly development of LRRGC.

(1) Preoperative assessment and indications

The preoperative evaluation of LRRGC is consistent with open surgery and can be found in the Guidelines for the Diagnosis and Treatment of Gallbladder Cancer (2019 Edition) [16]. Attention should be paid to the rigorous selection of patients undergoing LRRGC in combination with preoperative CT and magnetic resonance cholangiopancreatography (MRCP) [17, 18, 19]. Combined with the current reports of LRRGC related literature, mainly focusing on patients with T1b, T2 and some T3 stages, the indications for LRRGC at this stage are mainly defined as patients with T1b stage (clear intraoperative frozen pathological examination) and T2 stage patients without obvious hepatoduodenal ligament lymph node metastasis. Advanced gallbladder cancer has a high incidence of peritoneal metastasis, liver metastasis and invasion of surrounding organs, and open radical resection is still the preferred operation for advanced gallbladder cancer, and the surgical operation is relatively complex. Although some literature reports that the short-term and long-term efficacy of LRRGC for T3 gallbladder cancer is no less than that of open surgery, and for some T3 patients (tumor invasion of liver depth< 2 cm, However, considering the biological characteristics and surgical complexity of T3 gallbladder cancer, it is still necessary to choose carefully, and it is recommended that immature centers choose open radical resection to ensure the perioperative safety and long-term efficacy of patients.

Recommendation 1: For patients with gallbladder cancer or suspected gallbladder cancer, the preoperative management principles refer to the recommendations in the Guidelines for the Diagnosis and Treatment of Gallbladder Cancer (2019 Edition), and it is recommended to routinely undergo full-abdominal contrast-enhanced CT and chest CT examination, and a combination of contrast-enhanced ultrasound, MRCP, three-dimensional visualization technology and PET-CT can be considered for comprehensive evaluation, and a surgical plan should be formulated after excluding metastasis (recommended strength: strong; consistency strength: strong; α score: 95.0%).

Recommendation 2: Open surgery is the preferred surgical modality for advanced gallbladder cancer. Patients with T1b and T2 stages without significant hepatoduodenal ligament lymph node metastases can undergo LRRGC at centers experienced in laparoscopic surgery (recommended intensity: moderate; consistency intensity: conditional; α score: 65.0%).

(2) Surgical team qualifications and learning curve

The team carrying out LRRGC should have the surgical conditions for routine laparoscopic-assisted hepatectomy and laparoscopic-assisted pancreaticoduodenectomy, be proficient in laparoscopic-assisted hepatectomy, lymph node dissection and gastrointestinal reconstruction, and have rich experience in radical open cholecystectomy.

Recommendation 3: Establish a fixed surgical team, the surgical team should have experience in routine laparoscopic-assisted liver resection and lymph node dissection, and have rich experience in radical open gallbladder cancer surgery, and it is recommended to gradually expand the indications according to the learning curve from easy to difficult in the initial stage (recommended strength: strong; consistency strength: conditional; α score: 75.0%).

(3) Patient position, foramen and abdominal cavity exploration

The patient is placed in a supine position with head high and feet low and slightly left tilted, and the leg position is preferred. Depending on the patient's size and the extent of liver resection, an observation hole should be established above or below the umbilicus, and if biliary-intestinal anastomosis is required, it is recommended to have an observation hole under the umbilicus. The auxiliary operation hole is generally centered on the lesion resection area and is distributed in a fan-shaped manner. The general principle is to lay out the operation hole individually according to the operator's habits and preoperative planning. It is necessary to take into account comprehensive factors such as liver resection, lymph node dissection and biliary-intestinal anastomosis to facilitate the operation, and if necessary, add auxiliary operation holes to ensure the smooth operation of the operation.

After the observation hole is established, the abdominal cavity should be fully explored to rule out abdominal metastases that may have been missed by imaging studies. Intraoperative ultrasonography is helpful for detecting intrahepatic metastases and judging the depth of gallbladder cancer invasion of the liver.

Recommendation 4: The operation hole should take into account the operation of liver resection, lymph node dissection and biliary-intestinal anastomosis, which is generally centered on the lesion resection range and has a fan-shaped distribution, which can be determined according to the patient's body shape and preoperative surgical planning (recommended strength: strong; consistency strength: conditional; α score: 70.0%).

Recommendation 5: Careful intraoperative exploration of the abdominal cavity and re-evaluation of the patient in combination with intraoperative ultrasonography can help identify potential liver metastases and guide surgical strategies (recommended intensity: strong; consistency strength: strong; α score: 92.5%).

(4) Standardized intraoperative frozen pathological examination

For cases suspected of gallbladder cancer, cryopathological examination should be performed during the operation, and attention should be paid to standardized surgical operations to avoid gallbladder rupture. The severed end of the cystic duct should be routinely sent for examination, and the use of a pick-up bag should be routinely used, and attention should be paid to a thorough inspection and palpation of the gallbladder specimen, and the gallbladder should be dissected longitudinally from the base of the gallbladder along the hepatic bed-serous junction, and the materials should be taken at multiple points, including the deepest part of the tumor invasion and the junction between the tumor and normal tissue [16,20]. According to the intraoperative freezing results, the diagnosis is definitive, the scope of surgical resection is guided, and attention should be paid to the identification of yellow granulomatous cholecystitis. If there is a high suspicion of tumor invasion of the liver parenchyma before surgery, the removal of the gallbladder alone does not meet the principle of tumor resection and examination, and it is recommended that the gallbladder and the surrounding 2 cm of liver parenchyma be wedge-shaped resection and sent for examination.

Recommendation 6: Pay attention to standardize the process of gallbladder resection and examination, if there is a high suspicion of gallbladder lesions that invade the liver parenchyma, it is necessary to do a whole wedge excision together with the surrounding liver parenchyma for examination, pay attention to avoid gallbladder rupture, and routinely use a pick-up bag. The gallbladder specimens were collected from the gallbladder specimens, and the scope of surgical resection was guided according to the results of intraoperative frozen pathological examination (recommended intensity: strong; consistency strength: strong; α score: 85.0%).

(5) Lymph node dissection

1. Scope of lymph node dissection: When the preoperative imaging examination is highly suspicious of positive lymph nodes in group 16, PET-CT examination or laparoscopic exploration can be performed, and lymph node biopsy in group 16 (group 16a or 16b1), positive lymph nodes in group 16 means that there is distant metastasis, radical resection should be abandoned, and re-evaluation should be performed after conversion therapy. At present, there is a great deal of controversy about expanded lymph node dissection, and the existing literature shows that extended lymph node dissection cannot bring survival benefits to patients, and should be carefully selected or explored. Lymph node metastasis is an important prognostic factor for gallbladder cancer, and regional lymph node dissection is essential. The scope of lymph node dissection for gallbladder cancer is still controversial, and most scholars believe that for patients with gallbladder cancer with stage T1b and above, regional lymph node dissection is recommended: in addition to hepatoduodenal ligament lymph nodes, lymph nodes should be dissected next to the common hepatic artery and posterior superior to the pancreatic head, and the number of lymph nodes dissected should be ≥ 6 [16,21, 22, 23, 24].

Recommendation 7: When preoperative imaging examination suspects that there is lymph node metastasis in group 16, PET-CT examination or laparoscopic exploratory biopsy is recommended, and radical surgery should be abandoned if the lymph node in group 16 is found to be positive (recommended intensity: moderate; consistency strength: conditional; α score: 80.0%).

2. Lymph node dissection process and precautions: The lymph node dissection sequence can be selected according to the operator's habits: when the right approach is dissected, after opening the Kocher incision, the lymph nodes in the 13a group and the 12p group behind the portal vein are first dissected, and the lymphatic fat and fibrous connective tissue behind the bile duct and around the right hepatic artery are standardized, and if necessary, the right hepatic artery is swept upwards to the right hepatic artery, as well as around the right anterior and right posterior branches of the portal vein, so as to avoid the tumor remaining around the right liver pedicle. When dissecting the left side of the bile duct, attention should be paid to fully dissecting the common hepatic artery, the hepatic propria artery, the left hepatic artery, the middle hepatic artery and the lymphatic fat and fibrous connective tissue around the bile duct, and pay attention to the dissection of the gastroduodenal artery and portal vein. Lymphadipose tissue between the pancreatic heads, to avoid residue, and to protect the gastroduodenal artery to avoid pseudoaneurysm formation of the gastroduodenal artery due to thermal injury or excessive traction of ultrasound, and to avoid damage to the bile duct wall and the artery at 3 o'clock and 9 o'clock during bile duct dissection to avoid postoperative bile duct ischemia necrosis and biliary fistula caused by peribile duct dissection [25].

In the left approach, the perihepatic lymph nodes are dissected first, followed by the ossification of the hepatoduodenal ligament, and then the group 13a lymph nodes. During the operation, the principle of "taking into account both left and right, from caudal to cephalad" can also be adopted, and the whole piece can be removed as much as possible. In view of the spread of gallbladder cancer along the nerve and vascular sheath, opening the vascular sheath to achieve intrathecal dissection and ossification can be considered. If the lymph nodes are swollen and fused into clumps during the operation, and it is difficult to complete the dissection of the whole block, it is recommended to switch to open surgery.

Recommendation 8: For patients with T1b stage and above gallbladder cancer, lymph node dissection is recommended, and the scope of dissection is based on the recommendations in the Guidelines for the Diagnosis and Treatment of Gallbladder Cancer (2019 Edition), and it is recommended that the dissection is carried out to the second station, and the anatomical criteria for open surgical lymph node dissection must be met (recommended intensity: strong; consistency strength: strong; α score: 87.5%).

(6) Treatment of liver resection and liver section in LRRGC

For patients with gallbladder cancer at different stages, the scope of liver resection is still controversial. The scope and principle of hepatic resection in LRRGC are consistent with open surgery, as recommended in the Guidelines for the Diagnosis and Treatment of Gallbladder Cancer (2019 Edition) [16]. According to the operator's habits, laparoscopic vascular occlusion forceps or occlusion bands are used to block hepatic hilar blood flow.

Liver resection for gallbladder cancer above T2b strives to achieve anatomical resection. In the case of standard liver 4b+5 segment resection, the Glisson sheath of the 4b segment of the liver was first dissected on the right side of the round ligament of the liver, the hepatic ischemia line of the 4b segment of the liver was confirmed after dissection, the liver parenchyma was dissected from left to right along the upper edge of the hepatic door plate, the Glisson sheath of the right anterior lobe was exposed, and the Glisson sheath of the 5th segment of the liver was exposed upward, and the anatomical liver 4b+5 segment resection was completed along the ischemic area of the liver surface of the 5th segment after pre-blockade.

When the right hemihepatic resection is expanded, the right liver needs to be fully released to the right wall or anterior wall of the inferior vena cava, and Glisson intrathecal dissection, separation, and ligation of the right hepatic artery and the right portal vein branch to reduce intraoperative bleeding and mark the broken liver line. After resection of the branch of the middle hepatic vein segment 4b, the main trunk of the middle hepatic vein was searched upwards, and the right hepatic resection was performed along the main trunk of the middle hepatic vein. Hepatic hemorrhage can be treated with hemostatic systems such as 100-gram forceps and radiofrequency ablation, and sutures to stop bleeding if necessary. Specific recommendations for liver parenchymal dissection and wound hemostasis can be found in the Chinese Expert Consensus on Laparoscopically Assisted Liver Resection in the Treatment of Hepatocellular Carcinoma (2020 Edition) and the Chinese Expert Consensus on Hemostasis in Liver Surgery (2023 Edition) [3,26].

Recommendation 9: For the extent of liver resection in LRRGC, please refer to the Guidelines for the Diagnosis and Treatment of Gallbladder Cancer (2019 Edition), and laparoscopic vascular occlusion forceps or occlusion bands are selected for hilar blood flow blockade according to the operator's habits. For specific operational recommendations on liver parenchymal dissection and wound hemostasis, please refer to the Chinese Expert Consensus on Laparoscopically Assisted Liver Resection in the Treatment of Hepatocellular Carcinoma (2020 Edition) and the Chinese Expert Consensus on Hemostasis in Liver Surgery (2023 Edition) (recommended strength: strong; consistency strength: strong; α score: 87.5%).

(7) Treatment of extrahepatic bile ducts and biliary-intestinal anastomosis

Intraoperative cystic duct stump requires routine cryopathological examination, and extrahepatic cholangioresection and biliary-intestinal anastomosis are indicated if the results suggest a positive cystic duct stump, cystic duct cancer, or lymph node invasion of the bile duct [27]. Before dissecting the extrahepatic bile duct, it is recommended to clamp the proximal bile duct with blocking forceps or synthetic clips to avoid bile leakage and tumor dissemination. When LRRGC with extrahepatic cholangioresection is required, it should be carefully selected according to the tumor invasion and metastasis, combined with the laparoscopic operation experience of each center, and if laparoscopic-assisted surgery is difficult to evaluate during surgery or cannot meet the anatomical criteria of open surgery, it should be switched to open surgery to ensure the long-term efficacy of patients.

According to the recommendations in the "Chinese Expert Consensus on Suture Techniques and Suture Materials Selection for Laparoscopic Hepatobiliary Surgery (2021 Edition)", according to the diameter and texture of the bile duct, the biliary-intestinal anastomosis can be completed with intermittent or continuous sutures with appropriate sutures. The biliary support tube should be placed according to the diameter, texture, and blood supply of the bile duct during surgery to prevent anastomotic stenosis, and if the laparoscopic anastomosis is difficult or unsatisfactory, the biliary-intestinal anastomosis can be completed with a median abdominal incision [28].

Recommendation 10: Prophylactic cholangiectomy is not recommended. Extrahepatic bile duct resection is recommended for patients with positive cystic duct stumps, cystic duct cancer, or lymph node invasion of the bile ducts, and the upper and lower bile duct margins should be sent for intraoperative frozen pathology to ensure that negative margins are obtained. If laparoscopic-assisted surgery fails to meet the criteria for open surgery in intraoperative evaluation, it should be converted to open surgery (recommended intensity: strong; consistency intensity: conditional; α score: 80.0%).

Recommendation 11: The biliary-intestinal anastomosis method and suture selection refer to the recommendations in the "Chinese Expert Consensus on Suture Techniques and Suture Material Selection for Laparoscopic Hepatobiliary Surgery (2021 Edition)". When laparoscopic anastomosis is difficult, the biliary-intestinal anastomosis can be completed with a median abdominal incision to ensure the quality of the anastomosis (recommended strength: strong; consistency strength: strong; α score: 82.5%).

(8) Indications for open surgery

If there is uncontrollable bleeding during the operation, the patient is difficult to tolerate pneumoperitoneum, it is difficult to expose, the lymph nodes are fused into clumps, the intraoperative separation is difficult, the tumor involves the blood vessels and requires revascularization and reconstruction, the combined multi-organ resection is required, the anatomical standard of open resection is difficult to be reached under laparoscopy, and the laparoscopic assisted surgery is too long, it is recommended to transfer to open surgery in time to ensure the safety and quality of radical surgery.

Recommendation 12: If there is uncontrollable bleeding during the operation, the anatomical criteria for open surgical resection cannot be met under laparoscopy, and the tumor invades the organs and blood vessels, it is difficult to ensure R0 resection, etc., the patient should be transferred to open surgery in time (recommended strength: strong; consistency strength: strong; α score: 97.5%).

3. Principles of surgical management of delayed diagnosis of gallbladder cancer with reradical resection

(1) Indications and principles for re-radical resection of gallbladder cancer with delayed diagnosis

Delayed diagnosis of gallbladder cancer has a certain residual tumor rate (27 percent for the liver, 9 percent for the cystic duct, and 24 percent for the lymph nodes), which is an independent prognostic factor, and repeated radical resection can help prolong survival [28]. As for the timing of reoperation, there are no major case reports to clarify this. Previous studies have shown that reoperation is appropriate at 4~8 weeks postoperatively [27], and recent literature recommends reoperation within 4 weeks or even 2 weeks after surgery [29, 30]. It is recommended that the patient should be individualized according to the patient's condition, and if the patient's condition allows, early reradical resection can be considered, and if the tumor has progressed significantly before reradical resection, neoadjuvant therapy can be considered before reoperation, and then reoperation can be evaluated. The surgical aspect of primary cholecystectomy is less invasive, and early reoperation may help reduce lymph node metastases, abdominal metastases, and invasion of surrounding organs from residual tumors while waiting. In addition, the early adhesions are mainly inflammatory adhesions, which are easier to separate, while the later adhesions are mainly fibrous connective tissue adhesions, which are often denser and difficult to separate, and are easy to damage the bile ducts, gastrointestinal tract and other surrounding organs. Resection of the puncture foramen sinus tract at the time of reoperation does not improve patient outcomes and is therefore not recommended for routine resection [23, 24,31]. Procedures such as lymph node dissection and hepatic resection for reoperation are described in radical cholecystectomy for primary surgery [16].

Due to the complexity of reradical resection, open radical resection remains the preferred procedure. With the accumulation of laparoscopic reoperation experience, laparoscopic-assisted reradical resection to delay the diagnosis of gallbladder cancer may also be safe and feasible. In previous multicenter retrospective studies (n = 255), laparoscopic-assisted reradical resection of gallbladder cancer was similar in terms of the number of intraoperative lymph node dissections, surgical margins, postoperative complications, and long-term survival [32]. For strictly selected delayed diagnosis of gallbladder cancer (stage T1b, T2, without obvious hepatoduodenal lymph node metastasis), laparoscopic-assisted reradical resection can be carried out on a trial basis in a center with rich experience in laparoscopic-assisted surgery to accumulate multi-center clinical experience.

Recommendation 13: Open radical resection remains the preferred surgical modality for delaying the diagnosis of gallbladder cancer. For those with strictly selected delayed diagnosis of gallbladder cancer (T1b, T2 stage, no obvious hepatoduodenal lymph node metastasis), LRRGC can be tried in centers with experience in laparoscopic assisted surgery, and if necessary, it can be transferred to open surgery (recommended intensity: moderate; consistency strength: conditional; α score: 70.0%).

(2) Preoperative evaluation and precautions for re-radical resection of gallbladder cancer with delayed diagnosis

Before surgery, it is important to collect complete data from the previous surgery to determine the surgical method at the time of the initial operation, whether the gallbladder has been ruptured, whether a retrieval bag is used, whether biliary exploration is performed, and whether there are liver, lymph nodes, and peritoneal metastases [33]. The pathological examination results of the initial surgery were analyzed in detail, the tumor location, the depth of invasion of the gallbladder wall, and the cuffed end of the cystic duct were clarified, and if necessary, the pathology department was consulted again, and the TNM was restaged in combination with the preoperative examination, and the surgical plan was formulated in coordination.

Recommendation 14: Before reoperation for delayed diagnosis of gallbladder cancer, the intraoperative situation and pathological examination results of the initial operation should be comprehensively analyzed, and if necessary, pathology consultation should be performed for re-staging, combined with preoperative examination, and the surgical plan should be formulated in coordination (recommended strength: strong; consistency strength: strong; α score: 82.5%).

(3) Delayed diagnosis of gallbladder cancer intraoperative suspicious tissue for examination

In order to avoid residual tumor due to deviation of the initial sample or tumor progression during the waiting period, it is recommended to perform a cryopathological examination of the suspected gallbladder-neck canal at the time of reoperation. The incision margin of the gallbladder neck duct should be as close to the bile duct as possible. During the reoperation, the gallbladder-neck canal is often tightly adhered to the surrounding bile duct, right hepatic pedicle, gastric antrum or duodenum, and care should be taken to avoid collateral injury to the surrounding organs during the separation process. It is recommended to perform intraoperative multi-point frozen pathological examination for all suspicious adhesion tissues, including adherent omentum, peribile duct adhesion tissue, T-duct sinus tract, gastric antrum, adhesion between duodenum and gallbladder bed, right liver pedicle surrounding tissue, residual gallbladder bed and other areas, and determine the scope of resection according to the results of rapid pathological examination: if the biopsy of gastric antrum and periduodenal adhesion tissue is positive, it is recommended to perform gastric antrum, Local duodenal resection; if bile duct adhesion tissue is positive, additional hepatic cholangioectomy is recommended; if biopsy of the surrounding tissue of the right liver pedicle is positive, an expanded right hemihepatectomy may be considered if the remaining liver volume is sufficient; if necessary, the affected organs and adhesions should be removed and dissected entirely.

Recommendation 15: In the case of reoperation, it is recommended that the suspicious gallbladder-cervical canal be sent for pathological examination during the operation, and the perigallbladder-cervical adhesions should be carefully separated during the reoperation to avoid collateral damage to the surrounding organs. It is recommended to perform intraoperative multi-point frozen pathological examination of suspicious adhesion tissues, and select the surgical method based on comprehensive evaluation of preoperative planning (recommended strength: strong; consistency strength: strong; α score: 85.0%).

4. Specimen submission and postoperative follow-up

During the operation, a pick-up bag is routinely used to avoid peritoneal spread and puncture hole metastasis. In cases with the potential for peritoneal disseminated metastasis, intraperitoneal irrigation with chemotherapy agents such as hypotonic normal saline and mitomycin or intraperitoneal thermal perfusion may be considered to reduce the incidence of postoperative abdominal metastasis [34, 35, 36, 37]. Postoperatively, each resection margin of the specimen should be labeled, and the lymph nodes dissected should be accurately labeled and grouped to facilitate postoperative pathological staging. For the prevention and treatment of postoperative complications, please refer to the recommendations in the Chinese Clinical Practice Guidelines for Enhanced Recovery Surgery (2021 Edition) and the Chinese Expert Consensus on the Perioperative Management of Hepatic Resection for Liver Cancer (2021 Edition) [38, 39]. It is recommended to have a follow-up examination every 3~6 months after surgery, including tumor marker testing, liver function tests, CT or MRCP examinations, etc. It is recommended to establish a standardized database, follow up and update it regularly, and conduct a multicenter clinical study.

Recommendation 16: Establish a standardized database, regularly follow up and update patients, and ensure the quality of data is an important factor in determining the long-term efficacy of LRRGC (recommendation strength: strong; consistency strength: strong; α score: 97.5%).

The operation of LRRGC is complex, and the fundamental principle and purpose of LRRGC should be carried out according to the experience of each center, and the surgical operation process should be gradually standardized and optimized, so as to ensure the safety of patients and long-term efficacy. At the same time, it is necessary to carry out a large-scale case-control study of LRRGC and traditional open surgery in conjunction with multiple centers to further explore the indications, contraindications, precautions, diagnosis and treatment standards, quality control and long-term efficacy of LRRGC, and jointly promote the standardization and improvement of laparoscopic-assisted radical cholecystectomy.

Experts who participated in the discussion and writing of this expert consensus

Team Leader: Zhiwei Quan (Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Cheng Nansheng (West China Hospital, Sichuan University), Qingguang Liu (The First Affiliated Hospital of Xi'an Jiaotong University)

Members of the writing team (in alphabetical order of surname):

Yajin Chen (Sun Yat-sen Memorial Hospital, Sun Yat-sen University), Shi Cheng (Beijing Tiantan Hospital, Capital Medical University), Zhangjun Cheng (Zhongda Hospital, Southeast University), Xiaxing Deng (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine), Xiaohui Duan (Hunan Provincial People's Hospital), Geng Zhimin (The First Affiliated Hospital of Xi'an Jiaotong University), Wei Guo (Beijing Friendship Hospital, Capital Medical University), Yu He (The First Affiliated Hospital of Army Medical University), Hong Defei (Sir Run Run Shaw Hospital, Zhejiang University School of Medicine), Binglu Li (Peking Union Medical College Hospital), Bo Li (Affiliated Hospital of Southwest Medical University), Jiangtao Li (The Second Affiliated Hospital of Zhejiang University School of Medicine), Jingdong Li (Affiliated Hospital of North Sichuan Medical College), Jing Li (Editorial Department of Chinese Journal of Surgery), Xiangcheng Li (The First Affiliated Hospital of Nanjing Medical University), Chao Liu (Sun Yat-sen Memorial Hospital, Sun Yat-sen University), Houbao Liu (Zhongshan Hospital Affiliated to Fudan University), Rong Liu (The First Medical Center of PLA General Hospital), Yingbin Liu (Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Lou Jianying (The Second Affiliated Hospital of Zhejiang University School of Medicine), Lu Qiping (PLA Central Theater General Hospital), Mao Xianhai (Hunan Provincial People's Hospital), Qiu Yudong (Drum Tower Hospital Affiliated to Nanjing University School of Medicine), Shao Chenghao (Second Affiliated Hospital of Naval Medical University), Tang Zhaohui (Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Wang Guangyi (The First Hospital of Jilin University), Wang Jian (The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Wang Jianming (Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology), Qiusheng Wang (Peking University People's Hospital), Wang Wei (East China Hospital Affiliated to Fudan University), Yan Qiang (Huzhou Central Hospital), Yin Baobing (Huashan Hospital Affiliated to Fudan University), Yin Xinmin (Hunan Provincial People's Hospital), Yu Decai (Drum Tower Hospital Affiliated to Nanjing University School of Medicine), Zhang Chengwu (Zhejiang Provincial People's Hospital), Zhang Kai (Yixing Hospital Affiliated to Jiangsu University), Zhang Yongjie (The Third Affiliated Hospital of Naval Medical University), Zhao Guodong (First Medical Center of PLA General Hospital), Yongyi Zeng (Mengchao Hepatobiliary Hospital, Fujian Medical University), Yamin Zheng (Xuanwu Hospital, Capital Medical University), Di Zhou (Xinhua Hospital, Shanghai Jiao Tong University School of Medicine)

Authors: Li Fuyu (West China Hospital, Sichuan University), Hu Haijie (West China Hospital, Sichuan University), Jin Yanwen (West China Hospital, Sichuan University), Gong Wei (Xinhua Hospital, Shanghai Jiao Tong University School of Medicine)

bibliography

[1]

RoaJC,GarcíaP,KapoorVK,et al. Gallbladder cancer[J]. Nat Rev Dis Primers,2022,8(1):69. DOI: 10.1038/s41572-022-00398-y.

[2]

Pancreatic Surgery Group of Chinese Society of Surgery, Pancreatic Minimally Invasive Therapy Group of Pancreatic Disease Branch of China Association for the Promotion of International Exchange in Health Care, Pancreatic Minimally Invasive Group of Pancreatic Disease Professional Committee of Chinese Research Hospital Association, et al. Expert consensus on laparoscopic pancreaticoduodenectomy (Attached: surgical process and main steps)[J].Chinese Journal of Surgery, 2017, 55(5): 335-339. DOI: 10.3760/cma.j.issn.0529-5815.2017.05.004.

[3]

Hepatobiliary and Pancreatic Surgery Committee of Chinese Association of Research Hospitals. Chinese expert consensus on laparoscopic-assisted hepatectomy in the treatment of hepatocellular carcinoma (2020 edition)[J]. Chinese Journal of Digestive Surgery, 2020, 19(11): 1119-1134. DOI: 10.3760/cma.j.cn115610-20201029-00682.

[4]

ZHANG Lei, CHEN Yajin. Chinese Journal of Digestive Surgery, 2020, 19(1):46-49. DOI: 10.3760/cma.j.issn.1673-9752.2020.01.007.

[5]

HanHS, YoonYS, AgarwalAK, et al. Laparoscopic surgery for gallbladder cancer: an expert consensus statement[J]. Dig Surg, 2019, 36(1): 1-6. DOI: 10.1159/000486207.

[6]

ReberPU,BaerHU,PatelAG,et al. Port site metastases following laparoscopic cholecystectomy for unsuspected carcinoma of the gallbladder[J]. Z Gastroenterol,1998,36(10):901-907.

[7]

OuchiK,MikuniJ,KakugawaY. Laparoscopic cholecystectomy for gallbladder carcinoma: results of a Japanese survey of 498 patients[J]. J Hepatobiliary Pancreat Surg,2002,9(2):256-260. DOI: 10.1007/s005340200028.

[8]

WakaiT,ShiraiY,YokoyamaN,et al. Early gallbladder carcinoma does not warrant radical resection[J]. Br J Surg,2001,88(5): 675-678. DOI: 10.1046/j.1365-2168.2001.01749.x.

[9]

AbramsonMA,PandharipandeP,RuanD,et al. Radical resection for T1b gallbladder cancer: a decision analysis[J]. HPB (Oxford),2009,11(8):656-663. DOI: 10.1111/j.1477-2574.2009.00108.x.

[10]

ShindohJ, de AretxabalaX, AloiaTA, et al. Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study[J]. Ann Surg,2015,261(4):733-739. DOI: 10.1097/SLA.0000000000000728.

[11]

LeeH,ChoiDW,ParkJY,et al. Surgical Strategy for T2 Gallbladder Cancer According to Tumor Location[J]. Ann Surg Oncol,2015,22(8):2779-2786. DOI: 10.1245/s10434-014-4300-7.

[12]

AlMasriS,NassourI,TohmeS,et al. Long-term survival following minimally invasive extended cholecystectomy for gallbladder cancer: a 7-year experience from the National Cancer Database[J]. J Surg Oncol,2020,122(4):707-715. DOI: 10.1002/jso.26062.

[13]

ZhaoX, LiXY, JiW. Laparoscopic versus open treatment of gallbladder cancer: a systematic review and Meta-analysis[J]. J Minim Access Surg,2018,14(3):185-191. DOI: 10.4103/jmas. JMAS_223_16.

[14]

NakanishiH, MiangulS, OluwaremiTT, et al. Open versus laparoscopic surgery in the management of patients with gallbladder cancer: a systematic review and Meta-analysis[J]. Am J Surg,2022,224(1Pt B):348-357. DOI: 10.1016/j.amjsurg.2022.03.002.

[15]

AhmedSH, UsmaniS, MushtaqR,et al. Role of laparoscopic surgery in the management of gallbladder cancer: Systematic review & Meta-analysis[J]. Am J Surg,2023,225(6):975-987. DOI: 10.1016/j.amjsurg.2023.01.008.

[16]

Biliary Surgery Group of the Chinese Society of Surgery, Biliary Surgery Committee of the Surgeon Branch of the Chinese Medical Doctor Association. Guidelines for the diagnosis and treatment of gallbladder cancer (2019 edition)[J].Chinese Journal of Surgery,2020, 58(4): 243-251. DOI: 10.3760/cma.j.cn112139-20200106-00014.

[17]

de Savornin LohmanE,de BitterT, van LaarhovenC, et al. The diagnostic accuracy of CT and MRI for the detection of lymph node metastases in gallbladder cancer: a systematic review and Meta-analysis[J]. Eur J Radiol,2019, 110: 156-162. DOI: 10.1016/j.ejrad.2018.11.034.

[18]

KumaranV,GulatiS,PaulB, et al. The role of dual-phase helical CT in assessing resectability of carcinoma of the gallbladder[J]. Eur Radiol,2002,12(8):1993-1999. DOI: 10.1007/s00330-002-1440-0.

[19]

Guidelines Working Committee of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of biliary tract malignancies, 2023 [M]. Beijing: People's Medical Publishing House, 2023.

[20]

The significance of a multidisciplinary team to standardize the collection and reporting of biliary tract tumor pathology[J].Chinese Journal of Digestive Surgery,2017,16(1):47-52.DOI: 10.3760/cma.j.issn.1673-9752.2017.01.010.

[21]

NagakuraS, ShiraiY,YokoyamaN,et al. Clinical significance of lymph node micrometastasis in gallbladder carcinoma[J]. Surgery,2001,129(6):704-713. DOI: 10.1067/msy.2001.114764.

[22]

ShiraiY,WakaiT,HatakeyamaK. Radical lymph node dissection for gallbladder cancer: indications and limitations[J]. Surg Oncol Clin N Am, 2007, 16(1):221-232. DOI: 10.1016/j.soc.2006.10.011.

[23]

OkumuraK,GognaS,GachabayovM,et al. Gallbladder cancer: Historical treatment and new management options[J]. World J Gastrointest Oncol,2021,13(10):1317-1335. DOI: 10.4251/wjgo.v13.i10.1317.

[24]

AloiaTA, JárufeN, JavleM, et al. Gallbladder cancer: expert consensus statement[J]. HPB (Oxford),2015,17(8):681-690. DOI: 10.1111/hpb.12444.

[25]

Hepatobiliary and Pancreatic Surgery Committee of Chinese Research Hospital Association, National Health Commission Public Welfare Industry Scientific Research Expert Committee. Expert consensus on the application of biliary anastomosis for hepatobiliary stone disease (2019 edition)[J].Chinese Journal of Digestive Surgery,2019,18(5):414-418.) DOI: 10.3760/cma.j.issn.1673-9752.2019.05.002.

[26]

Committee of Liver Surgeons, Surgeon Branch of Chinese Medical Doctor Association. Chinese Expert Consensus on Hemostasis in Liver Surgery (2023 Edition)[J/CD].Chinese Literature on General Surgery(Electronic Edition),2023,17(2):81-92.) DOI: 10.3877/cma.j.issn.1674-0793.2023.02.001.

[27]

GaniF, BuettnerS, MargonisGA,et al. Assessing the impact of common bile duct resection in the surgical management of gallbladder cancer[J]. J Surg Oncol, 2016,114(2): 176-180. DOI: 10.1002/jso.24283.

[28]

Chinese Society of Surgery. Chinese expert consensus on suture technology and suture material selection for biliary tract surgery (2018 edition)[J].Chinese Journal of Practical Surgery,2019,39(1):15-20.) DOI: 10.19538/j.cjps.issn1005-2208.2019.01.05.

[29]

IsambertM,LeuxC,MétairieS,et al. Incidentally- discovered gallbladder cancer: when,why and which reoperation? [J]. J Visc Surg,2011,148(2):e77-e84. DOI: 10.1016/j.jviscsurg.2011.02.005.

[30]

DuJ,YangXW,WenZJ,et al. Relationship between Prognosis and Time Interval from Cholecystectomy to Reoperation in Postoperative Incidental Gallbladder Carcinoma[J]. Chin Med J (Engl), 2018,131(20):2503-2505. DOI: 10.4103/0366-6999.243565.

[31]

Berger-RichardsonD,ChesneyTR,EnglesakisM,et al. Trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer: a systematic review[J]. Surgery,2017,161(3):618-627. DOI: 10.1016/j.surg.2016.08.007.

[32]

VegaEA,De AretxabalaX,QiaoW,et al. Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer[J]. Br J Surg,2020, 107(3): 289-300. DOI: 10.1002/bjs.11379.

[33]

SøreideK, GuestRV, HarrisonEM, et al. Systematic review of management of incidental gallbladder cancer after cholecystectomy[J]. Br J Surg,2019,106(1):32-45. DOI: 10.1002/bjs.11035.

[34]

GlehenO,KwiatkowskiF,SugarbakerPH,et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study[J]. J Clin Oncol,2004,22(16):3284-3292. DOI: 10.1200/JCO.2004.10.012.

[35]

GuoJ, XuA, SunX, et al. Combined Surgery and Extensive Intraoperative Peritoneal Lavage vs Surgery Alone for Treatment of Locally Advanced Gastric Cancer: The SEIPLUS Randomized Clinical Trial[J]. JAMA Surg,2019,154(7):610-616. DOI: 10.1001/jamasurg.2019.0153.

[36]

KuramotoM,ShimadaS,IkeshimaS,et al. Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma[J]. Ann Surg,2009,250(2):242-246. DOI: 10.1097/SLA.0b013e3181b0c80e.

[37]

DesiderioJ,ChaoJ,MelstromL,et al. The 30-year experience-A meta-analysis of randomised and high-quality non-randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer[J]. Eur J Cancer,2017, 79:1-14. DOI: 10.1016/j.ejca.2017.03.030.

[38]

Chinese Society of Surgery, Chinese Society of Anesthesiology. Chinese Journal of Practical Surgery,2021, 41(9):961-992. DOI: 10.19538/j.cjps.issn1005-2208.2021.09.01.

[39]

Cross-Strait Medical and Health Exchange Association Cancer Prevention and Treatment Expert Committee. Chinese expert consensus on perioperative management of hepatectomy for liver cancer (2021 edition)[J].Chinese Journal of Oncology,2021,43(4):414-430.) DOI: 10.3760/cma.j.cn112152-20210314-00228.

Expert Consensus on Laparoscopic Radical Resection of Gallbladder Cancer (2023)

Read on