- Email: [email protected]
RETRACTED: Laparoscopic cholecystectomy and unsuspected gallbladder cancer
EJSO 2001; 27: 225–228 doi:10.1053/ejso.2000.1036, available online at http://www.idealibrary.com on
REVIEWS
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Laparoscopic cholecystectomy and unsuspected gallbladder cancer
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F. Romano, C. Franciosi, R. Caprotti, S. De Fina, G. Porta, G. Visintini and F. Uggeri Department of General Surgery, San Gerardo Hospital, II University of Milan – Bicocca
AC
Gallbladder cancer is a relatively uncommon malignancy. Its presentation is similar to that of gallstone disease and sometimes with non-specific symptoms. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall gallbladder cancers have a poor prognosis, despite surgery or adjuvant therapies. However, in selected cases, a favourable outcome can be expected and the less favourable predicted outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted post-operatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope. 2001 Harcourt Publishers Ltd
R
Key words: gallbladder neoplasms; laparoscopic cholecystectomy; neoplasm seeding; reoperation; unsuspected carcinoma.
ET
INTRODUCTION
R
Gallbladder cancer (GBC) is the fifth most common neoplasm of the digestive tract, and is found in approximately 1.5–3% of cholecystectomy specimens.1–2 In about only 10–20% of patients is GBC suspected pre-operatively;3–6 in the rest diagnosis is made at the time of surgery or post-operatively by the pathologist. In such cases the surgeon is left with the decision of how to proceed with management of the patient. Usually the management is based on TNM stage of the gallbladder cancer (Table 1),7,8 though factors such as grade and histological morphology could have prognostic relevance. Pre-operative diagnosis of GBC depends on clinical suspicion and careful review of radiological work-up.
Correspondence to: Fabrizio Romano, Department of General Surgery, San Gerardo Hospital, II University of Milan – Bicocca, Via Donizetti 106, 20052 Monza, Italy. 0748–7983/01/030225+04 $35.00/0
Symptoms noted in 50–60% of cases are right upper quadrant pain, nausea, vomiting and anorexia, while weight loss and fatigue are less common.9 Often GBC is associated with a change in previously stable lithic symptomatology10 and in 25% there is a presence of an abdominal mass.11 Signs of suspicion at US or CT scan are a mass filling or replacing the gallbladder, thickening of the wall, infiltration of the liver bed and polypoid lesions larger than 10 mm.12–14 If GBC is suspected pre-operatively, open cholecystectomy must be performed to allow complete evaluation of the extension of disease and wide resection if necessary. Initial laparoscopic exploration may be used to evaluate the extent of disease. Because there is not a proven effective adjuvant therapy available for GBC,15,16 the best treatment is complete surgical extirpation of the cancer. The optimal operation is one in which the gallbladder is not disrupted, negative margins are achieved and involved lymphatics are removed.17,18 Since even carcinoma in situ is demonstrated to seed the peritoneal cavity with consequent carcinomatosis if 2001 Harcourt Publishers Ltd
226
REVIEWS
Regional lymph nodes N1 Tumour in cystic, pericoledochal or hilar lymph nodes N2 Tumour in peripancreatic, periduodenal, coeliac or superior mesenteric lymph nodes
T1, T2, T1, T4,
N0, M0 N0, M0 T2 or T3, N1, M0 N2 or M1
R
Stage 1 2 3 4
AC
Distant metastases M1 Distant metastases
ET
gallbladder is violated,19 meticulous detail in dissection must be carried out to avoid disruption of the gallbladder. Even if usually GBC is associated with a limited lymph-node involvement in the area of cystic duct, choledochus, or portahepatis, the surgical dissection involves en bloc removal of the lymph nodes of the coeliac axis, portahepatis, hepatoduodenum ligament, hepatic artery and peripancreatic area. The extent of hepatic resection advocated for a radical surgery varies from resection of the gallbladder bed with 2 cm of hepatic parenchyma (extended cholecystectomy) to anatomic resection with removal of segments IV and V.20–22 Furthermore, because of the tendency for GBC to recur at laparoscopic port sites, excision of the port sites is advocated due to multiple case reports of implantation after LC.23–26 This extended surgery may be performed with expected mortality and morbidity of 0 to 8.5% and 5% to 11% respectively.27,28 In case of gallbladder cancer diagnosed in association with LC four scenarios will be discussed: (1) GBC noted on final pathology after LC; (2) GBC noted after removal of the specimen and opening of the gallbladder at time of surgery; (3) GBC suspected during LC due to difficult dissection; and (4) extensive disease noted on placement of the laparoscope.
R
After completion of an open or laparoscopic cholecystectomy, the specimen should be opened and inspected for mucosal abnormalities. If the gallbladder is not inspected or a pathological process is not identified, GBC may not be diagnosed until after surgery. In this case, the pathological tumour stage (Tx) may be the only information available to guide therapy. If the pathologist analysis reveals a Tis or T1 stage, the prognosis is favourable. If there has been no gallbladder violation, the margins are negative and no signs of intraperitoneal spread are noted, a 5 year survival of 80% to 100% is reported after cholecystectomy alone.29–31 No improvement is noted with a reoperation in this group, so cholecystectomy can be considered curative. If the margins are positive at cystic stump, reoperation and biliary resection is necessary to avoid early recurrence.32 In case of gallbladder perforation (reported in 26–33% of LC),33,34 the problem is one of peritoneal seeding and not local control of the disease. In this case local resection for peritoneal spillage or gallbladder contents, even if advocated by some, is probably not warranted.35 For patients with stage T2, T3 or T4 prognosis is not so good. Recent reports show that 5 year survival for patients with T2 GBC can be improved with extended cholecystectomy from 40% to 90%.36 The survival benefit may be compromised if disruption of gallbladder with tumour spillage occurs at the time of LC. Occasionally long-term survival is noted in patients with T3 or T4 stage, however there is a high likelihood of tumour spillage and subsequent peritoneal carcinomatosis in patients treated with simple cholecystectomy. Over 50% of patients who are candidates for re-exploration with curative intent will have disease precluding R0 resection found at operation.37 Moreover, reoperation and resection for T3 and T4 GBC results in early recurrence with poor 5 year survival.38 However re-exploration may be considered in patients with T3 or T4 disease, because surgical resection offers the only chance for cure. If this is the case, preoperative evaluation of the local extent of tumour, of possible presence of metastatic disease and of the patient’s ability to withstand a major operation must be analysed. To obtain a R0 resection, extended cholecystectomy should suffice in T2 stage, but hepatic resection would be necessary in T3 and T4 patients.
D
Primary tumour Tis Carcinoma in situ T1 Tumour invading mucosa (pT1a) Tumour invading muscle layer (pT1b) T2 Tumour invading the perimuscular connective tissue with no extension beyond the serosa or into the liver T3 Tumour invading beyond the serosa or into adjacent organs (extending 2 cm or less into the liver) T4 Tumour extending more than 2 cm into the liver or two or more adjacent organs
GBC noted on final pathology after laparoscopic cholecystectomy
TE
Table 1 TNM staging system for gallbladder carcinoma
GBC noted at extraction of the specimen during laparoscopic cholecystectomy The gallbladder should be inspected after removal of the specimen at the time of surgery. If a GBC is suspected, a frozen section should be performed. When a GBC is discovered at this time many of the principles previously stated have to be applied. In case of Tis or T1 stage,
REVIEWS
227
REFERENCES
1. Yamaguchi K, Chijiiwa K, Ichimiya H, et al. Gallbladder carcinoma in the era of laparoscopic cholecystectomy. Arch Surg 1996; 131: 981–5. 2. Wibbenmayer LA, Wade TP, Chen RC, et al. Laparoscopic cholecystectomy can disseminate in situ carcinoma of the gallbladder. J Am Coll Surg 1995; 181: 504–10. 3. Donohue JH, Nagorney DH, Grant CS, et al. Carcinoma of the gallbladder. Does radical resection improve outcome? Arch Surg 1990; 125: 237–41. 4. Shirai Y, Yoshida K, Tsukada K, Muto T. Inapparent carcinoma of the gallbladder. An appraisal of a radical second operation after simple cholecystectomy. Ann Surg 1992; 215: 326–31. 5. Yamaguchi K, Tsuneyoshi M. Subclinical gallbladder carcinoma. Am J Surg 1992; 163: 382–6. 6. Wanebo HJ, Castle WN, Fechner RE. Is carcinoma of the gallbladder a curable lesion? Ann Surg 1982; 195: 624–31. 7. Sumiyoshi K, Nagai E, Chijiiwa Y, Nakayama F. Pathology of carcinoma of the gallbladder. World J Surg 1991; 15: 315–21. 8. AJCC Cancer Staging Manual. American Joint Committee on Cancer. 5th ed. Philadelphia: Lippincott-Raven, 1997; pp. 103–8. 9. Piehler JM, Crichlow RW. Primary carcinoma of the gallbladder. Surg Gynecol Obstet 1978; 147: 929–42. 10. De Aretxabala XA, Roa IS, Burgos LA. Curative resection in potentially resectable tumors of the gallbladder. Eur J Surg 1997; 163: 419–26. 11. Silk YN, Douglass HO, Nava HR, Driscoll DL, Tartarian G. Carcinoma of the gallbladder. The Roswell Park experience. Ann Surg 1989; 210: 751–5. 12. Wibbenmeyer LA, Sharafuddin MJ, Wolverson MK et al. Sonographic diagnosis of unsuspected gallbladder cancer: imaging findings in comparison with benign gallbladder conditions. AJR 1995; 165: 1169–74. 13. Itai Y, Araki T, Yoshikawa K, et al. Computed tomography of gallbladder cancer. Radiology 1980; 137: 713–8. 14. Fultz PJ, Skucas J, Weiss SL. Comparative imaging of gallbladder cancer. J Clin Gastroenterol 1988; 10: 683–92. 15. Pitt HA, Grochow LB, Abrams RA. Cancer of the biliary tree. In De Vita VT, Hellman S, Rosemberg SA (eds). Cancer: Principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven, 1997, pp. 1114–28. 16. Douglass HO, Kim SY, Meropol NJ. Neoplasms of the gallbladder. In: Holland JF, Frei E (eds). Cancer medicine. 4th ed. Baltimore: Williams & Wilkins, 1997: 1955–65. 17. Shirai Y, Yoshida K, Tsukada K, et al. Radical surgery for gallbladder cancer. Long term results. Ann Surg 1994; 216: 565–8. 18. Chijiiwa K, Tanaka M. Carcinoma of the gallbladder: an appraisal of surgical resection. Surgery 1994; 115: 751–6.
AC
cholecystectomy is sufficient. Because of the very uncommon involvement of lymph node at this stage, lymph-node sampling is not advocated.39 Extended cholecystectomy for T2 GBC would be expected to improve survival. The surgeon should perform liver bed resection, resection of extrahepatic duct to achieve negative margins. Prior to resection careful inspection should be undertaken to identify eventual contraindication to extended surgery (Table 2). In case of T3 or T4 cancer, the lesion has almost certainly been violated. Also at this stage careful exploration should be performed to assure the possibility of R0 resection.
Gallbladder cancer is uncommon; if it is diagnosed or suspected pre-operatively, open exploration is indicated. Sometimes GBC may be encountered during laparoscopic cholecystectomy. Therapy is guided by the extent of disease. Patients with T1 stage benefit from cholecystectomy alone. Most cases of T2 stage benefit from extended resection. Some patients with T3 or T4 GBC benefit if a R0 resection can be achieved. In general, contraindications to extended surgery include main portal vein involvement, N2 disease, peritoneal carcinomatosis, extraperitoneal metastasis, bilateral hepatic metastasis, local extension precluding an R0 resection and poor patient condition. Principles of surgical therapy for GBC include avoiding gallbladder violation, achieving negative margins and minimizing morbidity in patients with unresectable disease.
D
Peritoneal carcinomatosis Extrahepatic haematogeneous metastases Main portal vein involvement N2 nodal involvement Bilateral haematogenous hepatic metastases Local extension precluding R0 resection Patient physiologically unfit to undergo operation
CONCLUSIONS
TE
Table 2 Contraindications to extended resection for gallbladder cancer
GBC suspected during laparoscopic cholecystectomy
R
ET
R
If GBC is suspected during LC, the procedure should be converted to open one, unless there is extensive disease precluding resection. The surgeon should proceed with an extensive exploration of peritoneal surface, N1 and N2 lymph nodes and liver (eventually with intraoperative ultrasound). In case of question about the ability to achieve negative margins or the need for extended hepatic resection or extended liver involvement, the procedure should be terminated. Survival benefit in patients with lymph-node involvement appears limited to those in whom the lymph node of the cystic duct, common bile duct and porta hepatis are involved.40 If N2 disease is identified, early recurrence is expected.41 Peritoneal carcinomatosis portends a poor prognosis with a median survival reported of 1–3 months.42 When identified in patients undergoing reoperation, it usually results in early failure and subsequent death. Extended resection is not indicated.
Extensive GBC precluding resection identified on initial inspection If extensive disease is noted during abdominal exploration the goal is to document the extent of disease, to confirm the diagnosis with tissue biopsy, and to provide palliation with minimal morbidity. Cholecystecomy, if technically favourable conditions are present, may be undertaken to avoid subsequent gallbladder complications.42
228
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31. Pitt HA, Dooley WC, Yeo CJ, Cameron JL. Malignancies of the biliary tree. Curr Prob Surg 1995; 32: 1–90. 32. Matsumoto Y, Fujii H, Aoyama H, Yamamoto M, Sugahara K, Suda K. Surgical treatment of primary carcinoma of the gallbladder based on the histologic analysis of 48 surgical specimens. Am J Surg 1992; 163: 239–45. 33. Jones DB, Dunnegan DL, Soper MJ. The influence of intraoperative gallbladder perforation on long-term outcome after laparoscopic cholecystectomy. Surg Endosc 1995; 9: 977–80. 34. Kimura T, Goto H, Takeuchi Y, et al. Intraabdominal contamination after gallbladder perforation during laparoscopic cholecystectomy and its complications. Surg Endosc 1996; 10: 888–91. 35. Collier NA, Blumgart LH. Tumors of the gallbladder. In: Blumgart LH (ed). Surgery of the liver and biliary tract. 2nd ed. Edinburgh: Churchill Livingstone, 1994, pp. 955–65. 36. Shirai Y, Ohtani T, Tsukuda K, Hatakeyama K. Radical surgery is justified for locally advanced gallbladder carcinoma if complete resection is feasible. Am J Gastroenterol 1997; 92: 181–2. 37. Ogura Y, Mizumoto R, Isaji S, Kusuda T, Matsuda S, Tabata M. Radical operations for carcinoma of the gallbladder: present status in Japan. World J Surg 1991; 15: 337–43. 38. Nakamura S, Sakaguchi S, Suzuki S, Muro H. Aggressive surgery for carcinoma of the gallbladder. Surgery 1989; 106: 467–73. 39. Maibenco DC, Smith JL, Nava HR, et al. Carcinoma of the gallbladder. Cancer Invest 1998; 16: 33–9. 40. Cubertafond P, Gainant A, Cucchiaro G. Surgical treatment of 724 carcinomas of the gallbladder: results of the French Surgical Association Survey. Ann Surg 1994; 219: 275–80. 41. Yamaguchi K, Chijiiwa K, Saiki S, et al. Retrospective analysis of 70 operations for gallbladder carcinoma. Br J Surg 1997; 84: 200–4. 42. Ouchi K, Owanda Y, Matsuno S, Sato T. Prognostic factors in the surgical treatment of gallbladder carcinoma. Surgery 1987; 101: 731–7. 43. Tsukada K, Hatakeyama K, Kurosaki I, et al. Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage. Surgery 1996; 120: 816–21.
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ET
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19. Fong Y, Brennan MF, Turnbull A, et al. Gallbladder cancer discovered during laparoscopic surgery. Potential for iatrigenic tumor dissemination. Arch Surg 1993; 128: 1054–6. 20. Jones RS. Surgery for cancer of the gallbladder and extrahepatic bile ducts. In: Blank KI, Karakousis CP, Copeland EM, eds. Atlas of surgical oncology. Philadelphia: Saunders, 1995: 439–54. 21. Ogura Y, Tabata M, Kawarada Y, Mizumoto R. Effect of hepatic invasion on the choice of hepatic resection for advanced carcinoma of the gallbladder: Histologic analysis of 32 cases. World J Surg 1998; 22: 262–7. 22. Bartlett DL, Fong Y, Fortner JG. Long term results after resection for gallbladder cancer. Implications for management. Ann Surg 1996; 224: 639–46. 23. Baer HU, Metzger A, Glattli A, Klaiber C, Ruchti C, Czerniak A. Subcutaneous periumbilical metastasis of a gallbladder carcinoma after laparoscopic cholecystectomy. Surg Laparosco Endosc 1995; 5: 59–63. 24. Pezet D, Fondrinier E, Rotman N, Guy L, Lemesele P, Chipponi J. Parietal seeding of carcinoma of the gallbladder after laparoscopic cholecystectomy. Br J Surg 1992; 79: 230. 25. Nally C, Preshaw RM. Tumor implantation at umbilicus after laparoscopic cholecystectomy for unsuspected gallbladder cancer. Can J Surg 1994; 37: 243–4. 26. Lundberg O, Kristofferson A. Port site metastasis from gallbladder cancer after laparoscopic cholecystectomy. Results of a Swedish survey and review of published reports. Eur J Surg 1999; 165: 215–22. 27. Gagner M, Rossi RL. Radical operation for carcinoma of the gallbladder. Present status in North America. World J Surg 1991; 15: 344–7. 28. Fong Y, Hefferman N, Blumgart LH. Gallbladder carcinoma discovered during laparoscopic cholcystectomy. Cancer 1998; 83: 423–7. 29. Wanebo HJ, Castle WN, Fechner RE. Is carcinoma of the gallbladder a curable lesion? Ann Surg 1982; 195: 624–31. 30. Jones DB. Carcinoma of the gallbladder. Surg Clin N Am 1990; 70: 1419–28.
REVIEWS
D
Laparoscopic cholecystectomy and unsuspected gallbladder cancer
TE
F. Romano, C. Franciosi, R. Caprotti, S. De Fina, G. Porta, G. Visintini and F. Uggeri Department of General Surgery, San Gerardo Hospital, II University of Milan – Bicocca
AC
Gallbladder cancer is a relatively uncommon malignancy. Its presentation is similar to that of gallstone disease and sometimes with non-specific symptoms. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall gallbladder cancers have a poor prognosis, despite surgery or adjuvant therapies. However, in selected cases, a favourable outcome can be expected and the less favourable predicted outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted post-operatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope. 2001 Harcourt Publishers Ltd
R
Key words: gallbladder neoplasms; laparoscopic cholecystectomy; neoplasm seeding; reoperation; unsuspected carcinoma.
ET
INTRODUCTION
R
Gallbladder cancer (GBC) is the fifth most common neoplasm of the digestive tract, and is found in approximately 1.5–3% of cholecystectomy specimens.1–2 In about only 10–20% of patients is GBC suspected pre-operatively;3–6 in the rest diagnosis is made at the time of surgery or post-operatively by the pathologist. In such cases the surgeon is left with the decision of how to proceed with management of the patient. Usually the management is based on TNM stage of the gallbladder cancer (Table 1),7,8 though factors such as grade and histological morphology could have prognostic relevance. Pre-operative diagnosis of GBC depends on clinical suspicion and careful review of radiological work-up.
Correspondence to: Fabrizio Romano, Department of General Surgery, San Gerardo Hospital, II University of Milan – Bicocca, Via Donizetti 106, 20052 Monza, Italy. 0748–7983/01/030225+04 $35.00/0
Symptoms noted in 50–60% of cases are right upper quadrant pain, nausea, vomiting and anorexia, while weight loss and fatigue are less common.9 Often GBC is associated with a change in previously stable lithic symptomatology10 and in 25% there is a presence of an abdominal mass.11 Signs of suspicion at US or CT scan are a mass filling or replacing the gallbladder, thickening of the wall, infiltration of the liver bed and polypoid lesions larger than 10 mm.12–14 If GBC is suspected pre-operatively, open cholecystectomy must be performed to allow complete evaluation of the extension of disease and wide resection if necessary. Initial laparoscopic exploration may be used to evaluate the extent of disease. Because there is not a proven effective adjuvant therapy available for GBC,15,16 the best treatment is complete surgical extirpation of the cancer. The optimal operation is one in which the gallbladder is not disrupted, negative margins are achieved and involved lymphatics are removed.17,18 Since even carcinoma in situ is demonstrated to seed the peritoneal cavity with consequent carcinomatosis if 2001 Harcourt Publishers Ltd
226
REVIEWS
Regional lymph nodes N1 Tumour in cystic, pericoledochal or hilar lymph nodes N2 Tumour in peripancreatic, periduodenal, coeliac or superior mesenteric lymph nodes
T1, T2, T1, T4,
N0, M0 N0, M0 T2 or T3, N1, M0 N2 or M1
R
Stage 1 2 3 4
AC
Distant metastases M1 Distant metastases
ET
gallbladder is violated,19 meticulous detail in dissection must be carried out to avoid disruption of the gallbladder. Even if usually GBC is associated with a limited lymph-node involvement in the area of cystic duct, choledochus, or portahepatis, the surgical dissection involves en bloc removal of the lymph nodes of the coeliac axis, portahepatis, hepatoduodenum ligament, hepatic artery and peripancreatic area. The extent of hepatic resection advocated for a radical surgery varies from resection of the gallbladder bed with 2 cm of hepatic parenchyma (extended cholecystectomy) to anatomic resection with removal of segments IV and V.20–22 Furthermore, because of the tendency for GBC to recur at laparoscopic port sites, excision of the port sites is advocated due to multiple case reports of implantation after LC.23–26 This extended surgery may be performed with expected mortality and morbidity of 0 to 8.5% and 5% to 11% respectively.27,28 In case of gallbladder cancer diagnosed in association with LC four scenarios will be discussed: (1) GBC noted on final pathology after LC; (2) GBC noted after removal of the specimen and opening of the gallbladder at time of surgery; (3) GBC suspected during LC due to difficult dissection; and (4) extensive disease noted on placement of the laparoscope.
R
After completion of an open or laparoscopic cholecystectomy, the specimen should be opened and inspected for mucosal abnormalities. If the gallbladder is not inspected or a pathological process is not identified, GBC may not be diagnosed until after surgery. In this case, the pathological tumour stage (Tx) may be the only information available to guide therapy. If the pathologist analysis reveals a Tis or T1 stage, the prognosis is favourable. If there has been no gallbladder violation, the margins are negative and no signs of intraperitoneal spread are noted, a 5 year survival of 80% to 100% is reported after cholecystectomy alone.29–31 No improvement is noted with a reoperation in this group, so cholecystectomy can be considered curative. If the margins are positive at cystic stump, reoperation and biliary resection is necessary to avoid early recurrence.32 In case of gallbladder perforation (reported in 26–33% of LC),33,34 the problem is one of peritoneal seeding and not local control of the disease. In this case local resection for peritoneal spillage or gallbladder contents, even if advocated by some, is probably not warranted.35 For patients with stage T2, T3 or T4 prognosis is not so good. Recent reports show that 5 year survival for patients with T2 GBC can be improved with extended cholecystectomy from 40% to 90%.36 The survival benefit may be compromised if disruption of gallbladder with tumour spillage occurs at the time of LC. Occasionally long-term survival is noted in patients with T3 or T4 stage, however there is a high likelihood of tumour spillage and subsequent peritoneal carcinomatosis in patients treated with simple cholecystectomy. Over 50% of patients who are candidates for re-exploration with curative intent will have disease precluding R0 resection found at operation.37 Moreover, reoperation and resection for T3 and T4 GBC results in early recurrence with poor 5 year survival.38 However re-exploration may be considered in patients with T3 or T4 disease, because surgical resection offers the only chance for cure. If this is the case, preoperative evaluation of the local extent of tumour, of possible presence of metastatic disease and of the patient’s ability to withstand a major operation must be analysed. To obtain a R0 resection, extended cholecystectomy should suffice in T2 stage, but hepatic resection would be necessary in T3 and T4 patients.
D
Primary tumour Tis Carcinoma in situ T1 Tumour invading mucosa (pT1a) Tumour invading muscle layer (pT1b) T2 Tumour invading the perimuscular connective tissue with no extension beyond the serosa or into the liver T3 Tumour invading beyond the serosa or into adjacent organs (extending 2 cm or less into the liver) T4 Tumour extending more than 2 cm into the liver or two or more adjacent organs
GBC noted on final pathology after laparoscopic cholecystectomy
TE
Table 1 TNM staging system for gallbladder carcinoma
GBC noted at extraction of the specimen during laparoscopic cholecystectomy The gallbladder should be inspected after removal of the specimen at the time of surgery. If a GBC is suspected, a frozen section should be performed. When a GBC is discovered at this time many of the principles previously stated have to be applied. In case of Tis or T1 stage,
REVIEWS
227
REFERENCES
1. Yamaguchi K, Chijiiwa K, Ichimiya H, et al. Gallbladder carcinoma in the era of laparoscopic cholecystectomy. Arch Surg 1996; 131: 981–5. 2. Wibbenmayer LA, Wade TP, Chen RC, et al. Laparoscopic cholecystectomy can disseminate in situ carcinoma of the gallbladder. J Am Coll Surg 1995; 181: 504–10. 3. Donohue JH, Nagorney DH, Grant CS, et al. Carcinoma of the gallbladder. Does radical resection improve outcome? Arch Surg 1990; 125: 237–41. 4. Shirai Y, Yoshida K, Tsukada K, Muto T. Inapparent carcinoma of the gallbladder. An appraisal of a radical second operation after simple cholecystectomy. Ann Surg 1992; 215: 326–31. 5. Yamaguchi K, Tsuneyoshi M. Subclinical gallbladder carcinoma. Am J Surg 1992; 163: 382–6. 6. Wanebo HJ, Castle WN, Fechner RE. Is carcinoma of the gallbladder a curable lesion? Ann Surg 1982; 195: 624–31. 7. Sumiyoshi K, Nagai E, Chijiiwa Y, Nakayama F. Pathology of carcinoma of the gallbladder. World J Surg 1991; 15: 315–21. 8. AJCC Cancer Staging Manual. American Joint Committee on Cancer. 5th ed. Philadelphia: Lippincott-Raven, 1997; pp. 103–8. 9. Piehler JM, Crichlow RW. Primary carcinoma of the gallbladder. Surg Gynecol Obstet 1978; 147: 929–42. 10. De Aretxabala XA, Roa IS, Burgos LA. Curative resection in potentially resectable tumors of the gallbladder. Eur J Surg 1997; 163: 419–26. 11. Silk YN, Douglass HO, Nava HR, Driscoll DL, Tartarian G. Carcinoma of the gallbladder. The Roswell Park experience. Ann Surg 1989; 210: 751–5. 12. Wibbenmeyer LA, Sharafuddin MJ, Wolverson MK et al. Sonographic diagnosis of unsuspected gallbladder cancer: imaging findings in comparison with benign gallbladder conditions. AJR 1995; 165: 1169–74. 13. Itai Y, Araki T, Yoshikawa K, et al. Computed tomography of gallbladder cancer. Radiology 1980; 137: 713–8. 14. Fultz PJ, Skucas J, Weiss SL. Comparative imaging of gallbladder cancer. J Clin Gastroenterol 1988; 10: 683–92. 15. Pitt HA, Grochow LB, Abrams RA. Cancer of the biliary tree. In De Vita VT, Hellman S, Rosemberg SA (eds). Cancer: Principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven, 1997, pp. 1114–28. 16. Douglass HO, Kim SY, Meropol NJ. Neoplasms of the gallbladder. In: Holland JF, Frei E (eds). Cancer medicine. 4th ed. Baltimore: Williams & Wilkins, 1997: 1955–65. 17. Shirai Y, Yoshida K, Tsukada K, et al. Radical surgery for gallbladder cancer. Long term results. Ann Surg 1994; 216: 565–8. 18. Chijiiwa K, Tanaka M. Carcinoma of the gallbladder: an appraisal of surgical resection. Surgery 1994; 115: 751–6.
AC
cholecystectomy is sufficient. Because of the very uncommon involvement of lymph node at this stage, lymph-node sampling is not advocated.39 Extended cholecystectomy for T2 GBC would be expected to improve survival. The surgeon should perform liver bed resection, resection of extrahepatic duct to achieve negative margins. Prior to resection careful inspection should be undertaken to identify eventual contraindication to extended surgery (Table 2). In case of T3 or T4 cancer, the lesion has almost certainly been violated. Also at this stage careful exploration should be performed to assure the possibility of R0 resection.
Gallbladder cancer is uncommon; if it is diagnosed or suspected pre-operatively, open exploration is indicated. Sometimes GBC may be encountered during laparoscopic cholecystectomy. Therapy is guided by the extent of disease. Patients with T1 stage benefit from cholecystectomy alone. Most cases of T2 stage benefit from extended resection. Some patients with T3 or T4 GBC benefit if a R0 resection can be achieved. In general, contraindications to extended surgery include main portal vein involvement, N2 disease, peritoneal carcinomatosis, extraperitoneal metastasis, bilateral hepatic metastasis, local extension precluding an R0 resection and poor patient condition. Principles of surgical therapy for GBC include avoiding gallbladder violation, achieving negative margins and minimizing morbidity in patients with unresectable disease.
D
Peritoneal carcinomatosis Extrahepatic haematogeneous metastases Main portal vein involvement N2 nodal involvement Bilateral haematogenous hepatic metastases Local extension precluding R0 resection Patient physiologically unfit to undergo operation
CONCLUSIONS
TE
Table 2 Contraindications to extended resection for gallbladder cancer
GBC suspected during laparoscopic cholecystectomy
R
ET
R
If GBC is suspected during LC, the procedure should be converted to open one, unless there is extensive disease precluding resection. The surgeon should proceed with an extensive exploration of peritoneal surface, N1 and N2 lymph nodes and liver (eventually with intraoperative ultrasound). In case of question about the ability to achieve negative margins or the need for extended hepatic resection or extended liver involvement, the procedure should be terminated. Survival benefit in patients with lymph-node involvement appears limited to those in whom the lymph node of the cystic duct, common bile duct and porta hepatis are involved.40 If N2 disease is identified, early recurrence is expected.41 Peritoneal carcinomatosis portends a poor prognosis with a median survival reported of 1–3 months.42 When identified in patients undergoing reoperation, it usually results in early failure and subsequent death. Extended resection is not indicated.
Extensive GBC precluding resection identified on initial inspection If extensive disease is noted during abdominal exploration the goal is to document the extent of disease, to confirm the diagnosis with tissue biopsy, and to provide palliation with minimal morbidity. Cholecystecomy, if technically favourable conditions are present, may be undertaken to avoid subsequent gallbladder complications.42
228
REVIEWS
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