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THE LARGEST WESTERN EXPERIENCE WITH HEPATOPANCREATODUODENECTOMY: LESSONS LEARNED WITH 35 CASES

Abstracts

Background

: Hepatopancreatoduodenectomy is one of the most complex abdominal operations mainly indicated in advanced biliary carcinoma.

Aim

: To present 10-year experience performing this operation in advanced malignant tumors.

Methods

: This is a retrospective descriptive study. From 2004 to 2014, 35 hepatopancreatoduodenectomies were performed in three different institutions. The most common indication was advanced biliary carcinoma in 24 patients (68.5%).

Results:

Eighteen patients had gallbladder cancer, eight Klatskin tumors, five neuroendocrine tumors with liver metastasis, one colorectal metastasis invading the pancreatic head, one intraductal papillary mucinous neoplasm with liver metastasis, one gastric cancer recurrence with liver involvement and one ocular melanoma with pancreatic head and right liver lobe metastasis. All patients were submitted to pancreatoduodenectomy with a liver resection as follows: eight right trisectionectomies, five right lobectomies, four left lobectomies, 18 central lobectomies (IVb, V and VIII). The overall mortality was 34.2% (12/35) and the overall morbidity rate was 97.4%.

Conclusion

: Very high mortality is seen when major liver resection is performed with pancreatoduodenectomy, including right lobectomy and trisectionectomy. Liver failure in combination with a pancreatic leak is invariably lethal. Efforts to ensure a remnant liver over 40-50% of the total liver volume are the key to obtain patient survival.

Pancreatic Neoplasms; Hepatectomy; Pancreatectomy


Racional

: Hepatoduodenopancreatectomia é uma das operações abdominais mais complexas indicadas principalmente no carcinoma biliar avançado.

Objetivo

: Apresentar experiência de 10 anos executando esta operação em tumores malignos avançados.

Métodos

: Trata-se de estudo descritivo e retrospectivo. De 2004 a 2014, 35 hepatopancreatoduodenectomias foram realizadas em três diferentes instituições. A indicação mais comum foi carcinoma biliar avançado em 24 pacientes (68,5%).

Resultados

: Dezoito tinham câncer de vesícula biliar, oito tumores de Klatskin, cinco tumores neuroendócrinos com metástase hepática, uma metástase colorretal invadindo a cabeça do pâncreas, uma neoplasia mucinosa papilar intraductal com metástase hepática, uma recorrência do câncer gástrico com comprometimento hepático e um melanoma ocular com metástase na cabeça do pâncreas e no lobo direito do fígado. Todos os pacientes foram submetidos a duodenopancreatectomia com ressecção hepática da seguinte forma: oito triseccionectomias direitas, cinco lobectomias direitas, quatro lobectomias esquerdas, e 18 lobectomias centrais (IVb, V e VIII). A mortalidade global foi de 34,2% (12/35) e a taxa de morbidade global foi de 97,4%.

Conclusão

: Alta mortalidade é vista quando grande ressecção hepática é realizada junto à duodenopancreatectomia, incluindo lobectomia e triseccionectomia direita. Insuficiência hepática em combinação com deiscência do pâncreas é invariavelmente letal. Esforços para garantir fígado remanescente em 40-50% do volume total são a chave para obter sobrevida.

Neoplasia pancreática; Hepatectomia; Pancreatectomia


INTRODUCTION

Hepatopancreatoduodenectomy (HPD) is a highly complex abdominal operation mainly used to treat advanced biliary carcinoma that includes gallbladder cancer and perihilar cholangiocarcinoma. In the western countries, it is in known as a "Japanese operation", and only few centers have developed interest in performing such major interventions in the treatment of very limited malignancies. Japanese specialized centers developed an enormous expertise in HPDs and delineated their role in treating advanced biliary carcinomas55. Ebata T, Watanabe H, Ajioka Y, Oda K, Nimura Y. Pathological appraisal of lines of resection for bile duct carcinoma. Br J Surg 2002; 89: 1260-7.,1818. Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nimura Y. Evolution of surgical treatment of perihilar cholangiocarcinoma. Ann Surg 2013; 258: 129-40.,2222. Sakamoto E, Nimura Y, Hayakawa N, Kamiya J, Kondo S, Nagino M, et al. The pattern of infiltration ate the proximal border of hilar bile duct carcinoma: a histologic analysis of 62 resected cases. Ann Surg 1998; 227:405-11..

Advances in imaging technology over the last decade led to early diagnosis of gastrointestinal tumors. Patients, who do not share that fortune, typically present with jaundice and vascular encasement. The gallbladder cancers disseminate to local and distant lymph nodes by a richly drained submucosal layer of the biliary tree, especially at the body of the gallbladder, and by veins through the gallbladder fossa to intrahepatic portal branches of segment IV, V and VIII. The perihilar cholangiocarcinoma usually grow radially and locally with fewer distant disseminations routes such as those seen in gallbladder carcinomas1010. Igami T, Nagino M, Oda K, Nishio H, Ebata T, Yokoyama Y, Shimoyama Y. Clinicopathologic study of cholangiocarcinoma with superficial spread. Ann Surg 2009; 249: 296-302..

Liver failure, pancreatic leakage and sepsis are the most catastrophic complications after HPDs. Prevention of these complications by systematic application of portal vein embolization, biliary drainage, bile replacement and preoperative nutritional optimization are of paramount importance33. Ebata T, Kamiya J, Nishiro H, Nagasaka T, Nimura Y, Nagino M. The concept of perihilar cholangiocarcinoma is valid. Br J Surg 2009; 96:926-34.

The aim of this study was to present the results with this complex procedure, which represent the largest Western experience.

METHODS

This study was approved by the Ethics Committee of the Rio de Janeiro Adventist Hospital, Rio de Janeiro, RJ, Brazil

From March 2004 to September of 2014, 35 consecutive HPDs were performed in three institutions in Brazil. A retrospective analysis was based on chart revision. Most of the patients had advanced biliary cancers (68.5%) and all cases were performed by an experimented senior surgeon.

Procedures

All procedures include major liver resections (at least three segments) and pancreatoduodenectomy. The surgical approach always started with the pancreatoduodenectomy followed by the liver resection, mainly because vascular reconstructions were frequently applied (48.5%) and because the liver transection becomes easier without the pancreatoduodenal block. For biliary cancer an en-block specimen was always preferred. Indications of HPD are detailed in Table 1.

TABLE 1
- Indications for hepatopancreatoduodenectomy

Were separated those patients who underwent pancreaticoduodenectomy with right hepatectomy (Group 1), right trisectionectomy (Group 2), left hepatectomy (Group 3) and central hepatectomy (Group 4). Reconstruction of the pancreatic stump was made by three different technics: 1) pancreatojejunostomy in seven cases; 2) pancreato-gastrostomy in 17 cases, and 3) pancreatic stump ligation in 11 cases. A standard Roux-en-Y reconstruction of the biliary tree was performed on all cases.

RESULTS

The overall 30-day mortality was 34.2% (12/35), independent of initial hospitalization time. Mortality was especially high in those patients who underwent major liver resections (Group 1 and 2 - Table 2). The most common causes of death were: liver failure as defined by Broek2727. Van den Broek MA, OldeDamink SW, Dejong CH, Lang H, Malago M, Jalan R. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int 2008;28:767-80., followed by abdominal sepsis related to pancreatic leakage, pneumonia, and renal failure. Groups 3 and 4 had lower complications rates and liver failure was not present in any of these patients. However, pancreatic leak was still a significant morbidity in this group.

TABLE 2
- Types of liver resections on hepatopancreatoduodenectomies

Twenty-three patients who survived the surgical intervention and were discharged from the hospital, 11 cases were lost follow-up over the 10 years of this study. Twelve are alive with up to date follow-up (Table 3). Seven (20%) out the original cohort are alive and free of recurrence at the time of the writing of this report.

TABLE 3
- Patients follow-up

DISCUSSION

HPD was introduced in Japan in the 70´s to treat advanced biliary carcinoma1313. Kasumi F, Tagagi K, Konishi T, Sakamoto G. Surgical treatment of carcinoma of the gallbladder, analyzing its modes of spread (in Japanese). Nippon Shokaki Geka Gakkai Zasshi (Jpn J Gastroenterol Surg) 1976;9: 170-7.,2121. Nishi M, Nemoto T, Misumi A, Nakamura K, NozatoH. Cancer of Gallbladder: A clinical and pathological study of 18 operative cases (in Japanese). Gan no Rinsho (Jpn J Cancer Clin) 1964;10:869-77.,2525. Takasaki K, Kobayashi S, Mutou H, Akimoto S, Toda K, Asado H, Fukushima Y, Yoshikawa T, Imajizumi Y, Satoh Y, Takada T, Nakamura M, Hanyu F, Shinohara M. Our experiences (five cases) of extended hepatectomy for carcinoma of the gallbladder (in Japanese). Tan to Sui (Biliary Tract and Pancreas)1980;7:923-32.. Japanese specialized surgeons have developed significant experience in the surgical management of patients with advanced hepatopancreaticoduodenal cancer11. Araida T, Oshikawa T, Azuma T, Ota T, Takasaki K, Hanyu F. Indications for pancreatoduodenectomy in patients undergoing lymphadenectomy for advanced gallbladder carcinoma. J Hepatobiliary Pancreat Surg 2004;11:45-49.,1414. Makuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 1990; 107:521-7.,1717. Mizumoto R, Ogura Y, Matsuda S, Kusuda T, Taoka H, Kaneda M, Yajlma Y, Tabata M. Cooperative study of surgical treatment of carcinoma of the biliary tract in Japan (in Japanese). Tan to Sui (Biliary tract and Pancreas)1990;11: 869-82.,1919. Nakamura M, Hanyu F, Araida T, Koshikawa T, SuzukiM, Azuma T, Hirano H, Ohta T, Toda H. Pancreatoduodenectomy with hepatic resection (in Japanese). Tan to Sui (Biliary Tract and Pancreas 1992;13:1305-13.,2323. Shinohara T, Mizuno Y, Okada M, Takasaki K, Mutoh H, Yoshikawa T. A patient with advanced carcinoma of gallbladder surviving for 4 years and 6 months, following extended right hepatic lobectomy combined with pancreaticoduodenectomy (in Japanese). Nippon Rinsho Geka Gakkai Zasshi (J Jpn Soc ClinSurg) 1986;47:1656-60.. In the western hemisphere, very few groups are interested in reproducing this experience. So far, only Hemming et al.99. Hemming AW, Magliocca JF, Fujita S, Kayler LK, Hochwald S, Zendejas I, et al. Combined resection of the liver and pancreas for malignancy. J Am Coll Surg. 2010;210:808-14. published a consisted report with HPD in the western countries. Nonetheless, a growing number of surgeons are engaged in developing more expertise with it in this decade. In the southern hemisphere, our groups have the largest HPD experience outside Japan.

Ebata et al.6 6. Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, Nagino M. Review of hepatopancreatoduodenectomy for biliary cancer: an extended radical approach of Japanese origin. J Hepatobiliary Pancreat Sci .2014;21:550-5.define it as a multi-visceral resection combining a major liver resection and a pancreatoduodenectomy, which obtains an en-block specimen that encircles the entire extra-hepatic biliary system. In this study, all types of major liver resections with pancreatoduodenectomy performed simultaneously was called HPD77. Ebata T, Yokoyama Y, Igami T, Sugawara G, Nimura Y, Nagino M. Hepatopancreatoduodenectomy for Cholangiocarcinoma. A Single center Review of 85 consecutive patients. Ann Surg, 2012; 256:297-305.. In 1990´s Japanese reports with it, including Nimura´s initial series with 24 cases and 25% mortality, mainly by liver failure and sepsis2020. Nimura Y, Hayakawa N, Kamiya J, Toda K. Hepatopancreatoduodenectomy for advanced carcinoma of the biliary tract. Hepatogastroenterology. 1991;38:170-5.. Tsukada et al.2626. Tsukada K, Yoshida K, Aono T, Koyama S, Shirai Y, Uchida K. Major hepatectomy and pancreatoduodenectomy for advanced carcinoma of the biliary tract. Br J Surg 1994; 81:108-10. reported seven HPDs with 29% mortality rate. Miyagawa et al.1616. Miyagawa S, Makuuchi M, Kawasaki S, Hayashi K, Kitamura H. Outcome of major hepatectomy with pancreatoduodenectomy for advanced biliary malignancies. World J Surg. 1996; 20: 77-80. in 1996 published 0% mortality in seven cases and routine preoperative portal vein embolization. Shirai et al.2424. Shirai Y, Ohtani T, Tsukada K. Combined pancreatoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma: long term results. Cancer. 1997;80: 2484-92. in 1997 reported 17 cases in stage IV gallbladder cancer and the 5-years survival was 29% and those with R0 resection the 5-years survival was 50%. The authors learned from this series that HPD is a very complex operation and the combination of right lobectomy or right trisectionectomy has a high mortality rate and such procedures requires a mandatory portal vein embolization to ensure a liver remnant large enough to avoid liver dysfunction. Likewise, preoperative biliary drainage and bile replacement are also important tools to guarantee better clinical status. . The so called "Nagoya´s protocol" appears to be instrumental in order to achieve lower postoperative mortality18. The benefits of preoperative biliary drainage and bile re-infusion improving mitochondrial function, promoting adequate liver regeneration and also improving intestinal mucosa immunity to protect against bacterial translocation, has been well documented22. Diamond T, Dolan S, Thompson RL, Rowlands BJ. Development and reversal of endotoxemia and endotoxemia-related death in obstructive jaundice. Surgery. 1990;108:370-4.,1111. Kamiya S, Nagino M, Kanazawa H, Tagaki K, Asahara T, Nimura Y. The value of bile replacement during external biliary drainage; an analysis of intestinal permeability, integrity and microflora. Ann Surg 2004;239:510-17..

Ebata et al.4 4. Ebata T, Nagino M, Nishio H, Arai T, Nimura Y. Right hepatopancreatoduodenectomy: improvements over 23 years to obtain acceptability. J Hepatobiliary Pancreat Surg 2007; 14: 131-5.reported that hepatic failure rates decreased from 56% to 14% after routine preoperative portal vein embolization. In the 2000´s, because portal vein embolization has been widely used in the preoperative management, a lower incidence of liver failure was observed and many reports with zero mortality following HPD. Interestingly, many studies showed a worse survival in gallbladder cancer when compared to cholangiocarcinomas. All this cumulative knowledge has encouraged many eastern surgeons to perform HPD in cholangiocarcinomas with very good results99. Hemming AW, Magliocca JF, Fujita S, Kayler LK, Hochwald S, Zendejas I, et al. Combined resection of the liver and pancreas for malignancy. J Am Coll Surg. 2010;210:808-14.. Ebata et al.1212. Kaneoka Y, Yamaguchi A, Isogai M. Hepatopancreatoduodenectomy: Is it suitable for bile duct cancer versus gallbladder cancer. J Hepatobiliary Pancreat Surg. 2007;14: 142-8. reported a 10-years survival of 32.1% with it for cholangiocarcinomas. Kaneoka et al.1212. Kaneoka Y, Yamaguchi A, Isogai M. Hepatopancreatoduodenectomy: Is it suitable for bile duct cancer versus gallbladder cancer. J Hepatobiliary Pancreat Surg. 2007;14: 142-8. and Miwa et al.1313. Kasumi F, Tagagi K, Konishi T, Sakamoto G. Surgical treatment of carcinoma of the gallbladder, analyzing its modes of spread (in Japanese). Nippon Shokaki Geka Gakkai Zasshi (Jpn J Gastroenterol Surg) 1976;9: 170-7. also reported excellent 5-years survival for HPD in cholangiocarcinomas 52% and 64%, respectively. Wakai, et al.2828. Wakai T, Shirai Y, Tsuchyia Y, Nomura T, Azakawa K. Combined major hepatectomy and pancreatoduodenectomy for locally advanced biliary carcinoma: long term results. World J Surg . 2008;32: 1067-74. in 2008 published 28 cases with perioperative mortality of 21%.

We acknowledge the weaknesses of this report where 11 patients (31.4%) were lost to follow-up. This is mainly related to the public health system in a very large country where patients need to travel long distances to get to specialized centers and many of those patients returned home were advanced medical care is scarce. Only 12 cases (34.2%) had long term follow-up in this series88. Fernandes E, . 26th Meeting of Japanese Society of Hepato-biliary-pancreatic surgery - 11-14 Jun 2014 Wakayama - Japan..

During 10-years period, many improvements and experience were collected in the management of biliary carcinoma by the partners of this study. Using the Nagoya´s team protocol refined our approach to HPD. All the complications observed in this period were the same observed by Japanese surgeons in the 90´s. The combination of right trisectionectomy right lobectomy with pancreatoduodenectomy is feasible but mandatory portal vein embolization is required to obtain good postoperative survival because our results suggest that mortality over 40% is seen in those patients who underwent HPD (Group 1 and 2). So far, long term survival (9-years) was observed only in one patient who underwent right trisectionectomy plus pancreatoduodenectomy and portal vein reconstruction for gallbladder cancer and two patients with complex central hepatectomies plus pancreatoduodenectomy are also free of tumors recurrence in this series. Another four patients are alive and free of disease but the follow-up interval is short.

CONCLUSION

HPD is a complex abdominal operation with a high mortality rate and a long learning curve. We emphasize that this operation should be limited to specialized centers with experience in liver transplantation background and advanced hepatobiliopancreatic surgery. Aggressive preoperative management with biliary drainage and portal vein embolization are crucial maneuvers to obtain satisfactory results. The HPDs for gallbladder cancer is feasible but requires a careful patient selection.

REFERENCES

  • 1
    Araida T, Oshikawa T, Azuma T, Ota T, Takasaki K, Hanyu F. Indications for pancreatoduodenectomy in patients undergoing lymphadenectomy for advanced gallbladder carcinoma. J Hepatobiliary Pancreat Surg 2004;11:45-49.
  • 2
    Diamond T, Dolan S, Thompson RL, Rowlands BJ. Development and reversal of endotoxemia and endotoxemia-related death in obstructive jaundice. Surgery. 1990;108:370-4.
  • 3
    Ebata T, Kamiya J, Nishiro H, Nagasaka T, Nimura Y, Nagino M. The concept of perihilar cholangiocarcinoma is valid. Br J Surg 2009; 96:926-34
  • 4
    Ebata T, Nagino M, Nishio H, Arai T, Nimura Y. Right hepatopancreatoduodenectomy: improvements over 23 years to obtain acceptability. J Hepatobiliary Pancreat Surg 2007; 14: 131-5.
  • 5
    Ebata T, Watanabe H, Ajioka Y, Oda K, Nimura Y. Pathological appraisal of lines of resection for bile duct carcinoma. Br J Surg 2002; 89: 1260-7.
  • 6
    Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, Nagino M. Review of hepatopancreatoduodenectomy for biliary cancer: an extended radical approach of Japanese origin. J Hepatobiliary Pancreat Sci .2014;21:550-5.
  • 7
    Ebata T, Yokoyama Y, Igami T, Sugawara G, Nimura Y, Nagino M. Hepatopancreatoduodenectomy for Cholangiocarcinoma. A Single center Review of 85 consecutive patients. Ann Surg, 2012; 256:297-305.
  • 8
    Fernandes E, . 26th Meeting of Japanese Society of Hepato-biliary-pancreatic surgery - 11-14 Jun 2014 Wakayama - Japan.
  • 9
    Hemming AW, Magliocca JF, Fujita S, Kayler LK, Hochwald S, Zendejas I, et al. Combined resection of the liver and pancreas for malignancy. J Am Coll Surg. 2010;210:808-14.
  • 10
    Igami T, Nagino M, Oda K, Nishio H, Ebata T, Yokoyama Y, Shimoyama Y. Clinicopathologic study of cholangiocarcinoma with superficial spread. Ann Surg 2009; 249: 296-302.
  • 11
    Kamiya S, Nagino M, Kanazawa H, Tagaki K, Asahara T, Nimura Y. The value of bile replacement during external biliary drainage; an analysis of intestinal permeability, integrity and microflora. Ann Surg 2004;239:510-17.
  • 12
    Kaneoka Y, Yamaguchi A, Isogai M. Hepatopancreatoduodenectomy: Is it suitable for bile duct cancer versus gallbladder cancer. J Hepatobiliary Pancreat Surg. 2007;14: 142-8.
  • 13
    Kasumi F, Tagagi K, Konishi T, Sakamoto G. Surgical treatment of carcinoma of the gallbladder, analyzing its modes of spread (in Japanese). Nippon Shokaki Geka Gakkai Zasshi (Jpn J Gastroenterol Surg) 1976;9: 170-7.
  • 14
    Makuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 1990; 107:521-7.
  • 15
    Miwa S, Kobayashi A, Akahane Y. Is major hepatectomy with pancreatectomy justified for advanced biliary malignancy? J Hepatobiliary Pancreat Surg. 2007; 14:136-41.
  • 16
    Miyagawa S, Makuuchi M, Kawasaki S, Hayashi K, Kitamura H. Outcome of major hepatectomy with pancreatoduodenectomy for advanced biliary malignancies. World J Surg. 1996; 20: 77-80.
  • 17
    Mizumoto R, Ogura Y, Matsuda S, Kusuda T, Taoka H, Kaneda M, Yajlma Y, Tabata M. Cooperative study of surgical treatment of carcinoma of the biliary tract in Japan (in Japanese). Tan to Sui (Biliary tract and Pancreas)1990;11: 869-82.
  • 18
    Nagino M, Ebata T, Yokoyama Y, Igami T, Sugawara G, Takahashi Y, Nimura Y. Evolution of surgical treatment of perihilar cholangiocarcinoma. Ann Surg 2013; 258: 129-40.
  • 19
    Nakamura M, Hanyu F, Araida T, Koshikawa T, SuzukiM, Azuma T, Hirano H, Ohta T, Toda H. Pancreatoduodenectomy with hepatic resection (in Japanese). Tan to Sui (Biliary Tract and Pancreas 1992;13:1305-13.
  • 20
    Nimura Y, Hayakawa N, Kamiya J, Toda K. Hepatopancreatoduodenectomy for advanced carcinoma of the biliary tract. Hepatogastroenterology. 1991;38:170-5.
  • 21
    Nishi M, Nemoto T, Misumi A, Nakamura K, NozatoH. Cancer of Gallbladder: A clinical and pathological study of 18 operative cases (in Japanese). Gan no Rinsho (Jpn J Cancer Clin) 1964;10:869-77.
  • 22
    Sakamoto E, Nimura Y, Hayakawa N, Kamiya J, Kondo S, Nagino M, et al. The pattern of infiltration ate the proximal border of hilar bile duct carcinoma: a histologic analysis of 62 resected cases. Ann Surg 1998; 227:405-11.
  • 23
    Shinohara T, Mizuno Y, Okada M, Takasaki K, Mutoh H, Yoshikawa T. A patient with advanced carcinoma of gallbladder surviving for 4 years and 6 months, following extended right hepatic lobectomy combined with pancreaticoduodenectomy (in Japanese). Nippon Rinsho Geka Gakkai Zasshi (J Jpn Soc ClinSurg) 1986;47:1656-60.
  • 24
    Shirai Y, Ohtani T, Tsukada K. Combined pancreatoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma: long term results. Cancer. 1997;80: 2484-92.
  • 25
    Takasaki K, Kobayashi S, Mutou H, Akimoto S, Toda K, Asado H, Fukushima Y, Yoshikawa T, Imajizumi Y, Satoh Y, Takada T, Nakamura M, Hanyu F, Shinohara M. Our experiences (five cases) of extended hepatectomy for carcinoma of the gallbladder (in Japanese). Tan to Sui (Biliary Tract and Pancreas)1980;7:923-32.
  • 26
    Tsukada K, Yoshida K, Aono T, Koyama S, Shirai Y, Uchida K. Major hepatectomy and pancreatoduodenectomy for advanced carcinoma of the biliary tract. Br J Surg 1994; 81:108-10.
  • 27
    Van den Broek MA, OldeDamink SW, Dejong CH, Lang H, Malago M, Jalan R. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int 2008;28:767-80.
  • 28
    Wakai T, Shirai Y, Tsuchyia Y, Nomura T, Azakawa K. Combined major hepatectomy and pancreatoduodenectomy for locally advanced biliary carcinoma: long term results. World J Surg . 2008;32: 1067-74.
  • Financial source: none

Publication Dates

  • Publication in this collection
    Jan-Mar 2016

History

  • Received
    11 Aug 2015
  • Accepted
    10 Dec 2015
Colégio Brasileiro de Cirurgia Digestiva Av. Brigadeiro Luiz Antonio, 278 - 6° - Salas 10 e 11, 01318-901 São Paulo/SP Brasil, Tel.: (11) 3288-8174/3289-0741 - São Paulo - SP - Brazil
E-mail: revistaabcd@gmail.com