From Couinaud to molecular biology: the seven virtues of hepato … · 2017. 1. 14. · describe...

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EDITORIAL From Couinaud to molecular biology: the seven virtues of hepato-pancreato-biliary surgery Jean-Nicolas Vauthey, Giuseppe Zimmitti & Junichi Shindoh Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence Jean-Nicolas Vauthey, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA. Tel: +1 713 792 2022. Fax: +1 713 745 1921. E-mail: [email protected] It is an immense honour and a privilege to serve as President at the 12th Annual Meeting of the Americas Hepato-Pancreato-Biliary Association (AHPBA). This presentation is dedicated to those young and old who continue to be passionate students of hepato- pancreato-biliary (HPB) disorders. The talk is a tribute to Claude Couinaud, a French surgeon, and his passion for liver anatomy (Fig. 1). It is also about the crossroads between his and our passion for HPB surgery. In trying to identify the best term to describe these seven crossroads between Couinaud’s world and today’s world, I first thought of using the terms essentials, prin- ciples or reasons, but they sounded too detached and impersonal. I also considered using the terms passions, loves or elations, but I found them to be too emotional. So I chose the term virtues, which is used in ancient and modern philosophy, in psychology, and in many religious traditions (Table 1). Knowledge of liver anatomy The first virtue is of course knowledge of liver anatomy. Couinaud was 30 years old when he began to study the liver with corrosion casts. His early work described precisely the anatomy of the liver based on hepatic veins. He was the first to coin the word sector based on planes of hepatic veins. Couinaud spent his mornings with Henri Mondor and would focus on research in the afternoon. Couinaud was well prepared to understand the vascular distribu- tion of the liver as he had investigated lung anatomy with Phillip Allison in Leeds, England. In 1954, he first described eight liver segments, in La Presse Médicale (Fig. 2). 1 The work of Couinaud is summarized in his book Le Foie (Fig. 3), a true summa hepatica. 2 The book is divided into sections on portal, biliary and hepatic arterial anatomy, and includes the anatomy of other species, such as rhinoceroses and giraffes, and the embryology of the liver. Half of the book summarizes hepatic resection techniques. 3 Respect and credit to mentors The second virtue is giving respect and credit to your mentors. In 1888, 9 years before James Cantlie, Hugo Rex clearly described the main plane of the liver and the four hepatic sectors in an original article on the liver anatomy of the suckling. 4 (Fig. 4) Couinaud said of Rex: ‘I have nothing to add to his description of the portal anatomy of the liver’. Couinaud also insisted on calling the Glisson sheath the Walean sheath because it was described by Walaeus in 1640, 2 years before Glisson had described it (Fig. 5). 5 As I stand here, in the role of AHPBA president, I do so with respect for my predecessors. Each of them contributed enor- mously to the development of HPB surgery (Table 2). As stated by Reid Adams during last year’s presidential address, ‘It was the dream of our founders’.Today we are indebted to the past Presi- dents for their ongoing support of the association and foundation. Surgical technique The third virtue is recognition of an excellent surgical technique as being essential. The field of surgical technique advances in waves, and timely contributions are essential. In 1952, Jean-Louis Lortat-Jacob performed the first extended right hepatectomy in the West with a so-called controlled technique: ligating individual inflow vessels. 6 The same year, Couinaud described the first left hepatectomy with primary ligation of the left Walean sheath. 7 This work paved the way for multiple subsequent descriptions of the sheath technique in Europe, Japan and Australia. Couinaud’s ana- tomical studies prefigured important advances in liver surgery. In 1956, Jacques Hepp and Claude Couinaud described the end-to- side technique of a hepaticojejunostomy. 8 This technique is still used by many surgeons to maximize the mucosal surface of the Presidential Address presented at the Annual AHPBA meeting, Miami, 7–11 March 2012. DOI:10.1111/j.1477-2574.2012.00502.x HPB HPB 2012, 14, 493–499 © 2012 International Hepato-Pancreato-Biliary Association

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EDITORIAL

From Couinaud to molecular biology: the seven virtues ofhepato-pancreato-biliary surgeryJean-Nicolas Vauthey, Giuseppe Zimmitti & Junichi Shindoh

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

CorrespondenceJean-Nicolas Vauthey, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe

Boulevard, Unit 1484, Houston, TX 77030, USA. Tel: +1 713 792 2022. Fax: +1 713 745 1921. E-mail: [email protected]

It is an immense honour and a privilege to serve as President at the12th Annual Meeting of the Americas Hepato-Pancreato-BiliaryAssociation (AHPBA). This presentation is dedicated to thoseyoung and old who continue to be passionate students of hepato-pancreato-biliary (HPB) disorders. The talk is a tribute to ClaudeCouinaud, a French surgeon, and his passion for liver anatomy(Fig. 1). It is also about the crossroads between his and ourpassion for HPB surgery. In trying to identify the best term todescribe these seven crossroads between Couinaud’s world andtoday’s world, I first thought of using the terms essentials, prin-ciples or reasons, but they sounded too detached and impersonal.I also considered using the terms passions, loves or elations, but Ifound them to be too emotional. So I chose the term virtues, whichis used in ancient and modern philosophy, in psychology, and inmany religious traditions (Table 1).

Knowledge of liver anatomy

The first virtue is of course knowledge of liver anatomy. Couinaudwas 30 years old when he began to study the liver with corrosioncasts. His early work described precisely the anatomy of the liverbased on hepatic veins. He was the first to coin the word sectorbased on planes of hepatic veins. Couinaud spent his morningswith Henri Mondor and would focus on research in the afternoon.Couinaud was well prepared to understand the vascular distribu-tion of the liver as he had investigated lung anatomy with PhillipAllison in Leeds, England. In 1954, he first described eight liversegments, in La Presse Médicale (Fig. 2).1

The work of Couinaud is summarized in his book Le Foie(Fig. 3), a true summa hepatica.2 The book is divided into sectionson portal, biliary and hepatic arterial anatomy, and includes the

anatomy of other species, such as rhinoceroses and giraffes, andthe embryology of the liver. Half of the book summarizes hepaticresection techniques.3

Respect and credit to mentors

The second virtue is giving respect and credit to your mentors. In1888, 9 years before James Cantlie, Hugo Rex clearly described themain plane of the liver and the four hepatic sectors in an originalarticle on the liver anatomy of the suckling.4 (Fig. 4) Couinaudsaid of Rex: ‘I have nothing to add to his description of the portalanatomy of the liver’. Couinaud also insisted on calling the Glissonsheath the Walean sheath because it was described by Walaeus in1640, 2 years before Glisson had described it (Fig. 5).5

As I stand here, in the role of AHPBA president, I do so withrespect for my predecessors. Each of them contributed enor-mously to the development of HPB surgery (Table 2). As stated byReid Adams during last year’s presidential address, ‘It was thedream of our founders’. Today we are indebted to the past Presi-dents for their ongoing support of the association and foundation.

Surgical technique

The third virtue is recognition of an excellent surgical techniqueas being essential. The field of surgical technique advances inwaves, and timely contributions are essential. In 1952, Jean-LouisLortat-Jacob performed the first extended right hepatectomy inthe West with a so-called controlled technique: ligating individualinflow vessels.6 The same year, Couinaud described the first lefthepatectomy with primary ligation of the left Walean sheath.7 Thiswork paved the way for multiple subsequent descriptions of thesheath technique in Europe, Japan and Australia. Couinaud’s ana-tomical studies prefigured important advances in liver surgery. In1956, Jacques Hepp and Claude Couinaud described the end-to-side technique of a hepaticojejunostomy.8 This technique is stillused by many surgeons to maximize the mucosal surface of the

Presidential Address presented at the Annual AHPBA meeting, Miami, 7–11

March 2012.

DOI:10.1111/j.1477-2574.2012.00502.x HPB

HPB 2012, 14, 493–499 © 2012 International Hepato-Pancreato-Biliary Association

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anastomosis after bile duct injuries. Mike Farnell and the MayoClinic group reported excellent results with the technique in1999.9 In 1989, Couinaud described the loose precaval spacebetween the vena cava and the liver,10 which Jacques Belghiti laterused to perform the hanging manoeuver.11 The technique is nowutilized for the anterior approach to the large right upper quad-rant tumours.12

In anyone’s career, true captains command respect for theirtechnical skills and clinical judgment. For me, three captains withthese attributes stand out: John C. Bowen, a technically superbsurgeon; Leslie H. Blumgart, a generous and enthusiastic leader;and Edward M. Copeland, a Southern gentleman who gave me aunique understanding of surgery in the cancer patient.

Research focus

The fourth virtue is research focus. Couinaud focused his researchon anatomic variants of liver anatomy. In his 111 casts, 23% ofpatients did not have a right portal vein.10 The variants includeportal vein trifurcations, staged divisions and the absence ofportal vein bifurcation, all of which may markedly increase thedifficulty of major liver resections (Fig. 6). Not described inCouinaud’s work is the very rare total absence of a hepatic portal

Figure 1 Claude Couinaud working with his collection of liver castsat the school of medicine in Paris, 1988. Reprinted with permissionfrom Sutherland and Harris (2002)3

V. sagittale

Secteurparamédian D.

V. sus hépatique D.

Veine sus hépatique G.

D

II

IIIIV

VIII

VVI

VII

Secteur paramédian G.

Secteurlatéral D.

Sect. latéral G.

D

P

P

G

G

Face supérieure

Figure 2 Liver segments described by Couinaud. Adapted from La Presse Médicale, 19541

Table 1 The seven virtues of HPB surgery

1. Knowledge of liver anatomy

2. Respect and credit to mentors

3. Surgical technique

4. Research focus

5. Sharing of knowledge and expertise

6. Team building

7. Translational research

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vein. Patients with this variant have a large hepatic artery. Thisvariant is often associated with hepatic neoplasms.13

This is in contrast with the consistency of the proximal leftportal vein and bile duct, which are present in most patients. Only2% of patients have no left hepatic duct (Fig. 7). This left-sidedregularity is the basis for surgical procedures such as the Hepp-Couinaud hepaticojejunostomy8,9 and portal vein bifurcationresection with left-sided venous reconstruction in patients withKlatskin tumours as proposed by Peter Neuhaus in Germany.14

Couinaud’s research was mainly descriptive, focusing on thefrequency of anatomic variations. AHPBA has advanced the fieldwith consensus conferences relating to hepatocellular carcinoma

(2004 and 2010), pancreas cancer (2008) and colorectal livermetastases (2006 and 2012), and is now organizing Patient CareGuidelines meetings, with the first such symposium, on deep veinthrombosis, held during this 2012 annual meeting. Nevertheless,much remains undone in the field of research. As a next step,AHPBA should prioritize registries and multicentre studies thatwill advance the field.

Sharing of knowledge and expertise

The fifth virtue is sharing knowledge and expertise. In 1975, DrCouinaud retired. In 2000, Eddie Abdalla and I visited him in his

Figure 3 Cover of Le Foie. Études Anatomiques et Chirurgicales, 19572

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upscale apartment in the XVI arrondissement of Paris. To ouramazement, he had continued to work and had self-publishedfour more books between his retirement and 1999.10,15–17

Couinaud welcomed us into his apartment filled with antiques.We had many questions. Our first question was, ‘How did youcome up with the segment numbers? Were they numbered accord-ing to the Paris sections?’ The answer was, ‘Absolutely not. It allcame from Rex’. Couinaud went on to pull the coloured litho-graph from Rex’s original article (Fig. 8).4

Our second question regarded the caudate lobe. In the late1990s, Couinaud had proposed a new segment IX consisting ofthe caudate process and paracaval caudate.18 Papers reportingsegment IX had even been published in major journals and atmeetings of academic societies, such as the French Academy ofSurgery. The problem was that there was no defined portal triadinflow for this new segment IX. Should we really consider a newsegment IX? Without real evidence to support the new segment,Claude Couinaud, in a gesture of great intelligence, retracted theconcept of segment IX and wrote with us a paper that defined,once and for all, segment I as a single segment.19

Couinaud’s work opened a new world to surgeons; his followershave since further advanced the field. The earliest Couinaud fol-

lower in the West was Henri Bismuth, who published SurgicalAnatomy and Anatomical Surgery of the Liver in 1982.20 In 2000,Steven Strasberg proposed a universal nomenclature for resectionthat would eliminate the word lobectomy from our vocabulary andreplace it with right hepatectomy and left hepatectomy; he alsocoined the word section to describe a surgically resectable ana-tomical structure.21 In the East, one of the less well-known follow-ers of Couinaud, Ken Takasaki, has published a remarkabletreatise of surgical technique based on the Walean approach.22

Figure 4 The main plane and the sectoral anatomy of the liver wereclearly described by Rex (1888)4

Figure 5 Walean sheaths as depicted by Couinaud. Adapted fromLe Foie. Études Anatomiques et Chirurgicales. 1) The hilar approach.2) The extrahepatic division of a segmental branch can also involvea branch for an adjacent segment. 3) The hilar plate. 4) Right para-median pedicle sheath. 5) Penetration via the right portal fissure. 6)The peripheral sheath approach involves pedicle structures dedi-cated to a specific segment. Reprinted with permission2

Table 2 AHPBA presidents and their major developments in HPBsurgery

J. Michael Henderson – Distal splenorenal shunt

William C. Meyers – Laparoscopic cholecystectomy

Henry A. Pitt – Cholangiocarcinoma

Steven M. Strasberg – Bile duct injuries

C. Wright Pinson – Liver transplantation

Theodore N. Pappas – Advanced teaching in HPB surgery

Sean J. Mulvihill – Outcome studies in HPB surgery

Bruce D. Schirmer – Fellowship training and accreditation

Mark P. Callery – Laparoscopic evaluation in HPB

W. Scott Helton – Staging and treatment of hepatocellularcarcinoma

Reid B. Adams – Hepatic ultrasonography

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Team building

The sixth virtue is team building. Couinaud teamed up withothers in his office and hunted with his dog Rama during his freetime. The officers of AHPBA teamed up at the 2010 meeting of theInternational Hepato-Pancreato-Biliary Association (IHPBA) inArgentina. It was a turning point for AHPBA. The association wasrenamed: American was changed to Americas to better indicatethat AHPBA is a regional association for the entire continent. Theofficers decided that Postgraduate Courses would be held everyother year in South America. We initiated on-site collaborationswith our Southern colleagues.

There was not much snow for the first Postgraduate Course inChile in July 2011, but the course was well attended. The highlightof the course was the invocation of the newly created ChileanChapter of AHPBA with its officers Xabier de Aretxabala, NicolásJaruffe and Mario Uribe. Other highlights of this year included thetrips organized by the officers to Nicaragua, the Bahamas, CostaRica and Ecuador (Table 3). Gazi Zibari joined me for the on-sitecollaboration to Nicaragua, a country of 6 million with one liversurgeon and only two interventional radiologists. William Jarna-gin led the team to Costa Rica. Their host, Efrain Cambronero,organized the 2nd Costa Rican Gastrointestinal Oncology Con-gress. The team performed a combined bile duct resection with apartial hepatectomy for hilar cholangiocarcinoma.

This brings me to the larger team, the core of our association:the Executive Council. So many talented individuals have contrib-uted countless hours. The leadership team seems too big for some.But no, there is a lot to do and most is undone. We continue tolook for abilities and availabilities.

Translational research

The seventh and last virtue is translational research. Couinauddefined the functional units of the liver but left an open field forthe next generation. Five years ago, I thought we should leavemolecular biology to our children. But the future is now. The goalis not to compete with basic scientists, but basic science shouldanswer questions relevant to HPB practice. Many mutations maypredict the efficacy of chemotherapy. Today, KRAS is the onlymutation used by clinicians to predict a response to anti-EGFRantibodies. In colorectal liver metastases, the main question relates

Figure 6 Absence of the right portal vein: anatomical variants (1989).Reprinted with permission10

Figure 7 Hepatic duct confluence: anatomical variants (1957).Adapted from Le Foie. Études Anatomiques et Chirurgicales2

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to margin width. Should it be 10 mm or less? The answer is2–4 mm based on two studies analysing not only KRAS but mul-tiple somatic mutations in the tissue surrounding the tumour.23,24

Recently, systematic analysis of gene mutations has become fea-sible with novel techniques such as mass spectrometry. Thesetechniques may help us analyse multiple somatic mutations.25

Molecular biology may help us refine predictors of survival afterresection of colorectal liver metastases. In a recent analysis ofsomatic mutations in a small number of patients, mass spectrom-etry identified mutations in 10 of 40 patients undergoing resec-tion. The prognosis was markedly different in patients with no

Table 3 AHPBA onsite collaborations 2011–2012

– Nicaragua – Dec. 2011 (GB Zibari, SH Wei, JN Vauthey)

– Bahamas – Dec. 2011 (E Dixon, SP Cleary, AJ Moser)

– Costa Rica – Feb. 2012 (WR Jarnagin, M D'Angelica, A Hemming,P Allen)

– Kurdistan of Iraq – Mar. 2012: AHPBA + ICS + WSF (GB Zibari,HB D'Agostino, M Moore, B Enderson, B Townsend)

– Ecuador – Apr. 2012 (WC Chapman, DM Nagorney, JA Lowell, BPoulose)

Figure 8 Vascular anatomy as depicted by Rex (1888).4

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mutations and patients with one or more mutations (MDAnderson Cancer Center, unpublished data). HPB translationalresearch, tying basic research with patient care, will be exciting. Incolorectal liver metastases, the future may include molecular evi-dence for surgical procedures and peri-operative intervention(Table 4).

Conclusion

Claude Couinaud passed away in 2008. His remains lie almostanonymous in Bagneux cemetery: no marble, no epitaph, noflowers – just a name and two dates. I suggest an epitaph based ona quotation from one of Couinaud’s books:10,26

We are like dwarves sitting on the shoulders of giants.We see more things than the ancients did and see farther,but this is not effected by the keenness of our sight nor our ownheight: this is because they carry us elevated on the top of theirgigantic height.Bernard de Chartres (? -1124)

Acknowledgement

The authors particularly thank Ruth J. Haynes and Stephanie Deming for

editing.

Conflicts of interest

The authors have no conflict of interest.

References

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l'architecture anatomiques et chirurgicale du foie. Presse Med 62:709–

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2. Couinaud C. (1957) Le foie. Études anatomiques et chirurgicales. Paris:

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3. Sutherland F, Harris J. (2002) Claude Couinaud: a passion for the liver.

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4. Rex H. (1888) Beiträge zur Morphologie der Säugerleber. Morph Jahrb

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9. Murr MM, Gigot JF, Nagorney DM, Harmsen WS, Ilstrup DM, Farnell MB.

(1999) Long-term results of biliary reconstruction after laparoscopic bile

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14. Neuhaus P, Jonas S, Bechstein WO, Lohmann R, Radke C, Kling N et al.

(1999) Extended resections for hilar cholangiocarcinoma. Ann Surg

230:808–818.

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hepatic Bile Ducts: Anatomical and Technical Study. Paris: C Couinaud.

16. Couinaud C. (1999) Tell Me More about Liver Anatomy. Paris: C

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17. Couinaud C. (1991) Controlled Partition of the Liver for Transplantation.

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18. Filipponi F, Romagnoli P, Mosca F, Couinaud C. (2000) The dorsal

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Hepatogastroenterology 47:1726–1731.

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Anatomy and Resections. HPB 2:333–339.

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Table 4 Translational research in HPB surgery: future perspectives

Surgical procedures based on molecular evidence

– Predict regeneration and safety of an extended procedure?

– Anatomic or non-anatomic resection?

– Surgical margins for various diseases?

Peri-operative chemotherapy based on molecular evidence

– Prediction of effectiveness?

– Prediction of toxicity?

– Patient selection?

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