Surgical Oncology

Liver and Pancreas Surgery

Bernardo Franssen M.D.

Changes in Management of Select Cancer Scenarios

Disclosures

• No conflict of interest

• Nothing to disclose

Specialist and SubspecialistDifferent point of view

Surgeon Oncologist

Radiation Oncologist

Anesthesiologist

Primary Care

Whole – Environment – Family

* Multidisciplinary Conferences

Overview

• Three topics where the management paradigm has shifted since most of us trained.

1) Pancreas Cancer treatment strategy

2) Metastatic Colorectal Cancer to Liver

3) Minimally Invasive Surgery – Specifically of the Liver and Pancreas.

Goals

• Be part of a comprehensive team that provides great care and gives hope to patients

• Identify patients who might benefit from these evolving strategies

• Timely referral to a specialist (or several): multidisciplinary approach

Pancreatic Cancer

Quick Overview

• Ductal adenocarcinoma

• 55,000 new cases/yr USA

• Mets to LN, liver, peritoneum, lung are common

• Only 15-20% are resectable at time of presentation

• Surgery prerequisite for cure

Quick Overview

• 20% of the unresectable cases are locally advanced at presentation.

- arteries are involved (SMA, celiac artery)

- other organs (stomach, aorta, vena cava)

• Borderline resectable: < 50% of an artery is abutted, or a vein is taken or abutted.

* On triple phase CT scan, Endoscopic Ultrasound and / or MRI.

Classic Clinical Scenario

• 67 M smoker

- Worsening diabetes (2 months)

- 15 pound weight-loss and loss of appetite.

- Painless Jaundice

CA-19-9: 405, expected alterations in LFT’s, rest of labs are normal

CT abdomen with IV/Contrast

What we used to do

• If good functional status:

Resection ASAP!

• Otherwise: Palliative Gemcitabine

What were the outcomes of surgery?

• 20-30 % aborted surgeries due to peritoneal or liver mets

• Another 20% Unresectable

• High rate of marcoscopic and microscopic positive margins ( as high as 60%)

• Early recurrence (R1,R2)

• Many patients never got adjuvant chemotherapy after surgery. Specially if complications

Foundation for Neoadjuvant Therapy

• Newer more effective regimens

• Response rates: in the 23-30% range compared to Gemcitabine 5-7%. (triple!)

• Survival doubled compared to Gemcitabine alone. (6 months to 11.3 months)

N Engl J Med. 2011;364(19):1817. N Engl J Med. 2013;369(18):1691

Neoadjuvant ProtocolsBorderline

• Why not give the chemotherapy and maybe even radiation before surgery?

• Conditions needed to proceed as per NCCN guidelines.

– Need a pathologic diagnosis (EUS guided biopsy is preferred)

– Long term (up to 6 months) biliary decompression

What's the Rationale

• Improve the selection of patients for whom resection will not offer a survival benefit

• Increase rates of margin-negative resections. Major goal of surgery!

• Early treatment of micrometastatic disease.

Current Results

• No Randomized controlled trials.

• Series proving substantial benefit

MD Anderson series:

- 160 patients

- 125 Completed neoadjuvant therapy

- 79 remained resectable after chemo or chemo-rads

- 66 were resected

- 62 had negative margins. (38% of original cohort)

- Median Survival:: 20 months. - if resected 40 months - if not resected 11 months.

- 5 year survival: 36% (In those that completed therapy)

- 27 patients remain free of disease at last check (Cured?)

Katz,et al. J Am Coll Surg. 2008;206(5):833. Epub 2008 Mar 17.

Best case scenario in pancreas cancer

✓ You never have metastases (tumor biology)

✓ Your tumor responds well to a multidrug chemo regimen (before or after surgery)

✓ You get a complete resection with negative margins (R0 resection)

✓ Your CA-19-9 normalized after treatment

>40% chance of 5 year survival and possibly cure!

Colorectal Cancer

with Liver Mets

Quick Overview

Colon Cancer: second cause of cancer death in both genders

In 2014 there were 130,000 cases diagnosed

The most common site of metastasis is the liver

1/3 of patient present with liver only disease.

Classic Clinical Scenario

• 64 year old male

• Presents to you with several months of constipation and reduced caliber stools, weight-loss and is anemic.

• Staging CT with multiple liver lesions on the right and three on the left. No extra-hepatic disease.

Who you gonna call ?

• Oncologist, Colorectal Surgeon, Liver surgeon.

• If colonic obstruction – Colorectal surgeon first

• Otherwise Oncologist first (chemo is a given) and liver and colorectal surgeon close second.

• Timing of procedure is individualized

Liver metastasis: What we used to do

• 20 years ago: Stage IV disease =

Palliative Chemo

• Much better chemo treatments (still not great)

- 5 year OS: 10% with 1/5 sustained response

Liver metastasis: What we used to do

• 15 years…. And if we take it out? Yes but….

- Unilobar disease only

- Resection margin > 1cm

- No pulmonary mets

- Adequate liver remnant volume

- Synchronous lesions only

Resectability today

• Tumors that can be resected completely, leaving an adequate liver remnant.

– Can be bilobar

– Can be multiple lesions

– No size restriction

– Can be combined with Radiofrequency ablation

– Can be after liver remnant growth from Portal Vein Embolization (PVE)

– Can have lung mets (when resectable)

Outcomes

• Mortality < 5%

• Five year survival average 40% (11% with best chemo regimen) 4X!

• Well selected patients

• Adequate chemo

• Right timing

Portal Vein Embolization

Hypertrophy

Combine with otherloco-regional treatments

• Radiofrequency ablation

• Y-90: Beads of radiation injected selectively through the hepatic artery

• Maybe: Chemoembolization (TACE): Occludes arterial flow to tumor

Radiofrequency Ablation (RFA)

Yttrium-90 in CRLM

• General Principles.

Aim: “selectively target all tumor in the liver with high doses of radiation regardless of the cell of origin or location yet limiting radiation of the normal liver to tolerable levels”

FDA approved in combination with chemotherapy.

- More complete response

- Same survival

Kennedy, Am J Clin Oncol 2012;35:91-99

Conclusion

• Best chance of cure with CRLM to liver is with effective chemotherapy and surgical removal .

4X more 5 year survival than chemo alone!

• Send patient to Liver Surgeon / Surgical Oncologist early for planning and best timing

MIS ≠ Specialty

The Brave

• Early 90’s

• No formal training

• Limited specialized equipment

• High conversion rate

• Resistance / Controversy

• Questionable results.

Gagner M et al. Laparoscopic partial hepatectomy for liver tumor (abstract) Surg Endosc. 1992;6:99.

Gagner M, Pomp A. Laparoscopic pylorus-preserving pancreatoduodenectomy.Surg Endosc. 1994;8:408–10

PubMed search on Laparoscopic Surgery

0

50

100

150

200

250

300

350

1997 2007 2017

Pancreas

Liver

Updated: 2017

The value of minimal access surgery in the staging of patients with potentially resectable peripancreatic malignancy. Brennan, Ann Surg 1996

Early experience with laparoscopic resections of islet cell tumors Gagner, Surgery 1996

Laparoscopic fenestration in polycystic liver disease. Belghiti, Br J Surg 1996

Minor Procedures

BenignTransition

Major Procedures

Cancer

Minor Procedures

BenignTransition

Major Procedures

Cancer

Pancreaticoduodenectomy with Major Vascular Resection: a Comparison of Laparoscopic Versus Open Approaches. Kendrick, Ann Surg 2014

Laparoscopic robot-assisted versus open total pancreatectomy: a case-matched study. Mosca, Surg Endosc 2014

Laparoscopic parenchymal-sparing liver resection of lesions in the central segments: feasible, safe, and effective. Conrad, Surg Endosc2014.

Number of Laparoscopic Whipplesby Year of Publication

Boggi, et al. Surg Endosc (2014) ahead of print Aug 15

MIS: Standard of Care in HPB

• Distal Pancreatectomy

• Lateral Sectionectomy

Mesleh, et al. J Hepatobiliary Pancreat Sci (2013) 20:578–582

Buell, et al. Ann Surg 2009;250: 825–830

When did your Institution Begin Performing MIS Hepatectomies?

46%

27%

10%

9%

8%

448 HPB Surgeons

2009-

2004-2008

1999-2003

-1998

No Lap

Hibi. et al. J Hepatobiliary Pancreat Sci (2014) 21:737–744

Percentage of Hepatectomies Done Minimally Invasive

27%

29%

28%

13%

3%

448 HPB surgeons

< 10%

11-20%

21-40%

41-80%

>80%

Hibi. et al. J Hepatobiliary Pancreat Sci (2014) 21:737–744

World Report on MIS Liver Surgery

Nguyen, Ann Surg 2009;250: 831–841

Open vs. Laparoscopic

Farges, Ann Surg 2014;260:916–922)

Reality Check

World Report on MIS Liver Surgery

Nguyen, Ann Surg 2009;250: 831–841

International Consensus2008 Louisville

• Experience in HPB surgery and MIS essential

• Equivalent or improved outcomes for minor resection (Except VII, VIII)

• Caution for major resections or posterior resections

• Laparoscopy as the standard for lateral sectionectomy

Buell, Ann Surg 2009;250: 825–830

International Consensus

2014 Morioka

• Equivalent or improved outcomes in both major and minor resections. (Publication bias, low level of evidence)

• Lateral Approach for posterior tumors

• Caution for major resection although feasible.

Wakabayashi, Ann Surg 2015;261:619–629

Laparoscopic Liver Surgery

Advantages

- CO2 Pneumoperitoneum likely reduces venous bleeding

- Visualization and reach through the caudal approach

Disadvantages

- Loss of tactile sensation

- Restricted capacity to manage bleeding.

- Need for specialized equipment

Wakabayashi, Ann Surg 2015;261:619–629

J Hepatobiliary Pancreat Sci (2014) 21:723–731

Technology Driven Operation

Mbah, et al. HPB 2012, 14, 126–131

• Staplers • US • Indocyanine injection / Infra-red light• Sophisticated 3D imaging assessment

• Transection devices– Clamp Crushing – Ultrasonic Dissection, Water Jet, Harmonic Scalpel,

Ligasure, Tissue-Link, Radiofrequency-assisted liver transection.

• Surgeons Choice

Lap vs. Open Hepatectomy

Variables 1 2 3 4 5 6 7 8 9 10

11

12

13

14

15

16

17

Complication rate X X X X X X X X = X X X X X =

EBL X X X X X X X X = X X X X X =

Tranfusion X X X X X X = X X X

Duration of Surgery X = X X = X = X = X

Negative Margins X = = = X

3 yr OS = = = = = = =

Hospital Stay X X X X X X X X X X X X X X X =

Costs X X X X X =

Wakabayashi, et al. J Hepatobiliary Pancreat Sci (2014) 21:723–731

Favors Laparoscopic Hepatectomy: X Favors Open Hepatectomy: X

Lap Resection for Colorectal Mets

Nguyen, et.al. Ann Surg 2009;250: 842–848 Wei, Annals of Surgical Oncology, 2006, 13(5): 668)676

Benign vs. Malignant Disease

Farges, Ann Surg 2014;260:916–922)

Reality Check

Cost Analysis

Tsinberg, Surg Endosc (2009) 23:847–853

Conclusion

Minimally Invasive Liver Surgery

• Its feasible and safe in expert hands

• Offers clear advantages: EBL, Hospital stay, Minor Complications.

• Equivalent oncologic results and costs

• Major Resections should only be performed by experts in specialized centers

• Lacking level I evidence

Thank you!