From: Subject: KEY ISSUES RELATED TO SURGICAL MANAGEMENT OF TUMORS OF LIVER AND GALL BLADDER AND RELATED RECENT ADVANCES Date: Thu, 28 Sep 2006 10:35:57 +0530 MIME-Version: 1.0 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: file://C:\WINNT\Profiles\Administrator\Desktop\IIfolderonlearningmaterials22.9.2006\surgery\liver_gallbladder.htm X-MimeOLE: Produced By Microsoft MimeOLE V5.00.2314.1300 KEY ISSUES RELATED = TO SURGICAL MANAGEMENT OF TUMORS OF LIVER AND GALL BLADDER AND RELATED = RECENT ADVANCES

Key=20 issues related to surgical management of Tumors of=20 Liver

Biliary=20 tract, Gall bladder and related recent = advances.

By

Dr.=20 Gunna Bhagvanth Reddy

FRCS(Ed),=20 FRCS(Glas)

Consultant=20 Surgeon

E-mail:=20 brgunna@yahoo.co.in

 

Tumors=20 of the liver:

 

Most common = Tumors of=20 the liver are Malignant - primary or secondary. Other less common are = Benign=20 tumors - Cystic or Solid. Most of the Liver tumors are asymptomatic, = with=20 patients having normal liver functions, and they are = increasingly=20 discovered incidentally during routine investigations.

 

Cystic=20 tumors of the Liver:

 

Cystic lesions = of the=20 liver are easily identified by ultrasonography and most of them are = simple=20 cysts. Liver cysts are regarded as congenital malformations = and=20 require no further investigation or treatment, as = complications are=20 rare. Occasionally, simple cysts can grow very large and = produce=20 compressive symptoms. These are managed by limited surgical = excision=20 of the cyst wall (cyst fenestration), which can usually be = done=20 laparoscopically[1,2] or partial liver = resection[3].=20

Solid Tumors = of the=20 Liver:

The most = common solid=20 tumors of the liver are malignant tumors. Hepato-cellular carcinoma is = the=20 primary tumor of the liver and usually occurs in a liver that has been=20 chronically injured by an infection, metabolic diseases or induced by = certain=20 Drugs or Alcohol. In case of malignant tumors of Liver, cure is possible = only if=20 the tumor is entirely removed by surgery or other methods. There is = option of=20 Liver Transplantation, if the tumor has not spread outside the liver.=20

Benign Tumors: =

Benign tumors = are=20 usually asymptomatic, but have to be differentiated from malignant = tumors.=20 Benign tumors may be haemangiomas, liver cell adenomas or focal nodular=20 hyperplasia. Haemangiomas are commonest benign tumors of the liver, with = an=20 incidence of 3% of Liver tumors. Malignant transformation and = spontaneous=20 rupture is rare in these cases and surgical resection is indicated only = for=20 large symptomatic Haemangiomas[4]. Liver cell adenomas are = uncommon=20 tumors of the Liver and there is 10% chance of malignant transformation. = Some=20 times Liver resection is advised to prevent malignant = transformation[5].=20 Focal nodular hyperplasia, on the other hand, is usually asymptomatic = and not=20 pre-malignant and no surgical intervention is necessary. =

 

Malignant=20 Tumors:

 

Primary Liver = tumor,=20 Hepato-cellular Carcinoma is one of the most common malignancies in the = world,=20 with approximately 1,000,000 cases reported every year. This ranges from = 15,000=20 cases in the United States to more than 250,000 in China. About 80% of = people=20 with Hepato-cellular Carcinoma are males and more than 80% of them occur = in=20 patients with Cirrhotic livers. These tumors are also seen in childhood. = Although two-thirds of people have advanced malignant liver disease when = they=20 seek medical help and one third of the patients have malignancy that has = not=20 progressed beyond the liver. The most promising treatments apply to this = latter=20 group.

 

Secondary=20 or Metastatic tumors are common, which occur in healthy Liver and found = in 40%=20 of all patients dying of cancer. Without surgical resection the = five-year=20 survival rate for all patients with liver metastases is zero, compared = with an=20 overall five-year survival after resection of 30%. Patients = most=20 suited for resection are those with fewer than three or four=20 metastases.

In=20 view of treatment, Liver tumors are classified in one of four=20 ways:

  1. Localized=20 and resectable (operable) tumors are found in one place and can be = removed.=20
  2. Localized=20 and unresectable (inoperable) tumors are found in one area but cannot = be=20 totally removed safely.
  3. In=20 advanced cases, cancer has spread throughout the liver and/or to other = parts=20 of the body.
  4. In=20 recurrent cases, the cancer has returned to the liver or another part = of the=20 body after initial treatment.

Surgical=20 options for Liver tumors:

 

The=20 principle of complete tumour removal, however, remains a=20 prerequisite, and one limitation is the need to leave enough = liver to=20 function. This depends both on the extent and distribution of = the=20 tumour burden and the general fitness of the patient and his = or her=20 liver. The liver has an enormous capacity for regeneration. A = fit=20 patient with a healthy liver will regenerate 75% resected Liver within = three=20 months.

 

Surgical = resection is=20 the only treatment that can offer cure. However, owing to = local=20 spread of tumour and severity of pre-existing cirrhosis, such = treatment is feasible in less than one third of patients. = Average=20 operative mortality ranges from 2% to 12% (12% in cirrhotic=20 patients), and five-year survival is around 15%. Surgery on = Cirrhotic=20 livers is risky and may cause liver failure and death. Patients with = primary=20 tumors in Cirrhotic livers should be carefully screened prior to surgery = to=20 diminish these risks. Studies have shown that a normal bilirubin = concentration=20 and other parameters[6] and the absence of clinically significant = portal=20 hypertension measured by hepatic vein catheterization are the best = predictors of=20 excellent outcomes after surgery, with almost no risk for =

postoperative = liver=20 failure. In contrast, the majority of patients with significant portal=20 hypertension will develop postoperative decompensation[7], = (mostly=20 ascites), with a 5-year survival of less than 50%. Patients with = cirrhosis and=20 small (<5 cm) tumors may go for liver transplantation. =

In metastatic = liver=20 tumors, surgical resection is the treatment of choice, ideally combined = with=20 ablation techniques, such as Cryo-ablation or Radio frequency ablation. = In=20 Cryo-ablation, a metal tube is inserted into the tumor while watching = the=20 process with intra-operative ultrasound. The tube is then cooled to = -190=B0C=20 (-360=B0F) and an ice ball engulfs the tumor. The killed tumor is later=20 re-absorbed by the body. In radio-frequency ablation, radio waves are = used, in=20 contrast, heating up the tumor as opposed to Cryo-ablation. The actual = surgical=20 approach used is determined by the findings in the operating room when = the=20 surgeon feels the liver and uses the intra-operative ultrasound. Often = the=20 number of tumors found is greater than the number predicted by CT or MRI = scanning. If all tumors can be removed or ablated during the surgery,=20 approximately 30% of patients can live for 5 years or more. If tumors = recur in=20 the liver after the surgery, a repeat operation or ablation can often be = performed. Even removal of large amounts of tumor is relatively safe and = in the=20 hands of experienced surgeons the mortality is generally less than 2%.=20

Until,=20 late 1970s, surgery to remove primary liver tumors was rarely done. = Operating on=20 the liver is difficult for several reasons. Many of the major blood = vessels=20 running to and from the heart pass behind or through the liver. Also, = the=20 anatomy of the liver is not always obvious from the surface. The organ = itself is=20 large, dense, and delicate, and is covered, in part, by the rib cage. It = tears=20 easily and bleeds profusely when injured. The major = technical=20 challenge of liver resection is control of bleeding during transection = of liver=20 parenchyma. Today=20 at several centers all over the World, highly complex liver operations = are=20 performed with great frequency, success, and safety. Also, recent = improvements=20 in surgical techniques, and use of Harmonic Scalpels[8],=20 Ultrasonographic=20 dissectors, Water jet scalpel, Bipolar diathermy, Argon coagulation,=20 Radiofrequency, the spray pump (Tissomat) for the application of fibrin=20 glue[9], use of = vascular=20 staplers[10], have=20 led to less blood loss during surgery. This results in a quicker and = less=20 complicated patient recovery period. Some investigators have shown that=20 Hepatobiliary surgery can be performed on elderly patients with good = outcomes=20 that are comparable to those of younger patients.

The=20 liver has tremendous capacity to regenerate and up to 80 percent of the = liver=20 can be removed surgically. A new technique, which stimulates = regeneration before=20 surgery, is also being evaluated. The technique is called pre-operative = portal=20 vein embolization[11]. If the Surgeon feels the portion of the = liver=20 remaining after surgical resection would be too small to allow for a = good=20 outcome, they can shift the blood supply to the healthy portion of the = liver=20 before the resection is done. That healthy area grows larger, and when = it=20 reaches sufficient size, then the resection can be=20 performed.

 

Some=20 centers are also pioneering Laparoscopic surgical methods for = Hepatobiliary=20 tumors. This technique is sometimes used to stage or determine the = extent of a=20 cancer, eliminating the need for open exploratory surgery in some = patients. It=20 has also been used to biopsy tumors; or, in selected cases, Laparoscopic = Liver=20 Resection[12]. Since the procedure is less invasive than = traditional=20 surgery, a patient's recovery time is quicker.

Several=20 Surgical treatment options are available for patients with liver tumors. = It=20 depending upon the presence of Cirrhosis, how extensive is the tumor and = the=20 patient's age and general health. Available options are, Liver = Resection=96Various=20 Types (Right or Left Lobectomy, Left Lateral Segmentectomy, Right=20 Trisegmentectomy, Extended left Lobectomy etc.) Radiofrequency Ablation = or=20 Cryoablation[13], Microwave Ablation[14], Unroofing and=20 Marsupialization, Fenestration and Resection, Enucleation, Laser=20 interstitial thermal therapy and Biological therapy[15], and = final option=20 of Liver Transplantation.

 

 

Tumors of the = Biliary=20 Tract:

 

Though it = traditionally=20 refers to the tumors of the biliary tract/duct, today = Cholangio-carcinoma is=20 ambiguously used. The spectrum of Cholangio-carcinoma is best classified = into=20 three broad groups: 1) Intra-hepatic, 2) Peri-hilar, and 3) Distal = tumors. These=20 categories correlate with anatomic distribution and imply preferred = treatment.=20 Management of the biliary tract tumors presents many challenges. = Normally the=20 presentation is similar to non-malignant conditions, making it difficult = to=20 diagnose. In many cases, preoperative histological or cytological = confirmation=20 of the malignancy is not possible.

 

 

Surgical = options for=20 biliary Tract Tumors:

 

Intrahepatic=20 Cholangiocarcinomas (IHC), a malignant epithelial tumor originating from = the=20 intra-hepatic bile ducts, is the second most common primary liver = malignancy.=20 Unlike Hepato-cellular carcinoma, Intrahepatic Cholangio-carcinomas are = not=20 commonly associated with chronic underlying liver disease. Liver = resection may=20 be possible in localised tumors or may need Liver Transplantation in = selected=20 cases.

 

Peri-hilar=20 and Distal Cholangiocarcinomas are treated to clear the biliary tract=20 obstruction. When possible, = surgical=20 removal of the obstruction is the preferred treatment of choice and may = result=20 in cure. Unfortunately, only 10% of patients present with early stage = disease=20 and are considered for curative resection. Intrahepatic and Klatskin tumors = may require=20 liver resection[16], which may not be an option for older = patients=20 with co-morbid conditions. Orthotopic liver transplantation = [17,18], is=20 considered for some patients with proximal tumors who are not candidates = for=20 resection because of the extent of tumor spread in the liver. Liver=20 transplantation may have a survival benefit over palliative treatments,=20 especially for patients with tumors in the initial = stages.

Gall=20 Bladder Tumors:

 

Tumors of the=20 Gallbladder are uncommon and easily missed since the it is hidden behind = other=20 organs in the abdomen. It is more common in women than in men and is = sometimes=20 discovered after the Gallbladder has been removed for some other reason. = Symptoms of Gallbladder tumors may mirror that of other more common = abdominal=20 ailments, and make it difficult to diagnose at an early stage. These = tumors has=20 tendency to spread very early to the Liver because if its close = proximity.=20

 

Surgical=20 Options for Gallbladder Tumors:

 

Surgical = management for=20 Gallbladder tumors depends on the local extension of the tumor. = Laparoscopic or=20 open cholecystectomy is curative if the diagnosis is unknown and the = cancer is=20 diagnosed to be in in situ stage on histological examination of = the=20 specimen. Patients=20 with preoperative findings suspicious for Gallbladder cancer should = undergo open=20 exploration with intent to perform a radical cancer operation as a = primary=20 procedure, if the diagnosis is confirmed intra-operatively[19].=20 Extended=20 cholecystectomy involves excision of the Gallbladder with regional=20 lymphadenectomy combined with excision of the liver substance adjacent = to=20 Gallbladder bed[20,21]. It involves en bloc removal of the = adventitia and contained lymphatics surrounding the bile duct, portal = vein and=20 hepatic artery.=20 The limits=20 of this dissection extend from the nodes behind the first and second = part of=20 duodenum, the head of the pancreas towards coeliac axis and extend = upwards to=20 the base of the liver.

 

The = recommended extent=20 of the liver resection[22] varies from a non-anatomical wedge=20 resection[23], of the Gallbladder bed to formal removal of IVa = and V=20 segments[24], including the Gallbladder fossa and even right = hepatic=20 lobectomy. Wedge excision is apparently less radical, but it is a = non-anatomical=20 and difficult procedure that carries significant risk of fatal bleeding. = In=20 various reports, the extent of wedge varies from 2cm to 5cm from the = margins of=20 the gross tumour. Right Hepatectomy does not prolong survival if tumor = is=20 locally advanced; and segmental liver resection is a better option if = liver=20 resection is at all indicated.

 

 

Conclusion

 

           =20 Most of the Liver tumors are asymptomatic and difficult to = diagnose at an=20 early stage. In high incidence areas, screening programmes may help in = early=20 diagnosis. Surgical resection is the only treatment that can = offer=20 cure and the principle of complete tumour removal, however, remains = a=20 prerequisite. Four advances are related to the organisation of tumor = care,=20 and are as important, in terms of a deliverable improved = outcome,=20 as any recent research findings or new treatments. These four = advances are: the multidisciplinary Liver tumor treatment team;=20 supportive care for Liver patients; definition of treatment = goals;=20 and the status of clinical trials.

 

Multidisciplinary=20 treatment teams specialising in Liver care have been recognised as being = important for optimal tumor care and for improving outcome. The = organisation and=20 delivery of supportive care to patients with Liver malignancy has = improved.=20 Treatment goals should be more clearly defined and various surgical = options=20 should be discussed in advance. Public awareness and understanding of = the=20 clinical trials in Liver diseases, that are driving clinical research = has to be=20 increased. Research has started on potential treatments such as gene = therapy,=20 and cancer vaccines, which may help in preventing malignant Liver tumors = in=20 future.

 

References

 

  1. Zacherl=20 J, Scheuba C, Imhof M, Jakesz R, Fugger R. Long-term results after=20 laparoscopic unroofing of solitary symptomatic congenital liver cysts. = Surg=20 Endosc 2000; 14(l): 59-62.=20
  2. Klingler=20 P J, Gadenstatter M, Schmid T, Bodner E, Schwelberger H G. Treatment = of=20 hepatic cysts in the era of laparoscopic surgery. Br J Surg = 1997;=20 84(4): 438-44.=20
  3. Madariaga=20 J R, Iwatsuki S, Starzi T E, Todo S, Selby R, Zetti G. Hepatic = resection for=20 cystic lesions of the liver.=20 Ann Surg 1993; 218(5): 610-4.
  1. Stavros=20 Gourgiotis, Panagiotis Moustafellos, Apostolos Zavos,  et al. Surgical=20 treatment of Hepatic haemangiomas: A 15-years experience. ANZ = Journal of Surgery Volume=20 76(9)  - September 2006. Page = 792-5. =20
  2. Giovanni=20 Ramacciato,=20 Giuseppe=20 R Nigri, Paolo Aurello, et al. Giant=20 hepatic adenoma with bone marrow metaplasia not associated with oral=20 contraceptive intake:=20 World=20 Journal of Surgical Oncology 2006=20 Aug 25;4(1):58.=20
  3. Schneider=20 PD, Preoperative assessment of liver function. Surg=20 Clin North Am. 2004 Apr;84(2):355-73.=20
  4. Capussotti=20 L, Ferrero A Vigano L, et al. Portal hypertension: contraindication to = liver=20 surgery? World=20 J  Sur .2006=20 Jun;30(6):992-9.=20
  5. Vyhnanek=20 F Denemark L,Duchac V. Technical=20 aspects of the liver resection procedure--options for combinations of=20 individual methods.=20 Rozhl Chir.2006 May;85(5):239-43.[Article=20 in Czech]=20
  6. Treska=20 V.=20 [A=20 technique of liver resection]=20 Rozhl Chir.2003 Aug;82(8):397-402.=20 [Article=20 in Czech]=20
  7. Poon=20 RT.  Recent advances in techniques = of liver=20 resection.  Surg=20 Technol Int.=20 2004;13:71-7.=20
  8. Alan=20 W. Hemming, Alan I. Reed, Richard J. Howard, et al. Preoperative=20 portal vein embolization for extended Hepatectomy. Ann Surg = 2003=20 May;237(5):686-91.=20
  9. Dulucq=20 JL, Wintringer P, Stabilini C, et al. Laparoscopic=20 liver resections: a single center experience.=20 Surg Endosc.2005 Jul;19(7):886-91.
  10. Pearson=20 AS, Izzo F, Fleming RY, Ellis LM, et al. Intra-operative=20 radio-frequency ablation or Cryo-ablation for hepatic=20 malignancies.=20 Am J Surg.1999 Dec;178(6):592-9.=20
  11. Bertram=20 JM, Yang D, Converse MC, et al. A=20 review of coaxial-based interstitial antennas for hepatic microwave = ablation.=20 Crit Rev Biomed Eng, 2006;34(3):187-213.=20
  12. Jain=20 S, Sacchi M, Vrachnos P, Lygidakis NJ, Andriopoulou E. Recent advances = in the=20 treatment of Colorectal Liver Metastasis: Hepatogastroenterology 2005=20 Sep-Oct;52(65):1567-84.=20
  13. Dinant=20 S, Gerhards MF, Rauws EA,et al. Improved=20 outcome of resection of hilar cholangiocarcinoma(Klatskin = tumor).=20 Ann Surg Oncol. 2006 Jun;13(6):872-80. =20
  14. Cherqui=20 D, Tantawi B, Alon R, et al. Intrahepatic=20 Cholangio-carcinoma. Results of aggressive surgical = management.=20 Arch Surg.1995 Oct;130(10):1073-8.=20
  15. Kadry=20 Z, Mullhaupt, B Renner EL, et al. Living=20 donor liver transplantation and tolerance: a potential strategy in=20 Cholangio-carcinoma.=20 Transplantation.2003 Sep 27;76(6):1003-6. =

 

 

 

 

  1. Weiland=20 ST,  Mahvi DM, Niederhuber JE, et = al.=20 Should=20 suspected early gallbladder cancer be treated = laparoscopically?=20 J Gastrointest Surg.2002 Jan-Feb;6(1):50-6; discussion=20 56-7.=20
  2. Muratore=20 A, Polastri R, Capussotti L. Radical=20 surgery for gallbladder cancer: current options.  Eur J Surg Oncol. 2000=20 Aug;26(5):438-43.=20
  3. Bartlett=20 DL, Fong Y, Fortner JG, Blumgart LH, et al. Long-term=20 results after resection for gallbladder cancer. Implications for = staging and=20 management.=20 Ann Surg.1996 Nov;224(5):639-46.=20
  4. Paquet=20 KJ. Appraisal=20 of surgical resection of gallbladder carcinoma with special reference = to=20 hepatic resection.=20 L Hepatobiliary Pancreat Surg. = 1998;5(2):200-6.=20
  5. Varshney=20 S, Buttirini G, Gupta R. Incidental=20 carcinoma of the gallbladder.=20 Eur J Surg Oncol. 2002 Feb;28(1):4-10.=20
  6. Suzuki=20 S Yokoi Y Kurachi K, et al. Appraisal=20 of surgical treatment for pT2 gallbladder carcinomas.=20 World J Surg.2004 Feb;28(2):160-5.