Outcome of surgical management of initially irresectable or complicated multiple colorectalliver metastases

Outcome of surgical management of initially irresectable or complicated  multiple colorectalliver metastases

H Said,a MD; Gamal Fawzy,a MD; A Kame[,a MD; K Elhosseny,b MD; Ramy Ghali,b MD; Mohmad Elgharib, b MD; Mohamed Hamdy Attya,c MD; A Abdelaal,a MD; Abdel  Wahab Ezzat,a MD

a) Department of General Surgery,  Ain Shams University, Cairo, Egypt. b) Department of Medical  Oncology, Ain Shams University, Cairo, Egypt.

c) Department of Diagnostic Radiology, Ain Shams University, Cairo, Egypt. d) Department of General Medicine, Ain Shams  University, Cairo, Egypt.

Abstract

Introduction: Hepatic resection is the procedure of choice for curative treatment of colorectal liver metastases  (CLM).l  Hepatectomy allows five-year survival rates up to 58% in selected cases2 and 10 year survival rates of 16%3 to 23%.4 The use of surgical innovations, such as staged resection, portal vein embolization, and repeated resection has allowed higher resection rates in patients with bilobar disease. The use of neoadjuvant chemotherapy  allows up to 38% of patients previously considered irresectable to be significantly  downstaged  and eligible for hepatic resection.2

Design: A prospective study.

Patients: From January 2009 to December 2011, 30 consecutive patients (16 male and 14 female) with multiple colorectalliver metastases (synchronus and metachronus) underwent surgical intervention  in Ain Shams University Hospitals. The mean age was 49.9 years (27 to

75y, SD ±10.31). Simultaneous resection was done when primary lesion was not locally advanced, no intestinal obstruction and the metastases were easily resectable with adequate future liver volume. Neoadjuvant chemotherapy  was started in all metachronus and selected patients with synchronus liver metastases. The aim of neoadjuvant was to downstage irresectable tumors and test their biological behavior. Follow up of patients with clinical examination,  tumor marker and  radiological assessment for  a median follow  up  period  of  12  months was  done.

Results: This study was conducted on 30 patients. Twenty eight patients had adenocarcinoma (93.3%), 1 mucinous adenocarcinoma (3.3%) and 1 liomyosarcoma ofthe  colon (3.3%). LNs were positive in 76.7% and negative in 23.3% of cases.Ninety one colorectal metastatic tumors were identified (synchronous in 9 patients and metachronus in 21 patients) situated in the right lobe, left lobe and bilobar in 53%, 12%, and 35% respectively. CEA was elevated in14 cases and CA19.9  was elevated  in 7 cases. Fifty percent underwent major hepatectomy and 50% underwent minor hepatectomy. The mean postoperative hospital  stay was 9.5 ± 3.13 days. Twenty nine cases required postoperative ICU admission and the mean postoperative ICU stay was 1.8 ± 1.04days. Six patients (20%) had perioperative complications as follows: biliary leak in three cases (10%), intra-abdominal collection in one case (3%), chest infection in one case (3%)  and  pulmonary embolism in  one  case  (3%).  All  these  complications were  treated conservatively. There were no cases of postoperative liver failure. Nine patients  (30%)  had recurrent malignant disease (mean follow up period was 12 ± 8). Recurrence was local (17%), hepatic (6%) or combined local and distant extra-hepatic (6%). Cases with hepatic recurrence were managed  by hepatic  resection  in one case and the other by percutaneous RFA. Two mortalities were reported. The first patient died from extensive myocardial infarction 3 months postoperatively. The second patient died 15 months postoperatively due to respiratory failure from pulmonary metastases.

Conclusion: Surgical resection is the only  potentially curative  treatment of colorectal metastases.Resectability is no longer restricted and durable survival is possible even in patients with multiple  and large metastases. The philosophy is to be more aggressive, tailoring the management plan by multidisciplinary team, and to increase the indications for surgical resection by using one or combination of the following techniques (Portal vein embolization, local ablative techniques, new chemotherapy or staged hepatectomy).

Introduction:

Colorectal carcinoma with hepatic metastases was long considered as an incurable disease. Recent advances in surgical treatment have  substantially improved the  affected patients' prognosis. At first, surgery was only performed  in patients whose hepatic tumor burden  was small.  Currently, however,  the main issue is the feasibility of curative resection of all metastases.Hepatectomy allows 10 year survival rates of 16%3 to 23%.4

Patients and methods: Patient population:

From January 2009 to December 2011,30 consecutive patients with multiple colorectal liver metastases (synchronous and metachronus) underwent surgical intervention in Ain Shams University Hospitals. They were

16 male and 14 female patients. The mean age was 49.9 years (27 to 75y, SD±10.31).Patients with  poor  general  condition, extra-hepatic metastases,  tumors not responding  to down­ staging or inability to preserve adequate liver volume with good blood supply, venous and biliary drainage (even after different modalities to increase liver  volume e.g. portal vein ligation) were  excluded from  this  study.

Preoperative evaluation:

Meticulous clinical assessment of general condition was  done.  Thoracic and  pelvi­ abdominal CT with contrast injection was done to identify the primary tumor (localization, size,  spread  to neighboring organs, nodal extension), liver metastases (uni- or bilobar, number, size, localization, vascular invasion), presence of lung involvement  and detection of any other extra hepatic metastases. When CT was risky (e.g. Iodine allergy) or when CT was normal but there was high suspicion of liver  lesion  (as  increased levels  of  tumor markers) MRI was performed. Laboratory tests including liver functions, bleeding profile were

done. Tumor markers CEA and CA19-9 did not affect the decision but they were important in the follow up and prognosis. Colonoscopy was done for detection of colorectal tumor (primary  or recurrence). As a routine it was repeated before hepatic surgery if the last one was done more than 6 months  before. CT volumetry was done in cases of aggressive resection plans to detect residual liver volume. Future liver remnant of more than 25% was accepted but in cirrhotic  livers  future  liver remnant (FLR) more than 40% was mandatory.

The  work plan was  discussed with multidisciplinary team  including (hepatic surgeon, hepatologist, medical oncologist  & interventional radiologist). Management of multiple colorectalliver metastases entails the use of other  therapeutic modalities before surgery. The  general principle of these modalities is to increase  the residual liver volume and convert the unresectable metastases to resectable ones .The final aim was to achieve complete (RO) resection of all the liver metastases. In all cases of metachronus  liver metastases and some cases of synchronous liver metastases which were irresectable with the primary tuomrs, neoadjuvant chemotherapy was started before planned hepatectomies. The benefits of neoadjuvant therapy were to convert unresectable lesion to resectable  one and to test biological behavior  of the tumors. Any progression on chemotherapy was considered a contraindication for  surgery. Portal  vein embolization was done when  FLR was inadequate and reassessment with volumetric CT was done after 4 weeks. Portal vein ligation was done in synchronous lesion with inadequate FLR  during resection of  the  primary and reassessment with volumetric CT was done after 4 weeks.

In synchronous metastases, combined resection should be planned when possible but it  is  not  recommended in  urgent colonic

resection, locally advanced colorectal carcinoma (CRC) and cases demanding a major hepatic resection.

Operation:

Patients were positioned supine. All cases were done via laparotomy. Either  a hockey stick incision or midline incision was used (xiphisternal extension). Subcostal retractors were used to provide strong retraction  of the costal margin. The laparotomy  began with a thorough examination of the peritoneal cavity to exclude  any peritoneal disease  or pelvic recurrence (when possible). All regional lymph nodes (porta-hepatis and coeliac) were assessed and any suspicious nodes were sent for a frozen section examination. Bimanual  palpation of the liver combined  with intra-operative US examination of the liver allowed confirmation of  the  number, size  and  position of  each metastasis and helped to identify lesions missed on pre-operative imaging.

Liver  resection was either anatomical resection, in which  one or more  complete segments were removed or atypical (wedge) resection. The type of resection performed depended on size, site, number of tumors and relation to vascular and biliary structures. Small superficially located tumors were resected by wedge resection or 'metastasectomy'. Safety margins  of 1Omm were  recommended but safety margins of Smm were accepted. Larger and multiple lesions usually needed anatomical resection. We  used  the  Harmonic Scalpel (Ethicon Endo-Surgery) for liver parenchyma resection.

Patients who presented  with a technically

'easily'  resectable primary tumour and peripherally placed low-volume liver disease were amenable  to synchronous resection  of both primary  and metastatic  liver disease  at the  same procedure, without increased morbidity  or mortality. Those  patients  who presented with large  bowel obstruction and synchronous CRLM had immediate definitive treatment for their  life-threatening colonic emergency (endoscopic stenting, resection with either a stoma or immediate  reconstruction). When resection of the primary  tumour  was more demanding, when  treatment of the primary  required neoadjuvant treatment or

when the liver disease was such an extent that at  least  a hemi-hepatectomy or  more  was required, a planned sequential staged procedure was preferred.

Pathological assessment:

All  specimens were   examined histo­ pathologically to confirm diagnosis of metastatic colorectal carcinoma, accurate assessment of number, site, size (largest), grade, macroscopic or microscopic vascular invasion and safety margin.

Post-operative care  and  follow  up:

Early post-operative, patients were admitted to intensive care unit (ICU) especially if major hepatectomy was done  to ensure close monitoring and adequate analgesia. Blood tests and  serologic liver  function tests were performed during the 1st, 3rd, 5th and 7th days after resection. All patients underwent  an X­ ray chest examination on the 3rd postoperative day, and ultrasonography was performed during the first week after resection. CT abdomen was done when complications were expected and the US failed to diagnose.

After discharge, patients were assessed 4 weeks later.Inthis visit, in addition to physical examination, liver functions and tumor markers were tested. A return of tumor markers to normal (if  previously elevated) served  to confirm that the goal of resection has been achieved. If they did not return to normal, a meticulous search  for treatable tumor  was performed.

Following this postoperative check, patients were seen at 3, 6 and 12 months after surgery. During each of these visits liver functions and tumor markers were assessed and a CT scan of  the  chest, abdomen and  pelvis were performed. Suspicions raised by  patient symptoms, CT findings  or elevated tumor marker required further investigation by MRI or FDG-PET scans.

Results:

This study was conducted on 30 patients with multiple colorectalliver metastases. They included 16 males (53.3%) and 14 females (46.7%).  The mean age for this group study was 49.9 years (ranging from 27 to 75y) with SD ±10.31. The mean follow up period was

12 months.

Criteria of primary tolorectal tumors: Pathological analysis of the colorectal specimens revealed the following: 28 cases were adenocarcinoma (93.3%), 1 mucinous adenocarcinoma (3.3%) and lliomyosarcoma of the colon (3.3%). All specimens were pathologically confirmed with free safety

margms.

LNs involvement of the resected colonic samples was positive in76.7% of cases (n=23) and  negative  in  23.3%  of  cases  (n=7).

70%

Figure(1):Presentation of colorectalliver metastases.

The primary operative management was in the form of major hepatic resection in 50% (n=15) of cases (right hepatectomy in 5 cases, left hepatectomy in 3 cases and central hepatectomy in one case. Combination procedures of right posterior hepatectomy with

Criteria of metastatit fiver lesions:

Nine patients (30%) bad synchronous, and

21 patients (70%) had metachronus colorectal liver  metastases  Figure(l). Ninety  one

colorectal metastatic tumors were identified with a mean size of 4.3±2.5cm (ranging from

2 to 12cm); lesions were situated in the right, left lobes and bilobar in 53%, 12%, and 35% of  the  cases   respectively  Figure(l).

Pre-operative assessment of CEA and CA19.9 showed the following results, 14 patients out of the 30 (47%) patients had

elevated serum levels of CEA and 7 cases

(23%) had elevated serum levels ofCA19.9.

Figure(2):Distribution of liver metastases.

left lateral hepatectomy was done in 3 cases; combination of left lateral hepatectomy with segmentectomy in3 cases).Bisegmentectomy was done in 27% (n=8), and segmentectomy in 23% of cases (n=7) Figure(3).

I   Hepatic resection             I

Mfnor h·epatectomy

(SO%)

I

Rt                     Lt                    Central               Cornblnati             Segment           Bisegrnen hepate          hepatec          hepat:ect:o                 on                       ectorny              tectorny ctorny              t:orny               my (3%)           procedures              (23%)                  (27%) (17%)                            (10%)                                                    (20%)

•

Rt: posterior

hepatectomy

&Lt: lat               hepatectomy

hepatectomy(:LO                         &.segrnent:ectom

%)                                     y {10%)

Figure (3):Algorithm forhepatectomies done in this study.

Synchronous tumors:

Nine  cases (30%) presented with synchronous hepatic metastases. Four cases (13.3%) underwent resection only for the colorectal malignancy in the first laparotomy due to colonic cause like obstruction or hepatic cause like inadequate FLR. Those patients got adjuvant chemotherapy to downstage the liver metastatic disease then underwent hepatic resection.

5 cases (16.7%) ofthem underwentsm:gical

intervention for  the hepatic metastases synchronously. Three cases (10%) underwent definitive  hepatic  resection  and 2 patients

(6.7%) with bilobar liver metastases with inadequate future liver remnant were planned for 2 staged hepatectomies. Both had radical local resection of the primary tumor.One case had intraoperative right portal vein ligation and the other, underwent right portal vein ligation in association with non-anatomical metastat.:eck>my for left lobar metastatic lesions. In the second stage operation, one of the 2 cases had  right hepatectomy with  RO resectability and  adequate liver  remnant volume, while the  other was deemed irresectable Figure(4).

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Figure (4): Algorithm of management of synchronous metastases.

Metachronous tumors:

Twenty one cases (70%) presented with

metachronous hepatic metastatases. The tumor free survival was 20.7 ±15.7months (5 to 60 months).All of them had received preoperative adjuvant chemotherapy with good response in

6()0/o (n=l8).3 patients (10%) shifted to locally ablative therapy due to unavoidable side effects

of  systemic  chemotherapy. Transcatheter Arterial Chemoembolization (TACE) was used successfully in 2 cases (7%) and ultrasound guided Radiofrequency Ablation (RFA) inone case (3%) with considerable decrease in size of  hepatic  metastases then  followed by hepatectomy Figare(5).

21cases vvoth Metachronous tumors

A      a

adjuvant

chemotherap

1 case had us

uided RFA

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2 cases had TACEthen hepatectomy

18 had definitve hepatic resction

Figure(5): Algorithm of management ofmetachronous metastases.

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Post-operative hospital stay:

The mean postoperative hospital stay was

9.5 ± 3.13 days (ranging from, 7 to 23 days). Twenty nine cases required postoperative ICU admission (97%) to achieve strict monitoring

and early detection of any complication.The mean  postoperative ICU  stay  was  1.8  ±

1.04days (ranging  from, 0  to  6  days)

Figures(6,1).

Hospitalstay                                                          ICU stay

3 days   6 days  0 days

3%      3%

•7days

•sdays

•9days

•lOdays

•10·14days

•more than 20days

Figure (6): Postoperative hospital stay.                     Figure (7): Postoperative ICU stay.

Early  postoperative complications: Early postoperative complication was considered with any complication occurring within 30 days from the operation.Six patients (20%) had postoperative complications, the most  common one  was biliary leak  which occurred in three cases (10%). Conservative management in the form ofmaintainedexternal drainage with antibiotics according to culture and sensitivity (C&S)  was effective in the management of all 3 cases. Intra-abdominal

collection occmred in one case (3%) on the

7th postoperative day and was managed by

ultrasound guided pig-tail external drainage

together with antibiotics according to culture and sensitivity. Chest infection was reported inone case (3%) that was successfully treated with antibiotics according to sputum  C&S. Pulmonary embolism occurred in one case (3%),  it was  controlled effectively with conservative measures and  anticoagulant therapy  with low molecular weight  heparin during the hospital stay and then shift to oral warfarin to maintain INR between 2 and 3 for

12  months postoperative. No  cases were

complicated by postoperative liver cell failure. Mortality during  early postoperative period was 0 Figure(8).

•post-operative complications

3

0                                                  0

Figure (8): Post-operative complications.

Recurrence:

Mean follow up period was 12 ± 8 (ranging from 3to37 months). Nine patients (300/o) had recurrent malignant disease, the recurrence was local,  hepatic  or distant extra-hepatic. Hepatic recurrence occurred solely in 2 cases (6%). One  case  was  managed by  hepatic resection and the other by percutaneous RFA. Recurrence of colorectal carcinoma (local) occurred in 5 cases (17%). Combined local and  distant extra-hepatic lesions  in 2cases (6%); both were managed  by chemotherapy with  or  without radiotherapy Figure(9).

Eight cases out of the nine recurrent cases showed re-elevation of serum level of CEA. The two cases of hepatic recurrence showed fast rise of serum CEA.

MortaHty:

A single mortality case was recorded during

the follow-up  period of 12 months, with a 1- year survival  of 97%. This case passed  the earlypost operativeperiodand started toreceive chemotherapy, she  died from extensive myocardial infarction 3 months after  the surgery.

Another case of mortality had been recorded

15 months postoperatively due to respiratory failure  from  pulmonary metastases.

Recurrence

colorectal

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&distant

7%

Figure (9): Distribution ofrecun-ence.

Discussion:

Colorectal cancer  accounts for  the third most common malignancy inwestern countries. More than 75% of all patients  will develop hepatic metastases during the course of disease; up to 25% of them will have liver metastases

at diagnosis.s Malignant  tumors of the liver

were  once considered a lethal disease. Untreated metastatic colorectal carcinoma has a  median survival of  6 to  9  months.6

Improved perioperative outcomes for hepatic resection have resulted in part from a shift from a focus on ''what  comes out" (ie, tumors) to ''what stays in,(ie,liver). Similarly, resectability  is no longer restricted  based on the number, size, or unilaterality of tumors when an adequate  liver remnant will remain after complete resection of tumor-bearing liver. As a result, patients with more  and  larger

lesions undergo resection, including patients

who  require extensive resection of  liver parenchyma, yet durable survival is achieved.7

Based upon  pre-  and  peri-operative assessment, patients are candidates for surgery if they have no non-resectable extrahepatic disease, all liver deposits can be resected with tumour-free margins, and  sufficient liver parenchyma can  be preserved to avoid postoperative liver  insufficiency. Surgical resection is,to date,the only potentially curative treatment  of   colorectal  metastases.8

No existing  treatment other than surgery can  result in  long-term survival, but  only

10-20% of patients with liver metastases fulfill

standard  selection  criteria and are amenable to surgery. As a consequence, the trend is to be  more aggressive and  to  increase the indications for surgical resection. Portal vein

embolization, ablative techniques and chemotherapy may render patients amenable

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to surgery patients who  would  have  been refused some years ago.8

In this study, 30 patients  presented with multiple colorectalliver metastases underwent surgical intervention (33  successful hepatectomies) with  curative intent. The surgery was used as the main line of treatment in all cases;accompanied with other therapeutic modalities when needed. The patients  were followed up postoperatively for a median of

12 months  to assess  the outcome of this approach in terms of incidence of morbidities and   mortalities  in   the   study  period.

The goal of surgery for liver metastases is to remove all the metastatic  sites, if possible with a free clearance margin of 1 em.The type of liver  resection depends  on the size, the number, and the location of the metastases, as well as their relation to the main vascular and biliary pedicles and the volume of the liver parenchyma that  can  be left  in place  after surgery.

In  some cases, the  choice between performing several wedge resections or a major liver  resection removing  all the deposits  at once  can  be difficult. The first  solution preserves more healthy liver parenchyma, but the  cut  section of  the liver  may  be  larger increasing the risk of postoperative hemorrhage or fluid collection. On the other hand, a major liver resection allows a better clearance between twnour deposits and the cut section of the liver, a better control of peri-operative haemorrhage and the recognition of main intrahepatic vessels, but removes more parenchyma with a risk of post-resection hepatic failure and the theoretical risk of promoting the development of dormant liver metastases by the mechanisms involved in  liver  regeneration. In addition, a large resection  may preclude  further treatment in case of intrahepatic recurrence.

Surgeons  generally prefer  good  margins

around  vital  structures, preferably 1Omm. However, it has been known for a while that any margin at all will actually suffice as most liver  metastases are  'pushing' rather  than infiltrative.9

Synchronous colorectalliver metastases: Synchronous colorectalliver metastasis is found in 20% to 30% in patients at the time of initial diagnosis. Surgical management of this

group of patients is controversial and widely debated.  Some authors have reported  higher complication and mortality rates for patients with simultaneous resections. Nordlinger and colleagues reported an operative mortality of

7% of simultaneous resection, compared with

2% with staged resection. A staged operative approach  was therefore recommended, with the liver resection  performed  2 to 3 months after the resection of the primary. The increase in complications in case of staged resection group may be explained by the need for two laparotomies.lO

Simultaneous resection of the primary colon tumor  and  hepatic metastasis is  safe  and efficient in treating patients with synchronous colorectal metastasis. The overall complication rate is lower for simultaneous  resection than that for staged resection, mortality rate is the same,  and  the  length of  hospital stay  is significantly less. Because it avoids a second laparotomy and reduces complications; simultaneous resection  of the colon primary tumor and  liver metastases should be considered the preferred treatment for suitable patients with resectable synchronous colorectal metastasis. Because effective adjuvant therapies exists  for colorectal cancer, a simultaneous resection also provides for prompt completion of surgical  therapy  and earlier  initiation of adjuvant therapy in this group of patients with high risk of additional  microscopic  diseases who  are  most  likely  to benefit from  such adjuvant therapy.ll

Many authors suggest that if a synchronous hepatic lesion is small, peripherally  located, and easily removed at the time of primary resection with  negligible increase in the morbidity or mortality of the surgery, it is best to do so. In the fortunate circumstance that this proves to be the patient's only hepatic lesion, this would spare  the morbidity of a second laparotomy after an interval reevaluation.12

In this study, 9 cases of synchronous liver metastases were operated on. They were investigated  and assessed well. Five of them underwent surgical intervention for the hepatic metastases with  the colectomy in the same laparotomy, 3  cases  underwent definitive hepatic resection and two cases of synchronous colorectalliver metastases had their first step

of surgical  hepatic  management during  the first   laparotomy. First, had  left   lateral hepatectomy and right portal vein ligation, the other  case  had  portal  vein  ligation alone.

Methods of increasing resectability:

One  of  the  main causes of CRLM irresectability was technically irresectable tumor  (impossible to achieve a disease-free margin or insufficient hepatic reserve to support postoperative hepatic function). The following strategies may  be  undertaken to  allow  a potentially curative resection for these patient groups.

Adjuvant chemotherapy:

The aim of downsizing chemotherapy is to reduce the size of the tumors.In general, the rationale for using this therapy in the context of irresectable disease  is clear, with overall survival in patients receiving systemic chemotherapy but not  surgery reaching approximately 2 years.13 The  potential to downsize disease, and to convert irresectable disease to resectable, is even more intriguing. Adam et al14 reported being able to achieve downsizing to enable resection in 13% of 1,104 patients initially having irresectable metastases, with good outcomes (5-year overall survival of 33% and 5-year  disease  free survival  of

22%); this population included patients having extrahepatic disease. Results achieved  with downsizing through chemotherapy for initially irresectable liver-only disease are even more encouraging, with up to 44% of patients being able to proceed  to complete resection after chemotherapy.15 Although chemotherapy can cause liver toxicity, numerous studies have shown that hepatic resection after chemotherapy is safe  in properly selected patients. Although few reports suggest that intra-arterial therapy may lead to downsizing to enable resection, hepatic arterial infusion (HAl) has not been used widely, possibly due to technical issues with regard to delivery of the  therapy. As salvage for  systemic chemotherapy failure, HAl   holds some promise.16

In this study, 83% of the cases received downsizing chemotherapy. Ninety two percent of those  patients who received downsizing chemotherapy responded well with considerable decrease in  the  size  of  the

metastases and increase in the anticipated future liver volume These results were biased by patients' selection  due to exclusion  of non­ responding patients,

Two-stage resection:

Adam et al. have suggested using two-stage hepatectomy to convert  non-resectable liver

metastases into potentially curable cases. This strategy is usually applied to multinodular bilobar metastases. The frrst-stage resection is intended to remove the highest possible number of tumour lesions. This is followed by a liver regeneration period. During  this period  the patient is usually treated with chemotherapy to limit disease growth.It is recommended that this chemotherapy  should start 3 weeks after surgery (so that it does not interfere with initial regeneration) and continue  for 2-3 months, when  a further set  of assessment tests  are performed in order to evaluate the patient for the second curative stage. The second stage is only performed if it is potentially curative and only if enough parenchymal hypertrophy has occurred  to reduce the risk of postoperative liver  failure. Furthermore, in order  for the patient to be eligible for two-stage hepatectomy, the tumour should be downstaged or stabilized by initial neoadjuvant chemotherapy. The objective  of this technique  is to avoid post­ hepatectomy liver failure. Long-term results from this strategy are still awaited, but initial evaluation of a small series suggested a 3 year survival of35% and a perioperative mortality risk of 15%.17

In this study, 2 patients with synchronous multiple, bilateral CRLM  with  inadequate future liver remnant were planned for 2 staged hepatectomies; in the first stage,  both  had radical local resection of the primary tumor; one case received intraoperative right portal vein ligation, the other, underwent right portal vein ligation in association with non anatomical resection  for a Lt lobe metastatic  lesions. In the second stage operation, one of the 2 cases had Rt hepatectomy with RO resectability and adequate liver remnant volume, while the other was deemed irresectable.

The operative mortality for major hepatic

resections has declined with improved operative techniques and postoperative care, but morbidity remains significant. Operative

mortality ranged from 0% to 7%, and causes of death included hemorrhage, sepsis, and hepatic failure. Morbidity was between 22% and 39%, and common causes of morbidity included hemorrhage, biliary leak or fistula, hepatic failure, perihepatic abscess, wound infection, pneumonia, and  myocardial infarction.IS

In our study, this was no cases of peri­ operative mortalities, that may be due to proper patients selection depending on :MDT decision.

As regard morbidities, (20%) of this study

group  patients had major postoperative complications, the most common one was the biliary leak which occurred in three cases (10%), they were diagnosed clinically  and conservative treatment was successful in the

3 cases. Intra-abdominal collection occurred inone case (3%) that was treated by ultrasound guided aspiration under umbrella of anttbiotics, chest infection in one case (3%) that was successfully treated  with  antibiotics and pulmonary embolism in one case (3%) that was treated conservative with anticoagulant therapy (starting with low molecular weight heparinthen oral warfarin for 1year).No cases of posthepatectomy liver failure occurred, this might be due to proper assessment of risky patients by volumetric liver studies, using nee­ adjuvant chemotherapy to decrease the size of metastases and applying surgical techniques like portal vein ligation and two staged hepatectomies inselected cases.

Recurrence can occur in as many as 60% of  patients following liver  resection of colorectal metastatic disease, with the most frequent site of recurrence being the liver. In approximately 20% of these patients the liver may be the only site of recurrence and as a result these patients may be suitable for re­ resection. The vast  majorities of these recurrences occur in the first two years and for that reason frequent surveillance with CT is critical for early detection. This becomes even more important ifwe consider that the reported morbidity and mortality rates, as well as overall survival rates after re-resection, are similar to those reported for the initial hepatectomy, despite the  potentially greater technical difficulty. In  the  current cost  conscious environment, the fact that intensive 3-monthly CT surveillance detects  recurrence  that is amenable to further resection ina considerable number of patients,leads to significantly better survival for these patients with a reasonable cost per life-year gained.19

In our study, the incidence of recurrence was 300/o. Nine patientshadrecurrent malignant disease, the recurrence was local, hepatic or distant extra-hepatic. Recurrence was distributed as the following; local recurrence of colorectal carcinoma occurred in 18% of cases; hepatic recurrence occurred in 6% of cases (one managed by re-hepatic resection and the other by RFA) and combined both local and distant extra-hepatic lesions in 6% of cases. These cases were managed by chemotherapy.

Figure(10): Multiplecolorectalliver metastases.

Figure(11): Synchronous colorectalliver metastases.This patient had left hemicolectomy + resection of 2metastases in segments HI& IVa+ligationof Right PV.

Figure (12): Left lobe liver metastases. This patient had other metastases in segment 7 in the right lobe.

Figure (13): CT scan showing multiple colorectalliver metastases.

References:

1- Reinhart  T Grundmann: Current state of surgical treatment of liver metastases from colorectal cancer. World J Gastrointest Surg 2011;3(12): 183-196.

2- Evangelos P Misiakos, Nikolaos P Karidis,

Gregory Kouraklis:Current treatment for colorectal liver metastases. World J Gastroenterol2011; 17(36): 4067-4075.

3- Vigano L, Ferrero A, Lo Tesoriere R, Capussotti L:Liver surgery for colorectal metastases: Results after 10  years  of followup. Long-term survivors, late recurrences, and  prognostic role  of mOibidity. AnnSurgOnco/2008; 15:2458-

2464.

4-  Pulitano C, Castillo F, Aldrighetti L, Bodingbauer M,  Parks RW,  Ferla G,

Wigmore SJ, Garden  OJ: What  defines

'cure' after liver resection  for colorectal metastases? Results after 10 years of follow­ up. HPB (Oxford) 2010;  12: 244-249.

5- Taylor 1:Liver metastases from colorectal cancer: Lessons from  past  and  present clinical studies. Br JSurg 1996; 83:456-

460.

6- Khatri VP:Metastatic colorectal carcinoma: pushing the surgical envelope of cure. Ann Surg Onco/2005; 12:866-867.

7-  Abdalla EK:  Surgical management of colorectal liver  metastases. Community Oncology. Volume  6/Number 8.2009.

8- Penna C, Nordlinger B: Surgery  of liver

metastases from colorectal cancer: New promises; British Medical Bulletin 2002;

64:127-140.

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