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10.1245/ASO.2005.03.020
Annals of Surgical Oncology 12:298-302 (2005)
© 2005 Society of Surgical Oncology
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Original Article

Incidence of Unsuspected and Treatable Metastatic Disease Associated With Operable Colorectal Liver Metastases Discovered Only at Laparotomy (and Not Treated When Performing Percutaneous Radiofrequency Ablation)

D. Elias, MD, PhD1, L. Sideris, MD1, M. Pocard, MD, PhD1, T. de Baere, MD2, C. Dromain, MD2, N. Lassau, MD2 and P. Lasser, MD1

1 Department of Surgical Oncology, Institut Gustave Roussy, Cancer Center, 39 Rue Camille Desmoulins, 94805 Villejuif Cedex, France
2 Department of Radiology, Institut Gustave Roussy, Cancer Center, 39 Rue Camille Desmoulins, 94805 Villejuif Cedex, France

Correspondence: Address correspondence and reprint requests to: D. Elias, MD, PhD; E-mail: elias{at}igr.fr.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: When patients with resectable colorectal liver metastases (LM) are treated with percutaneous radiofrequency (RF), some unsuspected intrahepatic and extrahepatic metastases, detectable only at laparotomy, might be ignored and left untreated. This would result in a reduced cure rate. Our purpose was to discover the incidence of unsuspected and surgically treatable intrahepatic and extrahepatic metastases discovered at laparotomy.

Methods: The data of 506 patients who underwent a laparotomy and then a hepatectomy for colorectal LM were prospectively collected and retrospectively analyzed. All patients had undergone at least two types of preoperative liver imaging (but no fluorodeoxyglucose-positron emission tomography).

Results: Unsuspected metastases were discovered at laparotomy in 209 patients (41.3%). There were extrahepatic metastases in 82 patients (16.2%), additional LM in 152 patients (30%), and both in 25 patients (4.9%). Liver palpation and intraoperative ultrasound allowed for detecting additional LM in 125 (24.7%) and 48 (9.4%) patients, respectively. All of them were resected. When only the 124 patients who presented with 1 to 3 LM measuring <3 cm in diameter (candidates for percutaneous RF) were considered, the results were similar. Moreover, the incidence of unsuspected metastases was similar when the periods of surgery (before and after January 1996) were considered.

Conclusions: Laparotomy permits discovery of and treatment with a curative intent of unsuspected intrahepatic or extrahepatic metastases in at least one third of patients with classically resectable colorectal LM. This does not support the use of percutaneous RF ablation instead of hepatic resection for this population, because it will result in an important survival decrease.

Key Words: Liver metastases • Colorectal cancer • Hepatectomy • Radiofrequency ablation • Intraoperative ultrasonography


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Considering the increasing number of articles reporting on series of patients with resectable liver metastases (LM) from colorectal cancer treated with percutaneous radiofrequency (RF),1,2 it is questionable whether this new procedure results in a diminished chance of cure for patients. Our surgical experience has taught us that the detection of unsuspected intrahepatic or extrahepatic metastases at laparotomy is not rare. However, these findings do not always mean that curative surgery is impossible: indeed, we reported, as have others,3,4 that multiple and bilateral LM can be resected—sometimes with the assistance of intraoperative RF5,6—and result in a 25% to 35% 5-year survival rate.3,4 Similarly, we reported that the resection of extrahepatic metastases at the same time as hepatectomy resulted in a 20% 5-year survival rate in 111 patients7 and in a 28% 5-year survival rate for the 75 patients who finally underwent a complete R0 resection.8 In this last study, we considered only the patients who underwent a complete surgical resection of the metastatic disease (curative intent). When considering this type of population, one could question whether patients would have diminished cure rates if not treated with a formal laparotomy.

The aim of this study was to discover the incidence of unsuspected intrahepatic and extrahepatic metastatic disease detection at laparotomy, when it is still treatable with curative intent. In other words, our aim was to discover the incidence of patients who would undergo incomplete treatment if treated only with percutaneous RF.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From 1985 to 2003, 506 patients underwent a laparotomy and complete resection of LM from colorectal adenocarcinomas. There were 239 female and 267 male patients. The median age was 56.7 years (range, 16–78 years), and the primary tumor and LM were synchronous in 46% of cases. The preoperative work-up consisted of clinical examination, thoracic computed tomographic scan, carcinoembryonic antigen level determination, complete colonoscopy, and at least two types of liver imaging. Preoperative ultrasonography and computed tomographic scan of the liver were systematic. After 1994, a magnetic resonance imaging scan of the liver was added when the results of these two preliminary examinations were unclear. No fluorodeoxyglucose-positron emission tomography was used in our series.

All patients underwent a laparotomy with thorough exploration of the abdominal cavity, notably in the area of the primary tumor. A meticulous palpation of the liver and then intraoperative ultrasonography (IOUS) with a Toshiba SSA-340A (Toshiba Co., Ltd., Tokyo, Japan) linear imaging system equipped with a PVF-738H (Toshiba Co., Ltd.) linear array probe (5.0–7.0 MHz) were performed. By definition, all 506 patients were hepatectomized and underwent extrahepatic metastatic disease resection if necessary, with a curative intent. Their data were prospectively collected and retrospectively analyzed. Their main characteristics are listed in Table 1Go.


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  		TABLE 1. Characteristics of the 506 hepatectomized patients
 
Data were prospectively recorded in a specific database. The {chi}2 test or Fisher’s exact test, when appropriate, were used for univariate comparisons. Differences were considered significant at P = .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Unsuspected additional metastases were discovered at laparotomy in 209 patients (41.3%). They consisted of extrahepatic metastases in 82 patients (16.2%), additional LM in 152 patients (30%), and both in 25 patients (4.9%; Table 2Go).


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  		TABLE 2. Distribution of preoperatively unsuspected metastases
 
The locations of extrahepatic metastases are listed in Table 3Go. They mainly consisted of moderate peritoneal carcinomatosis, i.e., macroscopic tumorous peritoneal seeding (7.1%), retroperitoneal lymph nodes (2.5%), hepatic lymph nodes (if not extending into the celiac region; 2.3%), and local recurrence of the primary tumor (2.3%). These extrahepatic metastases were resected at the same time as the LM. Peritoneal carcinomatosis was treated with complete cytoreductive surgery followed by immediate intraperitoneal chemotherapy.9–11


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  		TABLE 3. Sites of extrahepatic metastases discovered (and resected) at laparotomy (82 patients among 506 hepatectomized patients)
 
Preoperatively unsuspected LM were discovered in 30% (n = 152) of patients. They were discovered by visual inspection and palpation of the liver in 125 patients (24.7%) and only by IOUS in 48 patients (9.4%). Palpation and IOUS revealed different additional LM in 21 patients (4.1%). The mean size of the additional lesions identified was 1.1 ± .7 cm, and 76 % of these tumors were ≤1 cm.

When considering only the 124 patients presenting 1 to 3 LM, all measuring <3 cm in diameter (eventual candidates for a percutaneous RF ablation), 27 (21.7%) had extrahepatic localizations unsuspected before surgery, and 35 (28.2%) had unsuspected LM. Five sustained new intrahepatic and extrahepatic localizations. Palpation of the liver allowed discovery of the additional LM in 33 of the 35 patients. Thus, the incidence of additional metastases in this group was similar to that in the group of patients who had more than three LM, LM >3 cm in diameter, or both.

The detection rate of extrahepatic metastases was correlated neither with the discovery of additional LM (P = .73) nor with a high number of LM (P = .89). However, additional LM were discovered significantly (P < .001) more frequently in patients who had more numerous LM before surgery: the incidence was 21.3% in the 328 patients with 1 to 3 LM, versus 49.4% in the 178 patients with >3 LM (the size of LM was not taken into account here).

When we considered the timing of surgery (before or after January 1996) to discover whether an improvement in imaging quality over the years would result in a decreased detection rate of additional LM at laparotomy, the results were similar: 30% in the 233 patients operated on before January 1996, versus 32.2% in the 273 operated on after this date. The results were the same for extrahepatic metastases.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
It is noteworthy that additional metastases were discovered at laparotomy in 41.3% of patients who were candidates for resection of colorectal LM. These findings did not hinder any operation, because of an increase in resectability rates due to constant technical improvements in liver surgery12 and constant broadening of surgical indications.7,8,13

Patient selection was performed in two steps. First, at the issue of a preoperative standard imaging, patients had to sustain resectable LM with a curative intent, sometimes with the planned resection of known extrahepatic metastases. Second, after laparotomy, they were finally included when all metastases known and unknown before surgery were deemed resectable and were resected.

It is clear that percutaneous RF ablation of LM in these patients would result in leaving untreated macroscopic tumor deposits in 41.3% of them. This number is not modified when considering only the patients with no more than three LM measuring <3 cm in diameter. Thus, currently, treating potentially resectable LM with percutaneous RF results in incomplete treatment in more than one third of patients in comparison with standard open surgery. Whether this results in a diminished cure rate for patients is harder to discern, but according to our previous studies of patients with intrahepatic plus extrahepatic metastases resected with a curative intent, their 5-year survival rate is 20% to 28% at 5 years.7,8

Additional LM were discovered in 30% of patients. Visual inspection and palpation of the liver allowed us to find most of these new metastases (24.7% of patients) because we always perform them before IOUS. This number is in accordance with other series in the literature. A recent study from the Memorial Sloan-Kettering Cancer Center14 established that among 111 patients evaluated from October 1997 to November 1998, additional hepatic tumors were found in 37 (33%). Twenty-one patients (19%) had new LM identified only by IOUS, whereas 16 (14%) had their LM discovered by palpation.14 Finally, in this series, extrahepatic metastases were discovered at laparotomy in 6.8% of patients. Other studies reported rates of 15.7% and 26%.15,16

Recent studies testing the efficiency of a laparoscopy plus laparoscopic ultrasonography report that they did not match the results of preoperative imaging studies in 33% to 44% of cases.17–19 It is thus clear that a laparoscopic approach allows detecting most preoperatively unsuspected metastases. However, laparoscopy does not allow for manual palpation of the peritoneal cavity, which remains a fundamental gesture in surgery and the only one capable of detecting a peritoneal nodule trapped inside adhesions, a small-sized adenopathy, or an isoechoic LM. Hence, the vast majority of patients with potentially resectable hepatic colorectal metastases do not benefit from laparoscopy.20

Will fluorodeoxyglucose-positron emission tomography permit detection of more metastases during the preoperative period? Currently, it is mainly useful for detecting extrahepatic tumor sites21,22; however, it is considered that for a tumor ≤1 cm, the detection rate of fluorodeoxyglucose-positron emission tomography is only 21%.21 Therefore, it is highly probable that its contribution will be real but limited in this field.

In conclusion, our data, like other current data, do not support the use of percutaneous RF ablation instead of hepatic resection of colorectal LM. Treating patients with resectable LM by RF will result in a marked survival loss.

Received for publication March 15, 2004. Accepted for publication November 30, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Livraghi T, Solbiati L, Meloni F, Ierace T, Goldberg N, Gazell GS. Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection. Cancer 2003;97:3027–35.[CrossRef][Medline]
  2. Oshowo A, Gillams A, Harrison E, Lees WR, Taylor I. Comparison of resection and radiofrequency ablation for treatment of solitary colorectal metastases. Br J Surg 2003;90:1240–3.[CrossRef][Medline]
  3. Bo Yan D, Clingan P, Morris DL. Hepatic cryotherapy and regional chemotherapy with or without resection for liver metastases from colorectal carcinoma: how many are too many?. Cancer 2003;98:320–30.[CrossRef][Medline]
  4. Elias D, Cavalcanti A, Sabourin JC, Pignon JP, Ducreux M, Lasser PH. Results of 136 curative hepatectomies with a safety margin of less than 10 mm for colorectal metastases. J Surg Oncol 1998;69:88–93.[CrossRef][Medline]
  5. Elias D, Goharin A, El Otmany A, et al. Usefulness of intraoperative radiofrequency thermoablation of liver tumors associated or not with hepatectomy. Eur J Surg Oncol 2000;26:763–9.[CrossRef][Medline]
  6. Pawlik T, Izzo F, Cohen DS, Morris JS, Curley SA. Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 2003;10:1059–69.[Abstract/Free Full Text]
  7. Elias D, Ouellet JF, Bellon N, Pignon JP, Pocard M, Lasser P. Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases. Br J Surg 2003;90:567–74.[CrossRef][Medline]
  8. Elias D, Sideris L, Pocard M, et al. Results of R0 resection for colorectal metastases associated with extrahepatic disease. Ann Surg Oncol 2004;11:274–80.[Abstract/Free Full Text]
  9. Elias D, Blot F, El Otmany A, et al. Curative treatment of peritoneal carcinomatosis from colorectal cancer by complete resection and intraperitoneal chemotherapy. Cancer 2001;92:71–6.[CrossRef][Medline]
  10. Elias D, Bonnay M, Puizillou JM, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol 2002;13:267–72.[Abstract/Free Full Text]
  11. Elias D, El Otmany A, Goharin A, et al. Treatment of liver metastases associated with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate intraperitoneal chemotherapy: results in 22 cases. Int J Surg Invest 2001;3:31–6.
  12. Imamura H, Seyama Y, Kokudo N, et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg 2003;138:1198–206.[Abstract/Free Full Text]
  13. Elias D, Rougier P, Mankarios H, Fahrat F, Lasser P. Resectable liver metastases and synchronous extra-hepatic localizations of colorectal cancer. Surgical indications (in French). Presse Med 1993;22:515–20.
  14. Jarnagin WR, Bach A, Winston CB, et al. What is the yield of intraoperative ultrasonography during partial hepatectomy for malignant disease?. J Am Coll Surg 2001;192:577–83.[CrossRef][Medline]
  15. Gibbs JF, Weber TK, Rodrigez-Bigas MA, Driscoll D, Petrelli NJ. Intraoperative determinants of unresectability for patients with colorectal hepatic metastases. Cancer 1998;82: 1244–9.[Medline]
  16. Lefor AT, Hughes KS, Shiloni E, et al. Intra-abdominal extrahepatic disease in patients with colorectal hepatic metastases. Dis Colon Rectum 1988;31:100–3.[CrossRef][Medline]
  17. John TG, Greig JD, Crosbie JL, Miles WF, Garden OJ. Superior staging of liver tumors with laparoscopic ultrasound. Ann Surg 1994;220:711–9.[Medline]
  18. Rahusen FD, Cuesta MA, Borgstein PJ, et al. Selection of patients for resection of colorectal metastases of the liver using diagnostic laparoscopy and laparoscopic ultrasonography. Ann Surg 1999;230:31–7.[CrossRef][Medline]
  19. Tsioulias GJ, Wood TF, Chung MH, Morton DL, Bilchick A. Diagnostic laparoscopy and laparoscopic ultrasonography optimize the staging and resectability of intraabdominal neoplasms. Surg Endosc 2001;15:1016–9.[CrossRef][Medline]
  20. Jarnagin WR, Conlon K, Bodnewiewicz J, et al. A clinical scoring system predicts the yield of diagnostic laparoscopy in patients with potentially resectable hepatic colorectal metastases. Cancer 2001;91:1121–8.[CrossRef][Medline]
  21. Fong Y, Saldinger PF, Akhurst T, et al. Utility of 18F-FDG positron emission tomography scanning on selection of patients for resection of hepatic colorectal metastases. Am J Surg 1999;178:282–7.[CrossRef][Medline]
  22. Johnson K, Bakhsh A, Young D, Martin E, Arnold M. Correlating computed tomography and positron emission tomography scan with operative findings in metastatic colorectal cancer. Dis Colon Rectum 2001;44:354–7.[CrossRef][Medline]



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