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Clinical scenarios associated with localrecurrence after laparoscopicradiofrequency thermal ablationof colorectal liver metastasesErol Aksoy, MD, Shamil Aliyev, MD, Halit Eren Taskin, MD, Onur Birsen, MD, Jamie Mitchell, MD,Allan Siperstein, MD, and Eren Berber, MD, Cleveland, OH

Background. Over the last decade, radiofrequency thermal ablation (RFA) has been incorporated into thetreatment algorithm of patients with unresectable colorectal liver metastases (CLM). For this population,the local recurrence (LR) rate is a key parameter used to assess the success of RFA. LR is defined asdevelopment of new tumor abutting and/or in 1 cm of an ablation zone. The aim of this study is tocorrelate LR with other hepatic or extrahepatic recurrence and patient survival.Methods. Between 2000 and 2011, 252 patients with CLM underwent laparoscopic RFA of 883lesions. These patients were followed under a prospective protocol with quarterly liver computedtomography and blood work, including carcinoembryonic antigen levels quarterly for the first 2 years andthen biannually. Clinical scenarios associated with LR were identified and categorized as being ‘‘isolatedLR,’’ ‘‘LR associated with new liver disease,’’ or ‘‘LR associated with systemic disease.’’ Demographic,clinical, and survival data were assessed using analysis of variance, Chi-square test, and univariateand multivariate Kaplan–Meier analysis.Results. One hundred eighteen patients (47%) developed LR after their initial laparoscopic RFA. Thesewere 85 men (72%) and 33 women (28%), with a mean age of 70 ± 8 years. For this cohort, the meanof number of lesions was 3.1 ± 0.2 cm (range, 1–11) and dominant tumor size 2.9 ± 0.1 cm (range,0.7–6.5) at the time of initial RFA. The LR rate per lesion was 29%. Of the patients who developedtreatment failure at the RFA site, this was an isolated LR in 31 (26%) patients, associated with newliver disease in 51 (43%) and systemic metastases in 36 patients (31%). When patients with differentclinical scenarios associated with LR were compared, no clinical predictors were identified to differentiatethese subgroups. At a median follow up of 30 months (range, 3–113), the Kaplan-Meier median overallsurvival (OS) for patients with and without LR were 28 vs 31 months, respectively (P = .103). The OSfor patients whose LR was isolated, associated with new liver and systemic recurrences was 39, 26, and22 months, respectively (P = .009).Conclusion. This study shows that, although the presence of LR does not negatively impact on survival,the pattern of recurrent disease does. LR after RFA for CLM is most often associated with new liver andsystemic recurrences, reflecting the aggressive biology of cancer in patients channeled to this treatmentmodality. (Surgery 2013;154:748-54.)

From the Department of General Surgery, Cleveland Clinic, Cleveland, OH

OVER THE LAST DECADE, radiofrequency thermal abla-tion (RFA) has been incorporated into the treat-ment algorithm of patients with unresectablecolorectal liver metastases (CLM).1-3 For this

d at the Central Surgical Association annual meeting,4–16, 2013, Amelia Island, FL.

d for publication May 10, 2013.

requests: Eren Berber, MD, 9500 Euclid Avenue/F20,d, OH 44195. E-mail: berbere@ccf.org.

60/$ - see front matter

Mosby, Inc. All rights reserved.

x.doi.org/10.1016/j.surg.2013.05.014

URGERY

population, the local recurrence (LR) rate is akey parameter used to assess the success of RFA.LR is defined as development of new tumor abut-ting and/or in 1 cm of an ablation zone.4 Accord-ing to the literature, the LR rate ranges between 2and 60% for CLM.5-14 Although there are abun-dant data on factors affecting LR on a lesion basis,the clinical patterns of LR have not been describedin detail.4 In our clinical practice, we haveobserved that the pattern of recurrence, ratherthan the presence of LR, affects the overall onco-logic outcomes of the patients. The aim of thisstudy was to define the clinical scenarios associated

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with LR with regard to new hepatic or extrahepaticrecurrence, analyze their effects on survival, andidentify preoperative predictors of each scenario.

MATERIALS AND METHODS

Between 2000 and 2011, 252 patients with CLMunderwent laparoscopic RFA of 883 lesions at theCleveland Clinic Department of General SurgeryLiver Tumor Ablation Program. The ablationequipment consisted of various AngiodynamicsInc (Queensbury, NY) and R.I.T.A. Medical Sys-tems, Inc (Fremont, CA) 2-, 5-, and 7-cm cathetersthat were used with 50–200W generators atdifferent time points in the study. We havedescribed the technique of laparoscopic RFA inprevious studies.15,16 The patients were followedunder a prospective protocol with quarterly livercomputed tomography (CT) and blood work,including carcinoembryonic antigen levels quar-terly for the first 2 years and then biannually. Clin-ical scenarios associated with LR were identifiedand categorized as being ‘‘isolated LR,’’ ‘‘LR associ-ated with new liver disease,’’ or ‘‘LR associated withsystemic disease.’’

Indications for RFA were technical factors, pa-tient comorbidities, extrahepatic disease, and/orpatient decision. Each patient was triaged to RFA,resection, or other treatment options as a result ofmultimodality interaction and decision at theCleveland Clinic.

Demographic, clinical, and survival data wereassessed using analysis of variance, Chi-squaretesting, and univariate Kaplan–Meier analysis. Uni-variate Kaplan–Meier and multivariate Cox pro-portional hazards model were used to analyzefactors affecting LR. Ablation margin was calcu-lated by subtracting tumor size on preoperative CTfrom the size of ablation defect seen on 1 weekpost-ablation CT. Summaries of continuous vari-ables are represented in the form of mean values ±standard error.

RESULTS

After initial laparoscopic RFA, 118 patients(47%) out of 225 developed LR. These were 85men (72%) and 33 women (28%), with a mean ageof 70 ± 8 years. For this cohort, the mean ofnumber of lesions was 3.1 ± 0.2 (range, 1–11) anddominant tumor size 2.9 ± 0.1 cm (range, 0.7–6.5)at the time of initial RFA.

The LR rate per lesion was 29%. Factorsaffecting LR on univariate analysis were tumorsize, ablation margin, and proximity to bloodvessels. On the other hand, tumor segmentallocation, and central or peripheral location did

not affect LR. On multivariate analysis, tumor sizeand ablation margin were independent predictorsof LR (Table I; Figs 1–3). Tumors >5 cm had twicethe risk of LR compared with those <3 cm; tumorsablated with a <1-cm margin had a 1.9-foldincreased risk of LR compared with tumors witha >2-cm ablation margin.

Of the patients who developed treatment failureat the RFA site, this was an isolated LR in 31patients (26%), associated with new liver recur-rence in 51 (43%) and systemic metastases in 36patients (31%). When patients with differentclinical scenarios associated with LR werecompared, no clinical predictors to differentiatethese subgroups were identified (Table II).

At a median follow up of 30 months (range, 3–113), theKaplan–Meiermedianoverall survival (OS)for patients with (n = 118) and without (n = 107) LRwere 28 and 31 months, respectively (P = .103). TheOS for patients whose LR was isolated, associatedwith new liver and systemic recurrences was 39, 26,and 22 months, respectively (P = .009; Fig 4). The3-year OS for the same groups was 54%, 29%, and20%, respectively.

DISCUSSION

Treatment failure at the ablation site, known asLR, is a major weakness of RFA. Multiple studieshave looked at the incidence of this LR for CLM.5-14

Nevertheless, the clinical relevance and impact onsurvival have not been reported in detail. The objec-tive of this report was to focus on the clinical andoncologic consequences of LR from a contempo-rary Western experience. Our results show that,although the presence of LR did not negativelyimpact survival, the pattern of recurrent diseasedid. This was not surprising, because isolated recur-rences are amenable to repeat RFA or resection,with ultimate control of the index lesion in mostcases. However, LR after RFA for CLM was mostoften associated with new liver and systemic recur-rences, reflecting the aggressive biology of cancerin patients channeled to this treatment modality atour center, and these types of recurrences negativelyimpacted survival to a greater degree comparedwithisolated treatment failures.

In our previous study, we evaluated 335 patientswith 1,032 unresectable malignant liver tumorswho underwent laparoscopic RFA and analyzedthe incidence of LR.4 LR was identified 22% oftumors on CTwith a mean follow-up of 17 months.This was contiguous in 70% and adjacent in 30%.LR rate per tumor was greatest for CLM (34%).By univariate analysis, tumor type and size, abla-tion margin, liver segmental location, blood vessel

Table I. Multivariate Cox proportional hazardmodel for developing local recurrence

VariableHazard ratio(95% CI)

Pvalue

Dominant tumor size >5 vs <3 cm 2.0 (1.2–3.2) .011Dominant tumor size 3–5 vs <3 cm 1.6 (1.1–2.3) .018Dominant tumor size >5 vs 3–5 cm 1.2 (0.8–1.9) .376Ablation margin <1 vs >2 cm 1.9 (1.2–2.9) .006Ablation margin 1–2 vs >2 cm 1.3 (0.8–1.8) .263Blood vessel proximity near versus

away1.2 (0.8–1.7) .467

Fig 1. Local tumor control over time based on tumorsize.

Fig 2. Kaplan–Meier curves showing local tumor controlbased on the size of the ablation margin (size of ablationzone at 1-week computed tomographic scan minus thesize of liver tumor at pre-ablation scan).

Fig 3. Kaplan–Meier curves showing local tumor controlfor tumors near large-size liver vasculature versus thoseaway from such vessels.

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proximity, and type of ablation (first time versusrepeat) were found to affect LR. The Cox propor-tional hazard model identified tumor type, tumorsize, ablation margin, and blood vessel proximityto be independent predictors of LR. On the other

hand, we focused on CLM in the current study andidentified LR in 29% of lesions and 47% of pa-tients. The tumor-related factors affecting LRwere similar, except that proximity to blood vesselswas not an independent predictor of LR. Tumorsize and ablation margin were significant predic-tors of LR, on the other hand. The literature isnot clear about the influence of the proximity tolarge vessels on the risk of LR.17-19 Three compar-ative studies have found an increased risk,20-22

whereas 2 other studies did not.23,24 It is possiblethat the decrease of intrahepatic blood flow withlaparoscopy may mitigate the ‘‘heat sink effect’’during ablation.

Mulier et al14 reviewed the literature for LR afterRFA by analyzing 95 studies including 5,224 treatedliver tumors. LR rate varied widely between 2% and60%. In a univariate analysis, tumor-dependent fac-tors with significantly less LRs were smaller size,neuroendocrine metastases, nonsubcapsular loca-tion, and location away from large vessels.Physician-dependent favorable factors were opera-tive (open or laparoscopic) approach, vascularocclusion, general anesthesia, a 1-cm intentionalmargin, and a greater physician experience. In amultivariate analysis, significantly less LRs wereobserved for small size (P < .001) and an operative(versus percutaneous) approach (P<.001). The au-thors concluded that RFA by laparoscopy or laparot-omy resulted in superior local control, independentof tumor size. There was a suggestion to reserve thepercutaneous route mainly for patients who cannottolerate laparoscopy or laparotomy.

Percutaneous RFA has been reported to beassociated with higher LR rates compared withopen or laparoscopic RFA. Furthermore, it isinferior to open or laparoscopic RFA in terms of

Table II. Demographic and clinical parameters

Parameters Isolated (n = 31) New liver (n = 51) Systemic (n = 36) P value

Age (y) 62 ± 15 80 ± 12 63 ± 13 .539Gender (male/female) 21/10 38/13 27/9 .759ASA status 3.0 ± 0.1 2.8 ± 0.1 2.8 ± 0.1 .233Primary (colon/rectum) 25/6 35/16 24/12 .373Tumor size, cm (range) 2.8 ± 0.3 (0.7–6) 3.0 ± 0.2 (0.8–6.5) 3.1 ± 0.0 (1–6.5) .612Number of tumors (range) 3.1 ± 0.4 (1–11) 3.9 ± 0.3 (1–11) 3.3 ± 0.4 (1–10) .211CEA levels (ng/dL) 50 ± 28 119 ± 22 86 ± 25 .129Neoadjuvant chemotherapy 26 (84%) 50 (98%) 32 (89%) .126Adjuvant chemotherapy 27 (87%) 49 (96%) 35 (97%) .195Time to local recurrence (mos) 13 ± 2 7 ± 2 10 ± 2 .054

Continuous data are expressed as mean values ± standard error of the mean.ASA, American Society of Anesthesiologists; CEA, carcinoembryonic antigen.

Fig 4. Kaplan–Meier overall survival of different localrecurrence scenarios.

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tumor staging, because the abdominal cavity is notexplored.25,26 Last, laparoscopic ultrasonographyalso enables the identification of additional livertumors, not seen on preoperative imaging, in20% of the patients who are taken to the operatingroom for a liver RFA.27

In another large study, Van Duijnhoven et al13

reported on a total of 199 lesions in 87 patientswith CLM treated with RFA. The local failure ratewas 47%, and the average time to local disease pro-gression was 6.5 months. Factors that significantlycorrelated with increased failure rates were meta-chronous occurrence of liver metastases, largemean lesion size, and central tumor location.These authors underscored the importance of ac-curate electrode placement in achieving adequatetumor necrosis.

The utility of RFA in resectable patients is verycontroversial.28,29 There are also many questions ofdebate about the use of RFA for CLM in general.These are related to the indications, relatively

high rate of local treatment failure at the site ofablation, and most appropriate patient populationbased on tumor size and number. These need tobe kept in mind when selecting patients for RFA,especially in the era of laparoscopic liver resection.Nevertheless, in a mostly unresectable patient pop-ulation, our results show that LR is accompaniedby new liver disease in 47% and new extrahepaticdisease in 31% of the time, underscoring aggres-sive tumor biology in these patients. Therefore,we suggest the incorporation of these clinical sce-narios into the evaluation and counseling ofpatients, instead of discussing the crude LR rate af-ter RFA.

REFERENCES

1. Berber E, Rogers S, Siperstein A. Predictors of survival afterlaparoscopic radiofrequency thermal ablation of hepatocel-lular cancer: a prospective study. Surg Endosc 2005;19:710-4.

2. Machi J, Oishi AJ, Sumida K, et al. Long-term outcome ofradiofrequency ablation for unresectable liver metastasesfrom colorectal cancer: evaluation of prognostic factorsand effectiveness in first- and second-line management.Cancer J 2006;12:318-26.

3. Siperstein AE, Berber E, Ballem N, Parikh RT. Survival afterradiofrequency ablation of colorectal liver metastases:10-year experience. Ann Surg 2007;246:559-65.

4. Berber E, Siperstein A. Local recurrence after laparoscopicradiofrequency ablation of liver tumors: an analysis of 1032tumors. Ann Surg Oncol 2008;15:2757-64.

5. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation ofunresectable primary and metastatic hepatic malignancies:results in 123 patients. Ann Surg 1999;230:1-8.

6. Pawlik TM, Izzo F, Cohen DS, et al. Combined resection andradiofrequency ablation for advanced hepatic malignancies:results in 172 patients. Ann Surg Oncol 2003;10:1059-69.

7. Kuvshinoff BW, Ota DM. Radiofrequency ablation of livertumors: influence of technique and tumor size. Surgery2002;132:605-11.

8. Aloia TA, Vauthey JN, Loyer EM, et al. Solitary colorectalliver metastasis: resection determines outcome. Arch Surg2006;141:460-6.

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9. Curley SA, Izzo F, Abdalla E, et al. Surgical treatment ofcolorectal cancer metastasis. Cancer Metastasis Rev 2004;23:165-82.

10. Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and out-comes following hepatic resection, radiofrequency ablation,and combined resection/ablation for colorectal liver metas-tases. Ann Surg 2004;239:818-25.

11. Wood TF, Rose DM, Chung M, et al. Radiofrequency abla-tion of 231 unresectable hepatic tumors: indications, limita-tions, and complications. Ann Surg Oncol 2000;7:593-600.

12. Bilchik AJ, Wood TF, Allegra DP. Radiofrequency ablationof unresectable hepatic malignancies: lessons learned.Oncologist 2001;6:24-33.

13. van Duijnhoven FH, Jansen MC, Junggeburt JM, et al. Fac-tors influencing the local failure rate of radiofrequencyablation of colorectal liver metastases. Ann Surg Oncol2006;13:651-8.

14. Mulier S, Ni Y, Jamart J, et al. Local recurrence after hepaticradiofrequency coagulation: multivariate meta-analysis andreview of contributing factors. Ann Surg 2005;242:158-71.

15. Berber E, Tsinberg M, Tellioglu G, Simpfendorfer CH, Si-perstein AE. Resection versus laparoscopic radiofrequencythermal ablation of solitary colorectal liver metastasis.J Gastrointest Surg 2008;12:1967-72.

16. Tsinberg M, Tellioglu G, Simpfendorfer CH, et al. Compar-ison of laparoscopic versus open liver tumor resection: acase-controlled study. Surg Endosc 2009;23:847-53.

17. Elias D, Goharin A, El Otmany A, et al. Usefulness of intra-operative radiofrequency thermoablation of liver tumoursassociated or not with hepatectomy. Eur J Surg Oncol2000;26:763-9.

18. Francica G, Marone G. Ultrasound guided percutaneoustreatment of hepatocellular carcinoma by radiofrequencyhyperthermia with a ‘cooled tip needle’: a preliminary clin-ical experience. Eur J Ultrasound 1999;9:145-53.

19. Giovannini M, Moutardier V, Danisi C, et al. Treatment ofhepatocellular carcinoma using percutaneous radiofre-quency thermoablation: results and outcomes in 56patients. J Gastrointest Surg 2003;7:791-816.

20. Lu DS, Raman SS, Limanond P, et al. Influence of largeperitumoral vessels on outcome of radiofrequency ablationof liver tumors. J Vasc Interv Radiol 2003;14:1267-74.

21. Bowles BJ, Machi J, Limm WM, et al. Safety and efficacy ofradiofrequency thermal ablation in advanced liver tumors.Arch Surg 2001;136:864-9.

22. Machi J, Uchida S, Sumida K, et al. Ultrasound-guidedradiofrequency thermal ablation of liver tumors: percuta-neous, laparoscopic, and open surgical approaches.J Gastrointest Surg 2001;5:477-89.

23. Komorizono Y, Oketani M, Sako K, et al. Risk factors forlocal recurrence of small hepatocellular carcinoma tumorsafter a single session, single application of percutaneousradiofrequency ablation. Cancer 2003;97:1253-62.

24. Hori T, Nagata K, Hasuike S, et al. Risk factors for the localrecurrence of hepatocellular carcinoma after a single sessionof percutaneous radiofrequency ablation. J Gastroenterol2003;38:977-81.

25. White RR, Avital I, Sofocleous CT, et al. Rates and patternsof recurrence for percutaneous radiofrequency ablationand open wedge resection for solitary colorectal liver metas-tasis. J Gastrointest Surg 2007;11:256-63.

26. Park IJ, Kim HC, Yu CS, Kim PN, Won HJ, Kim JC. Radiofre-quency ablation for metachronous liver metastasis fromcolorectal cancer after curative surgery. Ann Surg Oncol2008;15:227-32.

27. Foroutani A, Garland AM, Berber E, et al. Laparoscopic ul-trasound vs triphasic computed tomography for detectingliver tumors. Arch Surg 2000;135:933-8.

28. Hammill CW, Billingsley KG, Cassera MA, Wolf RF, UjikiMB, Hansen PD. Outcome after laparoscopic radiofre-quency ablation of technically resectable colorectal livermetastases. Ann Surg Oncol 2011;18:1947-54.

29. Livraghi T, Solbiati L, Meloni F, Ierace T, Goldberg SN,Gazelle GS. Percutaneous radiofrequency ablation of livermetastases in potential candidates for resection: the ‘‘test-of-time approach.’’ Cancer 2003;97:3027-35.

DISCUSSION

Dr Naveed Ahmed (Jackson, MS): This is a very nicelydone and presented study. I know that your group, withDr Siperstein and yourself, have a huge experience inRFA, especially for colorectal metastases and other liversecondary tumors.

It was an interesting study that you have defined sortof a perioperative predictor, where you can assess failurerate or local failure rate of RFA. And I think thatinformation will help us to talk to our patients, to bewell-informed, and to have a more productive discussionwith them.

My question would be, sort of to bring you to the darkside, do you think laparoscopy has any advantage overpercutaneous RFA, and if that is true, why?

Dr Eren Berber (Cleveland, OH): This questioncomes frequently about why we are doing this laparos-copically versus percutaneously. The laparoscopicapproach provides a certain advantage compared withthe percutaneous approach, including the ability tostage the whole abdomen and also do more precise tar-geting. Actually, recent materials have also shown thatsurgically performed RFA, either laparoscopic or open,has a better success rate compared with percutaneous,and as well as fewer complications.

Dr Robert Martin (Louisville, KY): Two questions.One, you and I both know, we’ve talked about really opti-mizing the definition of what truly is a local recurrence.And I got a sense you had a 1-week scan and then youhad an 8-month scan. Can you help the audience ormaybe even me? I would say that that 3-month scan isyour true definition of whether you have ablation suc-cess. And then if you have recurrence after that, whenyou have an ablation success, then that would be a localrecurrence. If you could just clarify that because I wasn’table to get through that.

The second was, of your 3 groups, the isolatedrecurrence is probably no big deal. We can salvagethose. It’s the 51 that had liver-only recurrence. Canyou break that out to us as to which ones of those hadipsilateral, same lobe as the RFA, and thus maybe themore aggressive hepatobiliary surgeon would say thatyou should have resected that at first, versus the oneswho had contralateral lobe recurrence. Clearly, there,that’s a more aggressive biology, and maybe would neverbe a candidate for operative resection.

Dr Eren Berber: Wedefined local recurrence as any tu-mor growth arising from the ablated tumor, and also, to be

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fair and objective, any tumor within 1 cm of the ablatedfocus. We previously looked at this and showed that, atthe 1-week CT scan, you can actually tell whether there’sresidual tumor or not. But the subsequent CTscans reallydefined this when we found out that most of the local re-currences are evident within the first year. So we scanthe patients every 3 months. They all develop at differenttime points, different tumor aggressiveness.

Regarding your second question, I can’t give you thedata for this cohort because most of these were unresect-able. But recently---we have a paper that’s being reviewedby Surgery that should probably be in publication soon---Ithink the most relevant clinical group, where we lookedat patients with single tumors <3 cm, and we looked tosee how many at RFA, how many at resection. It endedup that despite our efforts, the groups were still not com-parable because RFA patients were still sicker and hadmore technically difficult tumors.

But in that patient population, when we look at localtumor recurrence, we looked at ipsilateral local recur-rence, and we did not find a difference between the RFAand the resection group regarding the ipsilateral tumor,I would say ipsilateral lobar disease-free survival.

Dr Margo Shoup (Warrenville, IL): Colorectal canceris a systemic disease. And all these patients are beingtreated now with systemic chemo or targeted therapyas well. And they’re all treated in a multidisciplinaryfashion. So I’m curious, you didn’t really talk aboutthis in your paper, how you work with your medicaloncology colleagues to treat these patients. Are they get-ting chemotherapy before RFA, after RFA? What is yourprotocol that you use, and have you noticed a differencein the timing of the chemo with the recurrence of thetumor in the liver or recurrence systemically?

Dr Eren Berber: Because we interact with a lot ofoncology institutions as well as regional, the chemo-therapy practice patterns were not standard. But, in gen-eral, patients presenting with multiple metastases, theygenerally undergo a course of chemotherapy. Most ofthe time, 6 cycles. And if they have persistent disease,then they are referred to us. And then we counsel the pa-tients for either resection or ablation. And then theycontinue with chemotherapy postoperatively.

The exclusions are patients presenting with maybesolitary lesions. Sometimes we have proceeded with aresection or ablation before chemotherapy, but these arein the minority of the patients. And in this cohort, about90% of the patients are exposed to preoperative andpostoperative chemotherapy of various regimens.

Dr Thomas Stellato (Cleveland, OH): Can you tellme, was there any benefit provided by a prolonged dura-tion between the primary and recurrence in the liver?And did you do any of these ablations synchronouswith resecting of your primary?

Dr Eren Berber: I think, in 10patients, we did concom-itant RFA and resection. And the survival of those patientswere in between those 2 curves that I showed you.

Also, as I mentioned, we used RFA and resectioncomplementary. So overall, in a cohort of 400 patients,

about 50patients endedupundergoingboth treatments atdifferent timepoints for recurrence fromeither approach.And then, their survival was, again, somewhere in betweenthe RFA and the resection curve that I showed you.

Regarding the interval between the diagnosis ofprimary and metastases, we have not found that, in ourprevious studies, to affect survival. Likewise, a synchro-nous versus metachronous presentation was not foundto affect survival in our previous studies.

Dr William D. Turnipseed (Madison, WI): This isn’tan area of my expertise, but, at our institution, one ofour former faculty members did extensive research inthis area. I have 2 technical questions.

First, have you been able to correlate success andfailure of ablation rates with anatomic location of thelesions within the liver? Because heat dissipation nearvascular structures really compromises the effect and theefficiency of heat therapy.

And second, have you explored cryotherapy asopposed to thermal ablation? And do they correlate, inyour experience, if you have any experience in that area?

Dr Eren Berber: We have looked at that in our previ-ous studies, and anatomic location actually did not affectthe success rate. As I showed you, what affected the suc-cess rate was the tumor size and your ablation margin.Analogous to resection, we tried to get at least a 1-cmmargin in these tumors. And we see that the tumorsthat are ablated with a larger margin have less chanceof recurrence.

In our earlier studies, we got a hint that the tumorslocated to the major blood vessels, these are bloodvessels >4 mm, had a greater chance of recurrence. Butas our data accumulated, we have not seen it in ourrecent papers, including this study.

And I ascribe that to maybe our experience. Also, weall know that, with laparoscopy, the liver blood flowdecreases about 20–30%. Maybe analogous to Pringle,that maybe mitigates that effect.

Regarding cryotherapy, we haven’t had experiencewith that. But the literature shows that cryotherapyversus ablation has a higher local recurrence rate aswell as complications. So, across the country, RFA ispreferred over cryoablation now.

Dr Richard A. Prinz (Evanston, IL): Dr Berber, I apol-ogize. Everyone in the room knows I have minimal tolimited experience or knowledge in this area, but if avascular surgeon can ask questions, I feel I also should.I’m sorry if it’s a very naive question.

The CT examples you showed---and, obviously, theywere just 1 cut---but those looked like eminently resect-able lesions. So this is being done laparoscopically now.And I could contemplate that patients who might behesitant to undergo an open large resection might bewilling to have a laparoscopic resection. Could you putthis into context for me?

Dr Eren Berber: Dr Prinz, your comments are alwaysvaluable for us. First , obviously, as you mentioned, Ididn’t show all the cuts. So these patients had more dis-ease in the remaining cuts, or the patients who did not

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have additional lesions, they were preempted. Like, wesee patients who are 80 years old, they have a pacemaker,ejection fraction of 20%, and they have a single lesion.Always, those patients are not candidates for a resection.

Also, our practice patterns have also changed over thelast 5 years, in that we have incorporated laparoscopicresection significantly in the treatment of these patients.And I have to admit that most of these patients whounderwent ablation are now undergoing laparoscopicresection, but these are more recent data.

Dr Syed Ahmad (Cincinnati, OH): I want to go backto the question that Dr Shoup asked. You’ve demon-strated that a significant number of people had recur-rence at a distant site and/or local site, and those arepeople who most likely did not benefit from the proce-dure you performed. So with such a high recurrencerate, why not give all these people neoadjuvant therapyto select out the biology of the tumor, and a subset of pa-tients are more likely to benefit from a local procedure,like RFA.

And if you have local recurrence within that lobe, asRob pointed out, then you can do a lobectomy. If youhave a contralateral recurrence, you’re not going to doany surgery. So why do RFA as the first option? Why notgive these people chemotherapy to select out thebiology, and then determine your operation based onthat?

Dr Eren Berber: Because of time limitations, I apolo-gize, we didn’t make it clear. But we state in the paperthat 90% of these patients had actually neoadjuvantchemotherapy. Actually, when a patient is referred tous from oncology with, let’s say, 6 or 7 tumors, wedon’t perform ablation. We send them back to the oncol-ogist to give chemotherapy and observe them for 3–6months to make sure that they don’t blossom with dis-ease before we treat them.

So these patients actually go through the conven-tional practice patterns in surgical and medicaloncology, and then are channeled to RFA if they don’thave a response and they are not resectable.