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Unresectable Colorectal CA
Unresectable Colorectal CA
failure, respiratory insufficiency, severe coronary artery disease, or nation (carcinoembryonic antigen and CA 19.9) during the first 2
failure of other organs likely to contraindicate treatment were not years, then every 6 months thereafter.
included.
Data were collected prospectively for patients who underwent Statistical Evaluation
surgery and retrospectively for patients treated with chemotherapy The statistical analysis was performed using the 2 test for
alone. quantitative values and the Student t test for qualitative values. A P
value of less than 0.05 was considered statistically significant.
Survival was determined using the Kaplan-Meier method. Overall
HAI Protocol
survival was calculated from the date of the diagnosis of CRCLM
Patients with unresectable CRCLM, without extrahepatic dis- for all patients. In addition, overall survival and progression-free
ease, received HAI of oxaliplatin after failure of a first-line of survival were calculated from resection of CRCLM, for operated
systemic chemotherapy, or as first-line therapy during prospective patients. All statistical calculations were performed using StatView
studies. A catheter connected to a subcutaneous chamber (Celsite software.
T202F, 6,5F, B Braun) was installed either during open surgery or
interventional radiology to exclusively perfuse the hepatic artery and
liver parenchyma. Any additional left hepatic artery originating from
RESULTS
the left gastric artery or right hepatic artery originating from the Patient Characteristics
superior mesenteric artery was ligated or embolized. Isolated liver A total of 87 patients with unresectable isolated CRCLM
perfusion was first verified with fluorescein during surgery or were included in the final analysis. Of total, 60 patients were treated
standard angiography during interventional radiology. An isotope between May 1999 and December 2003, and 27 between January
perfusion study was also performed before each chemotherapy 2004 and May 2007. Their demographic characteristics and clinical
infusion. The chemotherapy protocol consisted of an initial HAI features are described in Table 1.
bolus of 100 mg/m2 oxaliplatin, 200 mg/m2 intravenous (i.v.) The patients had advanced liver disease with synchronous
leucovorin, and 400 mg/m2 i.v. 5FU over a 2-hour period followed metastases in 74 (85%) and bilateral, centrohepatic, or unilateral
by an infusion of 2400 mg/m2 i.v. 5FU over a 2-day period lesions after a previous lobectomy for metastases in 78 patients
(modified LV5FU2 protocol). Chemotherapy was repeated every 2 (89%). The median number of lesions was 7 (1– 60) and the median
weeks, in our institution. Chemotherapy doses could be modified in size of the largest lesion was 50 mm (10 –150). Eighteen patients
the event of local or systemic toxicity. The HAI treatment was (20.6%) had previously been operated on for CRCLM. The main
stopped if major toxicity, serious technical catheter-related prob- reason for unresectability was an insufficient estimated FLR in 75
lems, or disease progression occurred. patients (86%). Other reasons for palliative treatment alone were
vascular invasion (6 patients), progression under chemotherapy (4
Surgical Techniques patients), and the appearance of unresectable extrahepatic metastasis
Chemotherapy was stopped at least 4 weeks prior to surgery. (2 patients).
Preoperative evaluation included thoracic and abdominal computed
tomography (CT) scans for all patients. Since 2003, contrast-en- Hepatic Arterial Infusion and Systemic
hanced ultrasound has also been performed in most cases. The Chemotherapy
positron emission tomography scan and MRI were added when All 87 patients were fitted with an intraarterial catheter
considered necessary. In addition, liver function was assessed in all connected to a subcutaneous chamber. The catheter was installed
patients by the indocyanin green clearance (ICG) test, as described during open surgery in 47 patients and during interventional radiol-
by Makuuchi et al.14 Patients were considered to have resectable ogy in the remaining 40 patients. This last technique has been used
disease when the tumor response allowed resection and/or radiofre- by our team since 2002 and is now preferred over open surgery if
quency (RF) ablation of all CRCLM seen on imaging (R0 resection), patients do not require surgery for another reason.
with a sufficient FLR. Hepatic resections were performed by 2 About 79% of patients had received prior treatment with
senior surgeons. Bleeding was controlled using intermittent pedicle either systemic oxaliplatin or irinotecan, thus explaining the long
clamping and low central venous pressure. Parenchyma dissection
was carried out using the Kelly crush and bipolar dissection. Radio-
frequency ablation was preferred over extensive anatomic resection
TABLE 1. Demographic Characteristics and Clinical
for small centrally located lesions (⬍2.5 cm), to preserve hepatic
Features of 87 Patients
parenchyma in these heavily treated patients.15 Previously detect-
able liver metastases that were no longer visible after chemotherapy Characteristics Values
(or “missing metastases”) were resected if they could be precisely Sex
localized and if the estimated FLR was sufficient.15 A major hepa-
Male 44
tectomy was defined as resection of more than 3 hepatic segments.
Female 43
Age
Follow-Up
Median (range) yr 57 (32–77)
Patients on chemotherapy were followed up after each che-
motherapy course and tumor response was evaluated every 3 Primary tumor
months. Tumor response to chemotherapy was evaluated according Colon 62
to RECIST criteria16 by abdominal CT scan or, if not assessable on Rectum 23
CT scan, by liver MRI or contrast-enhanced ultrasound. Resectabil- 2 synchronous sites 2
ity was then reevaluated by a multidisciplinary team composed of CEA—median (range) mol 102 (1–44,130)
medical oncologists, surgeons, radiologists, and radiotherapists. Previous chemotherapy
Operated patients were followed up every 3 months and Chemonaive 19
screened for postoperative complications or tumor recurrence by Previous chemotherapy 68
clinical evaluation, abdominal CT scan, and tumor marker determi-
comes in our study are however clear and solid. It was conducted in rate of postoperative recurrences is still high. Chemotherapy
a single center, with the same multidisciplinary team evaluating intensification, notably with targeted therapy, is definitely a
patients from the beginning right through to the end. As the resect- strategy worth exploring.
ability status is to some extent subjective, this is an important point
to consider when conducting and evaluating studies on this issue. ACKNOWLEDGMENT
For example, in the study on hepatic resection after cetuximab The authors thank Lorna Saint Ange for editing.
rescue for CRCLM, Adam et al described that they included 133
patients from their own hospital and subsequently resected 6.7% of REFERENCES
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