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      Effect of preoperative chemotherapy on postoperative liver regeneration following hepatic resection as estimated by liver volume

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          Abstract

          Background

          In order to analyze postoperative liver regeneration following hepatic resection after chemotherapy, we retrospectively investigated the differences in liver regeneration by comparing changes of residual liver volume in three groups: a living liver donor group and two groups of patients with colorectal liver metastases who did and did not undergo preoperative chemotherapy.

          Methods

          This study included 32 patients who had at least segmental anatomical hepatic resection. Residual liver volume, early postoperative liver volume, and late postoperative liver volume were calculated to study the changes over time. From the histopathological analysis of chemotherapy-induced liver disorders, the effect on liver regeneration according to the histopathology of noncancerous liver tissue was also compared between the two colorectal cancer groups using Kleiner’s score for steatohepatitis grading {Hepatology, 41(6):1313–1321, 2005} and sinusoidal obstruction syndrome (SOS) grading for sinusoidal obstructions {Ann Oncol, 15(3):460–466, 2004}.

          Results

          Assuming a preoperative liver volume of 100%, mean late postoperative liver volumes in the three groups (the living liver donor group and the colorectal cancer groups with or without chemotherapy) were 91.1%, 80.8%, and 81.3%, respectively, with about the same rate of liver regeneration among the three groups. Histopathological analysis revealed no correlation between either the Kleiner’s scores or the SOS grading and liver regeneration.

          Conclusions

          As estimated by liver volume, the level of liver regeneration was the same in normal livers, tumor-bearing livers, and post-chemotherapy tumor-bearing livers. Liver regeneration was not adversely affected by the extent to which steatosis or sinusoidal dilatation was induced in noncancerous tissue by chemotherapy in patients scheduled for surgery.

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          Most cited references18

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          Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.

          To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Seventy-five percent of procedures were major hepatectomies (> or =3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, > or =3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.
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            Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates.

            Long-term survival is reported in patients with liver metastases of colorectal cancer. Recently, an increased number of reports on liver resection following neoadjuvant chemotherapy in patients with initially unresectable liver metastases has been published. We analysed all published or presented trials and retrospective studies that report the rate of objective response and the rate of resection of initially unresectable metastases to correlate objective response and the rate of resection of metastases. In studies that enrolled patients with metastases confined to the liver, 24-54% of patients were resected following chemotherapy, compared to 1-26% of patients in trials that included non-selected patients with metastatic colorectal cancer. A strong correlation was found between response rates and the resection rate in studies with patients with isolated liver metastases (r = 0.96, P=0.002). Likewise, in studies with non-selected patients, the resection rate of metastases also was associated with the objective response rate (r = 0.74, P <0.001). Patient selection and efficacy of pre-operative chemotherapy are both strong predictors for resectability of liver metastases. Resectability is a novel endpoint focusing on the curative potential of treatment compared with classical endpoints of response or progression-free survival that are important if palliation is the aim. Therefore, patients with potentially resectable liver metastases should be investigated in special trials and interdisciplinary teams.
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              Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors.

              The respective volumes of hepatic tumors and nontumorous parenchyma of 50 patients requiring hepatectomy of more than one segment of Healey for tumor removal were measured using computed tomography (Vol-CT). The volume estimated by Vol-CT was found to correlate with the real weight resected (P < .0001) with a mean absolute error of 64.9 mL. The ratio of the nontumorous parenchymal volume of the resected liver to that of the whole liver (R2) in 15 patients who underwent right or extended right hepatic lobectomy was 43% +/- 15%. Eight of 15 patients with R2s < 60% underwent the procedures without right portal vein embolization (PE). The other seven with R2s exceeding 60% or an indocyanine green retention rate after 15 minutes (ICG15) of 10% to 20% underwent PE: in six of seven, the nontumorous parenchyma of the right hepatic lobe became atrophic and in all seven, the volume of the remaining left hepatic lobe increased with a decrease in the mean R2 from 62% +/- 14% to 55% +/- 8% (P = .0006). In the remaining 35 who underwent other hepatectomy procedures, R2s also remained <60%. Overall, at surgery, in 27 with normal liver function (ICG15 < 10%), R2s exceeded 60% in one, remained at 50% to 60% in five, and <50% in 21, whereas 23 patients except for one with an ICG15 exceeding 10%, had R2s of <50%. The postoperative serum total bilirubin levels in 84% of the patients remained within the normal range and there was no surgery-related mortality. In conclusion, 1) Vol-CT can accurately assess the extent of liver resection, 2) individuals with normal liver function can undergo resection of up to 60% of the nontumorous parenchyma without the need for PE, and 3) PE can be used to reduce the size of the resected tissue and increase the volume of the remnant liver to approximate the target limits in individuals with large tumors or minimally abnormal liver function.
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                Author and article information

                Contributors
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central
                1477-7819
                2013
                13 March 2013
                : 11
                : 65
                Affiliations
                [1 ]Department of Surgery, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505, Japan
                Article
                1477-7819-11-65
                10.1186/1477-7819-11-65
                3621216
                23497123
                87ca22b4-d164-4aff-a670-d1667ebf8bb7
                Copyright ©2013 Takeda et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 May 2012
                : 15 February 2013
                Categories
                Research

                Surgery
                Surgery

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