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Objective: To investigate the clinical implications of BRAF -mutated (mut BRAF ) colorectal liver metastases (CRLMs)., Background: The clinical implications of mut BRAF status in CRLMs are largely unknown., Methods: Patients undergoing resection for mut BRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mut BRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management., Results: A total of 240 patients harboring BRAF -mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P =0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P <0.001) but not OS (33.5 vs 41 mo, P =0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P =0.01) and similar OS (30 vs 40 mo, P =0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P <0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P =0.004). All results continued to hold true in the multivariable OS analysis., Conclusions: Although surgery may be futile in patients with BRAF -mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: outcome of patients who develop resectable metachronous colorectal liver metastases (CLM) after adjuvant oxaliplatin-based chemotherapy for Stage III colorectal cancer (CRC) is not well defined and the value of preoperative chemotherapy is controversial., Methods: From 2006 to 2013, all patients undergoing liver resection for Class I metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC, across 32 French academic centers, were included., Results: Sixty-two patients with an average of 2 ± 1 CLM were included. Thirty-two (52%) patients received preoperative chemotherapy. There was no significant difference in the characteristics of CLM between patients with or without preoperative chemotherapy. After a median follow-up of 29 months, 3-year overall and disease-free survival rates were 79.8% and 34.6%, respectively. The median disease-free survival was not different in patients with or without preoperative chemotherapy (17 vs. 35 months respectively, p = 0.112). In multivariate analysis, only CEA level > 200 ng/ml was associated with the risk of recurrence (p = 0.027; OR = 4.7, 95% CI = 1.2-18.7)., Conclusion: Liver resection provides a good outcome in patients with limited metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC. The interest of preoperative chemotherapy is not obvious and should be tested in a prospective controlled study., (© 2022 Wiley Periodicals LLC.)

Background: BRAF V600E-mutant colorectal cancers (CRCs) are associated with shorter survival than BRAF wild-type tumors. Therapeutic decision-making for colorectal liver metastases (CRLM) harboring this mutation remains difficult due to the scarce literature. The aim was to study a large cohort of BRAF V600E-mutant CRLM patients in order to see if surgery extend overall survival among others prognostic factors., Methods: BRAF V600E-mutant CRCs diagnosed with liver-only metastases, resected or not, were retrospectively identified between April 2008 and December 2017, in 25 French centers. Clinical, molecular, pathological characteristics and treatment features were collected. Overall survival (OS) was defined as the time from CRLM diagnosis to death from any cause. Cox proportional hazard models were used for statistical analysis., Results: Among the 105 patients included, 79 (75%) received chemotherapy, 18 (17%) underwent upfront CRLM surgery, and 8 (8%) received exclusive best supportive care. CRLM surgery was performed in 49 (46.7%) patients. CRLM were mainly synchronous (90%) with bilobar presentation (61%). The median OS was 34 months (range, 28.9-67.3 months) for resected patients and 10.6 (6.7-12.5) months for unresected patients (P < 0.0001). In multivariate analysis, primary tumor surgery (hazard ratio (HR) = 0.349; 95% confidence interval (CI) 0.164-0.744, P = 0.0064) and CRLM resection (HR = 0.169; 95% CI 0.082-0.348, P < 0.0001) were associated with significantly better OS., Conclusions: In the era of systemic cytotoxic chemotherapies, liver surgery seems to extend OS in BRAF V600E-mutant CRCs with liver only metastases historical cohort., (© 2022. The Author(s).)

Background: To report the current clinical practice of French physicians for metachronous resectable liver metastasis (LM) occurring after a FOLFOX adjuvant chemotherapy for primary cancer., Methods: Twenty four clinical situations were proposed to a panel of experts via 4 learned societies. Clinical situations varied according time of recurrence (early between 6 and 12 month or > 12 month), extension of LM (limited ≤ 2 or extended > 2 lesions), presence of a neuropathy or not, and of a RAS or BRAF mutation., Results: A total of 157 physicians participated in this study. A consensus was reached in 17 (71%) clinical situations. For an early limited recurrence, whatever presence of neuropathy, the preferred therapeutic approach (45%) was upfront surgery. For an early extended recurrence, whatever presence of neuropathy, there was a consensus (64%) for a preoperative chemotherapy by FOLFIRI + biologic agent. For a late recurrence without neuropathy, there was a consensus (50%) for a preoperative FOLFOX chemotherapy, whatever the extension of LM. For a late recurrence with neuropathy, upfront surgery was chosen (52%) for limited LM, and preoperative chemotherapy by FOLFIRI + biologic agent (73%) for extended LM. No response was influenced by the RAS mutation status. There was a strong consensus for intensified preoperative chemotherapy in all clinical situations for BRAF-mutated LM., Conclusions: This national survey provides an overview of the practice patterns in the treatment of LM occurring after adjuvant FOLFOX for primary. It could be a basis to establish expert's recommendations for the clinical practice.

Background: The clinical significance of discordant radiological and pathological response to preoperative chemotherapy of colorectal liver metastases (CLM) is unknown., Methods: From 2011 to 2016, all eligible patients undergoing resection for CLM after preoperative chemotherapy were included at two centres. Patients were categorized according to radiologic response using RECIST as Rad-responders (complete/partial response) or Rad-non responders (stable disease) and according to Blazer et al. pathologic response grade as Path-responders (complete/major response) or Path-non responders (minor response). Survival outcome was analysed according to radiologic and pathologic response., Results: Among 413 patients undergoing resection of CLM, 119 fulfilled the inclusion criteria. Among these, 52 (44%) had discordant radiologic and pathologic response including 27 Rad-non responders/path responders and 25 Rad-responders/Path-non responders. Rad-non responders/path responders and Rad-responders/Path-non responders had similar characteristics except for the proportion receiving more than 6 cycles of preoperative chemotherapy (7/27 vs 16/25; P = 0.017). Median disease-free survival was not different in patients with or without discordant radiologic and pathologic responses (P = 0.195) but the type of discordance had an impact on oncologic outcome as median disease-free survival was 13.9 months (95% CI 5.7-22.2 months) in Rad-non responders/Path responders and 8.6 (6.2 - 10.9 months) in Rad-responders/Path-non responders (P = 0.034). Univariate and multivariate analysis showed that major pathologic response was associated with improved disease-free survival (OR 0.583, 95% CI 0.36-0.95, P = 0.031)., Conclusion: A discordant radiologic and pathologic response is common after preoperative chemotherapy for CLM. In these patients, pathologic response drives oncologic outcome.

Background: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs., Methods: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval., Results: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034)., Conclusion: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer., (© 2019 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Background: Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT®) can reduce postoperative morbidity in liver resection for cancer., Methods/design: Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT®) or control supplement (isocaloric isonitrogenous supplement--IMPACT CONTROL®) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis., Discussion: The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer., Trial Registration: Clinicaltrial.gov: NCT02041871.

Background: No standard treatment for advanced rectal cancer with synchronous resectable liver metastases (LM) has been defined. Radiochemotherapy prior to simultaneous or staged curative resection of both primary tumor and LM is one of the treatment options available. The response of LM to radiochemotherapy has never been evaluated and, in particular, the risk for progression of LM is unknown., Methods: Between 2000 and 2011, 20 patients underwent preoperative radiochemotherapy for advanced rectal cancer with synchronous limited but resectable LM. Imaging responses of LM to radiochemotherapy were analyzed on per-patient and per-lesion bases using Response Evaluation Criteria in Solid Tumors (RECIST) criteria., Results: Of the patients, 20 had 41 LM; 15 of the 20 patients (75%) had rectal cancer with expected circumferential margins <1 mm on magnetic resonance imaging (MRI), and 50% had a solitary LM before treatment. Of the patients, 13 received oxaliplatin-based chemotherapy, and 7 received fluorouracil (FU)-based chemotherapy in combination with radiation. Of the 41 LM, 7 showed complete response (17%); 7 showed partial response (17%); 20 remained stable (49%); and 7 progressed (17%). Of the 25 LM treated with oxaliplatin-based chemotherapy, only 1 LM (4%) progressed. All 20 patients were suitable for resection of LM with curative intent after the radiochemotherapy., Conclusion: In patients with advanced rectal cancer and synchronous limited, but resectable LM, the risk for progression of LM during radiochemotherapy is low, especially if the chemotherapy regimen contains oxaliplatin. This low risk does not compromise a curative surgical approach to LM., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM)., Methods: One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response-defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm)-was assessed by a central pathology reviewer and local pathologists., Results: Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P = .002, .009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P = .028, .043), number of CLM (P = .038, . 037), and margin (P = .011, .016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P = .004, .015), duration of preoperative chemotherapy (P = .025), number of nodules (P = .027), and margin (P = .014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ = .82) and substantial agreement (κ = .76) for tumor thickness between the central reviewer and local pathologists., Conclusions: Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM., (Copyright © 2013 American Cancer Society.)

Background: The significance of complete calcification of liver metastases on imaging is unknown. This study was conducted to determine whether complete calcification of liver metastases after chemotherapy, as assessed by imaging, was synonymous with sterilization of disease., Methods: Imaging by triphasic contrast-enhanced helical CT scan and abdominal ultrasound showed complete calcification of eight liver metastases in four patients after systemic chemotherapy. All eight completely calcified liver metastases were resected within four weeks of imaging. Histological and surgical findings were analyzed to see whether there was any correlation between radiological and pathological status for completely calcified liver metastases., Results: The pretreatment median diameter at initial imaging of the eight liver metastases that became completely calcified after chemotherapy was 24 mm. In all eight resected calcified liver metastases, pathological examination showed the presence of residual viable tumor cells. Most of the tumor volume was occupied by calcification, necrosis and fibrosis; but small discrete islands of viable tumor cells were detected at the periphery of lesions., Conclusions: This preliminary study shows that although imaging evidence of complete calcification of liver metastases may be a good indicator of chemotherapy response, it does not imply sterilization of the malignancy., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The majority of patients with colorectal liver metastases receive systemic chemotherapy. In the context of unresectable liver metastases, the objective of chemotherapy based on new and more effective regimens is not only to prolong survival, but also to induce enough response and shrinkage of the tumor to render resectable patients initially not deemed to be surgical candidates. In patients with resectable liver metastases, the goal of chemotherapy is to improve the outcome after surgery and especially to decrease the risk of recurrence. Although the principles of combined modality treatment become widely accepted, this therapeutic strategy is also associated with potential risks related to the preoperative use of chemotherapy.

Combining surgery and chemotherapy in the treatment of patients with colorectal hepatic metastases is increasingly becoming the standard of care. However, controversy remains regarding the juxtapositioning of chemotherapy and surgery, the duration of chemotherapy, and particularly, the use of preoperative chemotherapy in the treatment of patients with initially resectable metastases. The arguments for and against the different approaches presented are based on the data published in the medical literature and on the data presented at the most recent major oncology meetings, coupled with the personal experience of the authors. For patients with liver metastases that are resectable at presentation, perioperative chemotherapy has become the standard treatment in many institutions, with the recommendation that surgery is performed after a maximum of 6 cycles of systemic therapy. In the case of patients with initially unresectable liver metastases receiving preoperative systemic therapy, patients should be carefully monitored and surgery performed as soon as the metastases become resectable. All patients should, where possible, be treated by a multidisciplinary team. Going forward, it needs to be established whether more intensive treatment (ie, perioperative versus postoperative systemic therapy) is merited for the treatment of patients with initially resectable disease, and what the precise contribution of new therapeutic agents in these settings is, based on new prospective randomized trial data.

Surgical resection remains the only treatment of colorectal liver metastases that can ensure long-term survival and cure in some patients, but only a minority of patients with liver metastases is directly amenable to surgery. Cancer relapse is observed in the majority of patients after resection of liver metastases despite progress in surgical technique and improved surgical skills. In order to decrease the risk of cancer relapse, it has been proposed to combine surgery and chemotherapy, which could be administered before, after or before and after surgery. It has been demonstrated that perioperative chemotherapy can reduce the risk of cancer relapse and should be considered as the standard of care for most patients with resectable colorectal liver metastases. However perioperative chemotherapy has also potential disadvantages. This review will summarize the current data on the rationale, benefits and potential disadvantages of perioperative chemotherapy in patients with resectable colorectal liver metastases., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Background: Liver metastases develop in 40-50% of patients with colorectal cancer and represent the major cause of death in this disease. Surgical resection remains the only treatment procedure that can ensure long-term survival and provide cure when liver metastases can be totally resected with clear margins, when the primary cancer is controlled, and when there is no nonresectable extrahepatic disease. Five-year survival rate after surgical resection of colorectal metastases varies from 25% to 55%, but cancer relapse is observed in most patients., Aim: To review the potential benefits and disadvantages of neoadjuvant chemotherapy administered before surgery to patients with initially resectable metastases., Results: European Organization for Research and Treatment of Cancer (EORTC) study 40983 has shown that neoadjuvant chemotherapy could reduce the risk of relapse by one-quarter, and allows to test the chemosensitivity of the cancer, to help to determine the appropriateness of further treatments, and to observe progressive disease, which contraindicates immediate surgery. Neoadjuvant chemotherapy can induce damage to the remnant liver. Oxaliplatin-based combination regimen is associated with increased risk of vascular lesions, whereas irinotecan-containing regimens have been associated with increased risks of steatosis and steatohepatitis. Analysis of EORTC study 40983 showed that administration of six cycles of neoadjuvant systemic chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) was associated with moderate increase of the risk of reversible complications after surgery, but mortality rate was below 1% and not increased. If patients are not overtreated, chemotherapy before surgery is well tolerated. The integration of novel targeted agents in combination with cytotoxic drugs is a promising way to improve outcome in patients with advanced colorectal cancer. Preliminary trials have shown that targeted agents combined with cytotoxic regimens can increase tumor response rates. Another impact of preoperative chemotherapy is that metastases that respond to treatment may no longer be visible on computed tomography (CT) scan or at surgery. Patients should be carefully monitored and receive surgery before metastases disappear., Conclusion: Treatment of most patients with liver metastases-those with resectable metastases as well as those with initially unresectable metastases-should start with chemotherapy. If drugs are well chosen and the duration of treatment is monitored with care during multidisciplinary meetings, benefits largely outweigh potential disadvantages.

Background: The aim of this study was to determine the effect of chemotherapy on the accuracy of CT scan for the preoperative evaluation of colorectal liver metastases (LM)., Method: Between 1999 and 2005, 92 patients with less than six LM at diagnosis underwent surgery within four weeks of CT scan. Of these 92 patients, 60 had received chemotherapy before surgery (chemotherapy group), whereas 32 were operated without preoperative treatment (control group). Histological and surgical findings were compared with helical CT results., Results: On a per lesion basis, the sensitivity of CT scan for the detection of LM was 71% in the chemotherapy group and 76% in the control group. On a per patient basis, the sensitivity of CT scan was 54% in the chemotherapy group and 69% in the control group. Discrepancies between CT scan and surgical or histological findings, including both false-negative and false-positive lesions, were found in 32 patients from the chemotherapy group and 10 patients from the control group (p=0.0471). In multivariate analysis, chemotherapy (p=0.032), number of LM > 3 (p=0.034), and steatosis > 30% (p=0.012) were risk factors for inadequate staging of LM by CT scan., Conclusions: Chemotherapy reduces the accuracy of CT scan for preoperative evaluation of colorectal LM.

Background: Chemotherapy for colorectal liver metastases (CLM) may be associated with pathologic changes to the liver parenchyma, possibly increasing the risk of surgery. The aim of this study was to determine the risk factors for chemotherapy-associated liver injuries (CALI)., Methods: From 1998 to 2006, 146 patients underwent a liver resection for CLM within 3 months of preoperative chemotherapy. CALI were defined as follows: steatosis > or =30%, or steatohepatitis, or moderate or severe sinusoidal lesions. Univariate and multivariate analysis were used to examine the relationship between CALI and 36 other preoperative factors., Results: Pathologic examination showed CALI in 74/146 patients (51%), including sinusoidal lesions (n = 50), steatosis > or = 30% (n = 32), and steatohepatitis (n = 15). Twenty-three patients had overlapping CALI. In multivariate analysis, BMI > 27 (P = .002), hyperglycemia > 7 mmol/l (P = .006), and an interval between chemotherapy and surgery < 4 weeks (P = .011) were independent risk factors for CALI, whereas aspirin intake was associated with reduced risk of CALI (P = .002). In multivariate analysis, synchronous metastases (P = .015), unresectable liver metastases at diagnosis (P = .034), GGT plasma level > 1.5N (P = .028), and oxaliplatin-based chemotherapy (P < .01) were risk factors for sinusoidal lesions. Aspirin intake was associated with reduced risk for sinusoidal lesions (P = .03). In multivariate analysis, BMI > 27 (P = .026) was the only risk factor for steatosis or steatohepatitis., Conclusion: In patients with CLM, there are few preoperative risk factors for CALI. In patients treated by oxaliplatin-based chemotherapy, aspirin intake appears to be associated with a reduced risk of sinusoidal lesions and should be tested in a randomized phase II study.

A multidisciplinary approach is necessary to determine the optimal treatment for individual patients with liver metastases. The benefits of surgical resection and systemic chemotherapy are well established Surgical resection is the only treatment that can ensure long-term survival and cure in some cases. However, only a minority of patients with liver metastases are amenable to surgery and recurrences are still observed after resection in two-thirds of patients. Efforts are being made to increase the number of candidates for surgery and to reduce the risk of post-operative recurrence, notably by means of perioperative chemotherapy and new surgical techniques.

Surgical resection remains the only treatment of colorectal liver metastases that can ensure long-term survival and cure in some patient. However, only a minority of patients with liver metastases are amenable to surgery. Other patients can benefit from modern chemotherapy regimens, which achieve high response rates but are rarely sufficient for cure. In patients with unresectable metastases, neoadjuvant chemotherapy may increase the number of candidates for potentially curative resection, hence affording these patients the possibility of prolonged survival. For patients with resectable metastases, it is likely that the benefit of neoadjuvant chemotherapy before surgery will be demonstrated in the near future but is not yet validated. The integration of novel targeted agents will probably transform the therapeutic strategy for colorectal liver metastases.

Background: Prolonged systemic preoperative chemotherapy induces pathologic changes in liver parenchyma. The consequences of vascular occlusion on liver submitted to prolonged preoperative systemic chemotherapy are not known. The aim of this case-matched study was to assess which method of vascular occlusion is most appropriate for major liver resection in patients who have undergone prolonged preoperative systemic chemotherapy., Methods: Among 305 patients who had liver resection for colorectal metastases from 1998 to 2003, 28 underwent major liver resections under portal triad clamping after more than 6 cycles of preoperative chemotherapy (TC group). These 28 patients were compared with 32 patients matched for age, sex, ASA status, number of liver metastases, type of liver resection, and type of preoperative chemotherapy, but who had major liver resection under hepatic vascular exclusion after more than 6 cycles of preoperative chemotherapy (VE group)., Results: There was no postoperative mortality. The morbidity rate was 18% after TC and 43% after VE (P = 0.044). Pulmonary complication rate was greater after VE (31% vs 3%, P = 0.017). The transfusion rate was 50% in the TC group and 40% in the VE group (P = 0.482). Postoperative changes of liver function tests were comparable in the two groups except for the prothrombin time, which was more prolonged from day 1 (P = 0.003) to day 5 (P = 0.04) after VE., Conclusion: Vascular occlusion can be used with no mortality and acceptable morbidity for major liver resection after prolonged preoperative chemotherapy. TC should be preferred to VE, permitted by the location of the neoplasm.

Purpose: Most patients with colorectal liver metastases (LMs) receive systemic chemotherapy. This study aimed to determine the significance of a complete response on imaging of LMs after chemotherapy., Patients and Methods: Between 1998 and 2004, 586 patients were treated for colorectal LMs in one institution. Of these, 38 with the following criteria were included in the study: fewer than 10 LMs before chemotherapy; disappearance of one or several LMs on computed tomography (CT) scan and ultrasound; surgery with intraoperative ultrasound within 4 weeks of imaging; no extrahepatic disease; follow-up at least 1 year after surgery., Results: Overall, 66 LMs disappeared after chemotherapy as seen on CT scan. Persistent macroscopic disease was observed at surgery at the site of 20 of 66 LMs, despite CT scan showing a complete response. The sites of 15 initial LMs that were not visible at surgery were resected. Pathologic examination of these sites of LMs, considered in complete response, showed viable cancer cells present in 12 of 15 cases. The sites of 31 initial LMs that were not visible at surgery were left in place during surgery; after 1 year of follow-up, 23 of 31 LMs considered in complete response had recurred in situ. Overall, persistent macroscopic or microscopic residual disease or early recurrence in situ were observed in 55 (83%) of 66 LMs having a complete response on imaging., Conclusion: In most patients receiving chemotherapy for colorectal LMs, a complete response on CT scan does not mean cure.

A variation in liver vascularization was discovered in a 50-year-old man. A single common hepatic artery was found to be responsible for vascularization of the entire liver. This artery was unusual in that it formed the first branch of the superior mesenteric artery, crossing the portal trunk shortly after its origin, and passed in front of the portal vein to reach the hilum of the liver, where it divided into a right and a left branch. This artery was a true common hepatic artery because a gastroduodenal artery emerged from it 2 cm after its origin. A common hepatic artery originating from the mesenteric artery and passing in front of the portal vein has never been described before. The patient had a second anatomical variation: the left gastric artery and the splenic artery arose directly from the aorta, without celiac trunk separation. This observation confirms the importance of carrying out a precise vascular assessment before all types of hepatic or pancreatic surgery, to identify possible variations in the number or trajectory of hepatic arteries.

Objective: : To assess the effects of preoperative systemic chemotherapy on remnant liver parenchyma, liver function, and morbidity after major liver resection for colorectal liver metastases., Background: : Many patients operated upon for colorectal cancer liver metastases receive previous chemotherapy. Whether systemic chemotherapy alters liver parenchyma in such way that it increases the risks of liver resection remains unclear., Patients and Methods: : Among 214 patients who received a liver resection for colorectal liver metastases between 1998 and 2002 in a single institution, 67 who underwent a major liver resection under total hepatic vascular exclusion form the basis of this report. Forty-five patients operated upon after systemic chemotherapy were compared with 22 who did not receive any chemotherapy in the 6 months prior to resection. Postoperative mortality, morbidity, liver function tests, and pathology of the resected liver in the two groups were compared., Results: : There was no postoperative mortality. Values of liver function tests on days 1, 3, 5, and 10 were similar in both groups. Morbidity rate was higher in the chemotherapy group (38% versus 13.5%, P = 0.03). Postoperative morbidity was correlated with the number of cycles of chemotherapy administered before surgery but not to the type of chemotherapy. Preoperative chemotherapy was significantly associated with sinusoidal dilatation, atrophy of hepatocytes, and/or hepatocytic necrosis (49% versus 25%, P = 0.005)., Conclusion: : Prolonged neoadjuvant systemic chemotherapy alters liver parenchyma and increases morbidity after major resection under total hepatic vascular exclusion, but it does not increase operative mortality. This should be taken into consideration before deciding a major liver resection in patients who have received preoperative chemotherapy.

Background: The aim of this case-matched study was to determine the best treatment strategy for patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases., Methods: Between 1997 and 2002, 27 patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases were treated by chemotherapy without initial primary resection (chemotherapy group). These 27 patients were compared with 32 patients matched for age, sex, performance status, primary tumour location, number of liver metastases, nature of irresectable disease and type of chemotherapy, but who were treated initially by resection of primary tumour (resection group)., Results: The 2-year actuarial survival rate was 41 per cent in the chemotherapy group and 44 per cent in the resection group (P = 0.753). In the latter group, the mortality and morbidity rates for primary resection were 0 and 19 per cent (six of 32 patients) respectively. In the chemotherapy group, intestinal obstruction related to the primary tumour occurred in four of 27 patients. The mean overall hospital stay was 11 days in the chemotherapy group and 22 days in the resection group (P = 0.003)., Conclusion: Systemic chemotherapy without resection of the bowel cancer is the option of choice because, for most patients, it is associated with a shorter hospital stay and avoids surgery without a detrimental effect on survival., (Copyright 2005 British Journal of Surgery Society Ltd.)

For a long time, patients with liver metastases from colorectal cancer were considered to be incurable. Over the last 30 years, the benefits of surgical resection and systemic chemotherapy have been established. To date, surgical resection remains the only treatment that can ensure long-term survival and cure in some patient. However, only a minority of patients with liver metastases are amenable to surgery and after resection of liver metastases, recurrences are still observed in two third of patients. Therefore, efforts have been made to increase the number of patients that could be candidates for surgery and to decrease the risk of recurrence after surgical resection. Shrinkage of tumours after administration of pre-operative chemotherapy and the availability of new surgical technique, including portal vein embolization, cryotherapy and radiofrequency ablation, now allows the treatment, with curative intent, of metastases initially considered as non-resectable. Chemotherapy regimens have been developed to decrease the risk of postoperative recurrence.

Pancreatoblastoma is an uncommon pediatric neoplasm with distinct acinar and squamoid cell differentiation. Pancreatoblastoma is exceedingly rare in adults with only ten reported cases. Pancreatoblastoma in adults has a poor prognosis and no survival without recurrence exceeding 30 months has been reported. We report the first adult case of pancreatoblastoma revealed by gastric bleeding due to segmental hypertension. On computed tomography scan, the tumor appeared lobulated and extended from the splenic hilum to the portal vein. Two hypervascular centimetric hepatic metastases were observed in segments III and VII. The patient was operated and a distal pancreatectomy with splenectomy associated with two hepatic wedge resections was performed. The diagnosis of pancreatoblastoma was made on immunohistochemical examination. The patient received 6 cycles of adjuvant therapy. After three years of follow-up, the patient was well with no sign of recurrence on computed tomography scan. This case suggests that in the presence of pancreatic tumor of unknown origin, aggressive management including complete surgical resection and adjuvant chemotherapy should be attempted even in the presence of synchronous liver metastases.

Background: The role of preoperative biliary drainage (PBD) before liver resection in the presence of obstructive jaundice remains controversial. Our patients with proximal duct carcinoma undergo noninvasive assessment followed by rapid laparotomy without PBD if the lesion is deemed resectable., Hypothesis: Our aim was to report operative outcome of these patients and to analyze their specific features by comparison with patients without biliary obstruction who underwent major liver resection., Design: A case-comparison study., Setting: A tertiary care university hospital in a metropolitan area., Patients: Twenty consecutive jaundiced patients underwent major liver resection without PBD. The jaundiced patients were matched with 27 nonjaundiced patients with normal underlying liver selected from a computer bank of 261 patients undergoing liver resections and identical for age, tumor size, type of liver resection, and vascular occlusion., Main Outcome Measure: Postoperative course including mortality, morbidity, transfusion rates, and results of liver function tests., Results: Seventeen jaundiced patients (85%) and 13 nonjaundiced patients (48%) received blood transfusions (P = .03). Morbidity was 50% in jaundiced and 15% in nonjaundiced patients (P = .006), mainly resulting from subphrenic collections and bile leaks occurring only in jaundiced patients. In contrast, there were no significant differences for mortality (5% vs 0%) and liver failure (5% vs 0%). Postoperative changes in liver function test results were comparable between groups., Conclusions: Major liver resections without PBD are safe in most patients with obstructive jaundice. Recovery of hepatic synthetic function is identical to that of nonjaundiced patients. Transfusion requirements and incidence of postoperative complications, especially bile leaks and subphrenic collections, are higher in jaundiced patients. Whether PBD could improve these results remains to be determined.

Charts of 100 consecutive patients who had undergone liver resection, performed by a single surgeon, during the 10 year period from 1983 to 1993 were reviewed. Liver trauma was excluded. The age of the patients ranged from 14 to 78 years, with a mean age of 52 +/- 12.3. Indications for liver resection were malignant tumors in 73 patients and benign disease in another 27 patients. The remnant liver was pathologic in 24 cases (21 cirrhosis, 3 chronic hepatitis). The extent of liver resection was major (> 3 segments) in 51 cases, and minor in 45 cases. Postoperative complications, including death, occurred in 24% of cases. Five complications required reoperation. Hospital mortality was 4%. Multivariate analysis demonstrated two major risk factors of morbidity: intraoperative blood transfusion, and cirrhosis. Age of patients was the only risk factor of mortality. In major resection, four categories of patients were established according to the type of hepatic inflow occlusion. Each group was comparable. Selective vascular clamping (selective control of the hilar vessels to the liver and selective hepatic vein occlusion) decreased the morbidity and post operative liver failure rate (p < 0.05). On the other hand, no correlation was observed between the type of hepatic inflow occlusion and the hospital mortality.