Philippe Bachellier

Surgical resection of colorectal carcinoma metastases to the liver: A prognostic scoring system to improve case selection, based on 1568 patients

Five‐year survival rates after resection of liver metastases from colorectal carcinoma are close to 25%. Recurrences occur in two‐thirds of the patients after surgery. Selection of patients likely to benefit from surgery remains controversial and subjective.

A Two-Stage Hepatectomy Procedure Combined With Portal Vein Embolization to Achieve Curative Resection for Initially Unresectable Multiple and Bilobar Colorectal Liver Metastases

Objective:To assess outcome after a 2-stage hepatectomy procedure (TSHP) combined with portal vein embolization (PVE) in the treatment of patients with unresectable multiple and bilobar colorectal liver metastases (MBCLM). Background:Patients with MBCLM are often considered for palliative chemotherapy only, due to too small future remnant liver (FRL). Recently, right hepatectomy with simultaneous left liver wedge resections after previous right PVE has been reported in a curative intent. However, the growth of metastatic nodules in FRL after PVE can be more rapid than that of the nontumoral remnant hepatic parenchyma. Therefore, metastases located in the FRL should be ideally resected before PVE. Then, a right (or extended right) hepatectomy can be safely performed during a second-stage hepatectomy. Therefore, we analyzed our experience with the use of TSHP combined with PVE in treatment of MBCLM. Patients and Methods:Between December 1996 and April 2003, 33 patients with unresectable MBCLM were selected for a TSHP. A right or an extended right hepatectomy was planned after treatment of left FRL metastases to achieve a curative resection. The first-stage hepatectomy consisted in a clearance of the left hemiliver by resection or radiofrequency destruction of metastases of the left FRL. Subsequently, a right PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the left hemiliver. Finally, a second-stage hepatectomy was planned to resect the right liver metastases. Results:There was no operative mortality. Post-PVE morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33 patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%, respectively, in the 25 patients in whom the TSHP was completed. Conclusions:In selected patients with initially unresectable MBCLM, a TSHP combined with PVE can be achieved safely with long-term survival similar to that observed in patients with initially resectable liver metastases.

Sinusoidal Injury Increases Morbidity After Major Hepatectomy in Patients With Colorectal Liver Metastases Receiving Preoperative Chemotherapy

Objective:To investigate whether sinusoidal injury (SI) was associated with a worse outcome after hepatectomy in patients with colorectal liver metastases (CRLM). Background:Correlation between SI and oxaliplatin-based chemotherapy (OBC) was recently shown in patients with CRLM. However, it has yet to be fully clarified whether SI affects liver functional reserve and outcome after hepatectomy. Patients and Methods:Between 2003 and 2005, 90 patients with CRLM who underwent an elective hepatectomy after preoperative chemotherapies were included. Diagnosis of SI was established pathologically in the nontumoral liver parenchyma of the resected specimens, and perioperative data were assessed in these patients. Results:OBC was significantly associated with a higher incidence of SI. Preoperative indocyanine green retention rate at 15 minutes (ICG-R15) and postoperative value of total-bilirubin were significantly higher, and hospital stay was significantly longer in patients presenting with SI. Multivariate analysis showed that female gender, administration of 6 cycles or more of OBC, abnormal value of preoperative aspartate aminotransferase >36 IU/L, or abnormal value of preoperative ICG-R15 (>10%) were preoperative factors significantly associated with SI. Among patients undergoing a major hepatectomy, SI was significantly associated with higher morbidity and longer hospital stay. Conclusion:The present study suggests that SI resulted in a poorer liver functional reserve and in a higher complication rate after major hepatectomy. Therefore, female patients who received 6 cycles or more of OBC, or presenting with abnormal preoperative aspartate aminotransferase and ICG-R15 values should be carefully selected before deciding to undertake a major hepatectomy.

Characterization and Clinical Application of Human CD34+ Stem/Progenitor Cell Populations Mobilized into the Blood by Granulocyte Colony‐Stimulating Factor

A phase I study was performed to determine the safety and tolerability of injecting autologous CD34+ cells into five patients with liver insufficiency. The study was based on the hypothesis that the CD34+ cell population in granulocyte colony‐stimulating factor (G‐CSF)‐mobilized blood contains a subpopulation of cells with the potential for regenerating damaged tissue. We separated a candidate CD34+ stem cell population from the majority of the CD34+ cells (99%) by adherence to tissue culture plastic. The adherent and nonadherent CD34+ cells were distinct in morphology, immunophenotype, and gene expression profile. Reverse transcription‐polymerase chain reaction‐based gene expression analysis indicated that the adherent CD34+ cells had the potential to express determinants consistent with liver, pancreas, heart, muscle, and nerve cell differentiation as well as hematopoiesis. Overall, the characteristics of the adherent CD34+ cells identify them as a separate putative stem/progenitor cell population. In culture, they produced a population of cells exhibiting diverse morphologies and expressing genes corresponding to multiple tissue types. Encouraged by this evidence that the CD34+ cell population contains cells with the potential to form hepatocyte‐like cells, we gave G‐CSF to five patients with liver insufficiency to mobilize their stem cells for collection by leukapheresis. Between 1 × 106 and 2 × 108 CD34+ cells were injected into the portal vein (three patients) or hepatic artery (two patients). No complications or specific side effects related to the procedure were observed. Three of the five patients showed improvement in serum bilirubin and four of five in serum albumin. These observations warrant further clinical trials.

Simultaneous resection of colorectal primary tumour and synchronous liver metastases.

The surgical strategy for treatment of synchronous colorectal liver metastases remains controversial. The outcome and overall survival of patients presenting with such metastases, treated either by simultaneous resection or by delayed resection, were evaluated.

Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile

BACKGROUND Whether or not superior mesentericoportal venous resection (SM-PVR) associated with pancreaticoduodenectomy (PD) is safe and worthwhile has not been fully confirmed. The aim of the present study was to investigate results of this surgical procedure performed for pancreatic head and periampullary neoplasms. METHODS As a first analysis, postoperative morbidity and mortality after PD with (n = 31) or without SM-PVR (n = 119) were investigated in 150 patients with pancreatic head and periampullary neoplasms. As a second analysis, rates of margin-negative resection and survival after SM-PVR (n = 21) and without SM-PVR (n = 66) were compared in 87 patients with pancreatic ductal adenocarcinoma of the pancreatic head. In these patients undergoing SM-PVR (n = 21), survival rate was investigated in patients who did (n = 13) and did not (n = 8) undergo a margin-negative resection. RESULTS In the first analysis, duration of surgery and volume of blood transfused perioperatively were higher in patients undergoing SM-PVR. However, mortality, morbidity rates, and mean hospital stay did not differ between patients who did undergo SM-PVR (31 patients, 3.2%, 48.4%, and 22.2 days, respectively) and who did not (119 patients, 2.5%, 47.1%, 25.9 days, respectively). No postoperative death occurred in the recent part of the present study, since 1994, in patients undergoing SM-PVR. In the second analysis of pancreatic ductal adenocarcinoma, rates of margin-negative resection and 2-year survival did not significantly differ between patients who did and did not undergo SM-PVR (62% and 22%, respectively, versus 73% and 24%). In patients undergoing SM-PVR, survival rate was significantly higher for patients undergoing a margin-negative resection (n = 13) than for patients undergoing a macroscopic or microscopic margin-positive resection (n = 8, 2-year survival = 57.1% versus 0%, P <0.05). CONCLUSION PD combined with SM-PVR can be performed safely. This surgical procedure is followed by a promising survival rate and can be recommended in order to obtain a margin-negative resection; however, candidates for SM-PVR should be carefully selected.

Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: A prospective study

BackgroundWe investigated whether hepatic pepticle lymph node (HP-LN) involvement is a more significant prognostic factor and whether HP-LN dissection could be efficient in patients with positive HP-LN involvement.MethodsFrom 1988 to 1998, HP-LN dissection was prospectively performed in 160 patients undergoing hepatectomy for colorectal liver metastases. Survival of patients with HP-LN involvement limited to the hepatoduodenal ligament and retropancreatic portion (area 1) was compared with that of patients with HP-LN involvement spreading over the common hepatic artery and celiac axis (area 2).ResultsHP-LN involvement was detected in 17 patients. The survival rate was significantly lower in patients with HP-LN involvement. HP-LN involvement was the most significant prognostic factor. Survival was significantly higher in patients with HP-LN involvement limited to area 1 than in those with HP-LN involvement spreading over area 2.ConclusionsHP-LN involvement was the most significant prognostic indicator in patients with colorectal liver metastases. Positive LNs of area 1 should no longer be considered an absolute contraindication to liver resection, but in case of area 2 lymph node involvement, liver resection does not seem justified.

AJCC 7th edition of TNM staging accurately discriminates outcomes of patients with resectable intrahepatic cholangiocarcinoma: by the AFC-IHCC-2009 study group

This year, the 7th edition of the AJCC staging manual has for the first time attributed a unique pTNM staging to intrahepatic cholangiocarcinoma (IHCC) that is intended to replace the 2 Western and ideally also the 2 Eastern systems currently in use. This proposal, which has not yet been validated, was tested in the current study.

Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group

Objective:Define the optimal surgical margin in patients undergoing surgery for intrahepatic cholangiocarcinoma (IHCC). Background Data:Surgery is the most effective treatment for IHCC. However, the influence of R1 resection on outcome is controversial and that of margin width has not been evaluated. Methods:We studied 212 patients undergoing curative resection of mass-forming–type IHCC. The respective influences on survival of resection status (R0 vs R1), surgical margin width, pTNM stage, and the latters components were evaluated. Results:Incidence of R1 resection was 24%. Overall, R1 resection was not an independent predictor of survival [odds ratio (OR) 1.2 (0.7–2.1)] in contrast to the pTNM stage [OR 2.10 (1.2–3.5)]. In the 78 pN+ patients, survival was similar after R0 and R1 resections (median: 18 vs 13 months, respectively, P = 0.1). In the 134 pN0 patients, R1 resection was an independent predictor of poor survival [OR 9.6 (4.5–20.4)], as was the presence of satellite nodules [OR 1.9 (1.1–3.2)]. In the 116 pN0 patients with R0 resections, median survival was correlated with margin width (⩽1 mm: 15 months; 2–4 mm: 36 months; 5–9 mm: 57 month; ≥10 mm: 64 month, P < 0.001) and a margin >5 mm was an independent predictor of survival [OR 2.22 (1.59–3.09)]. Conclusion:Patients undergoing surgery for IHCC are at high risk of R1 resections. In pN0 patients, R1 resection is the strongest independent predictor of poor outcome and a margin of at least 5 mm should be created. The survival benefits of resection in pN+ patients and R1 resection in general are very low.

Preoperative contralateral portal vein embolization before major hepatic resection is a safe and efficient procedure: a large single institution experience.

BACKGROUND The aim of this study was to report the results of preoperative contralateral portal vein embolization (PVE) performed in a single institution. METHODS Between January 1997 and March 2006, 146 patients requiring a right or extended right hepatectomy for primary or secondary liver tumors underwent contralateral PVE when the future remnant liver volume (FRL) was less than 30% of total liver. Liver volumes and hepatic function were evaluated before and after PVE. RESULTS Contralateral PVE was performed successfully in 145 patients. In one patient, the catheterization of the left portal branch failed. Complications occurred in 14 patients (10%) including a transitory fever (n = 9), a parenchymal hematoma (n = 1), a mild hemoperitoneum (n = 1), a mesenterico-portal venous thrombosis (n = 1), a pulmonary embolism (n = 1) and a systemic sepsis (n = 1). The prothrombin ratio and the platelet count were significantly lower 3 days after PVE. Insufficient hypertrophy of the FRL was observed in 8 patients, malignant disease progression in 15, and both insufficient hypertrophy and disease progression in 4. The hypertrophy rate of the FRL 4 to 8 weeks after PVE was 47.7 +/- 31.9%. Pathological type of the liver tumor, cirrhosis, diabetes mellitus, and chemotherapy did not affect the volume of the left liver hypertrophy. However, the time required to achieve an adequate liver hypertrophy was significantly shorter in patients with normal liver. One-hundred and fourteen patients (78.6%) subsequently underwent hepatic resection. CONCLUSIONS The results suggest that contralateral PVE is a safe and efficient procedure inducing adequate hypertrophy of the FRL before major liver resection.