Aurélien Dupré

Use of bioresorbable membranes to reduce abdominal and perihepatic adhesions in 2-stage hepatectomy of liver metastases from colorectal cancer: results of a prospective, randomized controlled phase II trial.

Objective:To assess by prospective randomized controlled trial the feasibility and efficacy of using a bioresorbable hyaluronic acid/carboxymethylcellulose membrane (HA membrane) to prevent abdominal and perihepatic adhesions in metastatic colorectal cancer patients requiring 2-stage hepatectomy. Background:Two-stage hepatectomy offers the possibility of long-term survival to selected patients whose liver metastases cannot be removed in a single procedure. However, the second operation is made more difficult by adhesions arising from the first. HA membrane reduces adhesions in gynecologic and abdominal surgery but this is the first trial in hepatectomy. Methods:Fifty-four candidates for 2-stage hepatectomy were randomized at the end of the first procedure to implantation of HA membrane (n = 41) or standard management (n = 13). Thirty patients from the membrane arm and 11 well-matched controls underwent the planned second hepatectomy. Results:Positioning of the HA membranes was feasible in all but one patient and did not increase complications associated with the first hepatectomy. At second hepatectomy, patients in the HA membrane arm required 33% less time than controls to achieve complete liver mobilization (median: 50 vs 75 minutes; primary endpoint). The risk of extensive adhesions was reduced in the HA membrane group (31% had grade 3–4 adhesions vs 55% in controls), as was adhesion severity (17% thick and hypervascular adhesions vs 46%). The proportion of patients with complications at second hepatectomy was higher in the control group (55% vs 23% in the HA membrane group, P = 0.07). Conclusion:Use of 4 HA membranes at the end of first hepatectomy reduced the extent and severity of adhesions and facilitated the second hepatectomy in patients with liver metastases who required a 2-stage hepatectomy. A larger study to confirm these findings is warranted. (NCT01262417)

First Clinical Experience of Intra-Operative High Intensity Focused Ultrasound in Patients with Colorectal Liver Metastases: A Phase I-IIa Study

Background Surgery is the only curative treatment in patients with colorectal liver metastases (CLM), but only 10–20% of patients are eligible. High Intensity Focused Ultrasound (HIFU) technology is of proven value in several indications, notably prostate cancer. Its intra-operative use in patients with CLM has not previously been studied. Preclinical work suggested the safety and feasibility of a new HIFU device capable of ablating volumes of up to 2cm x 2cm in a few seconds. Methods We conducted a prospective, single-centre phase I-IIa trial. HIFU was delivered immediately before scheduled hepatectomy. To demonstrate the safety and efficacy of rapidly ablating liver parenchyma, ablations were performed on healthy tissue within the areas scheduled for resection. Results In total, 30 ablations were carried out in 15 patients. These ablations were all generated within 40 seconds and on average measured 27.5mm x 21.0mm. The phase I study (n = 6) showed that use of the HIFU device was feasible and safe and did not damage neighbouring tissue. The phase IIa study (n = 9) showed both that the area of ablation could be precisely targeted on a previously implanted metallic mark (used to represent a major anatomical structure) and that ablations could be undertaken deliberately to avoid such a mark. Ablations were achieved with a precision of 1–2 mm. Conclusion HIFU was feasible, safe and effective in ablating areas of liver scheduled for resection. The next stage is a phase IIb study which will attempt ablation of small metastases with a 5 mm margin, again prior to planned resection. Trial Registration ClinicalTrials.govNCT01489787

Prise en charge des métastases hépatiques synchrones d'origine colorectale

At time of diagnosis, 10 to 25% of patients with colorectal cancer present synchronous liver metastases. The treatment of such patients remains controversial without any evidence based organization. Therapeutic sequences are discussed including chemotherapy, colorectal surgery, liver resection and even radio-chemotherapy for some rectal cancers. In case of resectable liver metastases, preoperative chemotherapy offers the advantage of earlier treatment of micro-metastases as well as evaluation of tumor responsiveness, which can help shape future therapy. In this setting, different surgical strategies can be chosen (classical staged procedures with colorectal surgery followed by liver surgery, simultaneous resections or liver first approach) depending on the importance of the primary and metastatic tumors. The literature remains limited, but the results of these strategies seem identical in term of postoperative morbidity and long-term survival. Staged procedures are preferred in case of major liver resection. Location of the primary tumor on the low or mid rectum will necessitate preoperative long course chemoradiotherapy and a more complex multidisciplinary organization. For patients with extensive liver metastases, non-resectability must be assessed by experienced surgeon and radiologist before treatment and during chemotherapy. In this group of patients, improved chemotherapy regimen associated with targeted therapies and new surgical strategies (portal vein embolization, ablation, staged hepatectomies…) have improved resection rate (15 to 30-40%) and long-term survival. Treatment organization for the primary tumor remains controversial. Resection of the primary to manage symptoms such as obstruction, perforation or bleeding is advocated. For patients with asymptomatic primary a non-surgical approach permits to begin rapidly chemotherapy and obtain a better control of the disease. On the other hand, initial resection of the primary may avoid complications and the need for urgent surgical procedures. Both of these strategies are practiced without definitive evidence supporting one treatment option over the other.

Validation of clinical prognostic scores for patients treated with curative-intent for recurrent colorectal liver metastases

Scoring systems were developed to stratify patients with colorectal liver metastases considered for liver resection into different risk groups. Such scores have never been evaluated in recurrent liver metastases. The aim of this study was to evaluate whether these scores are applicable to patients with recurrent colorectal liver metastases and treated with curative intent.

Effects of clamping procedures on central venous pressure during liver resection

BACKGROUND Various clamping procedures are used to decrease bleeding during liver resections but their effect on central venous pressure (CVP) remains unclear. The aim of this study was to assess the variations of the CVP during two different clamping procedures. METHODS We retrospectively reviewed 29 patients (19 males, 10 females) who had Pringle maneuver (PM) and clamping of the inferior vena cava below the liver (IVCC) during major liver resections. RESULTS Mean decrease of the CVP after PM, IVCC, and PM+IVCC was 0.84 ± 1.37, 2.17 ± 2.13 and 3.17 ± 2.56 cmH20, respectively (P=0.02, P<0.0001 and P<0.0001, respectively). IVCC was more effective in inducing a decrease of the CVP than PM alone (P<0.05). The combination of both PM and IVCC induced the greatest decrease but not to a level of significance compared to IVCC alone (P=0.25). CONCLUSION IVCC remains the more efficient procedure to lower the CVP. However, although PM is commonly used to control vascular inflow within the liver its significant influence on the CVP could participate to the reduction of bleeding during liver resections.

Previous radiation for prostate neoplasm alters surgical and oncologic outcomes after rectal cancer surgery

Previous radiation for prostate cancer (PC) contra‐indicates neoadjuvant chemoradiotherapy for rectal cancer (RC) because of risk of cumulative radiation dose toxicity. Postoperative outcomes after proctectomy have not been well studied in these patients who did not receive optimal treatment.

Giant mucinous cystic adenoma with pancreatic atrophy mimicking dorsal agenesis of the pancreas

Mucinous cystic adenoma (MCA) of the pancreas is a rare benign cystic tumor with ovarian-like stroma and lack of communication with the pancreatic ductal system. The ovarian tissue is incorporated from the left gonad within the dorsal pancreas during embryogenesis. Consequently, congenital dorsal agenesis of the pancreas (DAP) cannot be associated with MCA. We report the case of a giant MCA associated with atrophy of the dorsal pancreas mimicking complete DAP. Pancreato-magnetic resonance imaging failed to identify the dorsal pancreas but the absence of diabetes mellitus and compression of the splenic vein with major tributaries rectified the diagnosis of secondary atrophy of the distal pancreas. Unusual proximal location of the cyst in the pancreas may have induced chronic obstruction of both the dorsal pancreatic duct and the splenic vein, with secondary atrophy of the distal pancreas.

Development of a toroidal high-intensity focused ultrasound transducer for the treatment of pancreatic tumors. In vivo study of the safety and efficacy in a porcine model

Pancreatic ductal adenocarcinoma (PDA) is the most frequent primary malignancy of the pancréas. PDA has increased in incidence during the last decade and now constitutes the fourth leading cause of cancer mortality. New focal destruction technologies such as high-intensity focused ultrasound (HIFU) may improve the prognosis of pancreatic ductal adenocarcinoma. Given the inconvenience and disadvantages of extracorporeal HIFU, we developed an intraoperative HIFU probe, initially designed for the treatment of colorectal liver metastasis, with encouraging results. The principal interest lies in the possibility of treating hepatic parenchyma in a short period. The intraoperative HIFU probe designed for the treatment of liver tumors could be used for pancreatic tumors. The aim of this preclinical study was to determine the safety and efficacy of intraoperative HIFU in vivo on pancreatic tissue in a porcine model.

A Normal Preoperative Lipase Serum Level Is an Easy and Objective Risk Factor of Pancreatic Fistula After Pancreaticoduodenectomy

Objectives The evaluation of the risk of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy is crucial to optimize perioperative strategies. Many risk factors of POPF have been identified and were included in scores. Performances of these scores have to be improved because of the use of subjective and/or intraoperative factors. We tried to identify new risk factors of POPF that could improve the performance of validated scores. Methods We analyzed data from a prospective database of 191 consecutive patients who underwent a pancreaticoduodenectomy. Recorded data included a comprehensive inventory of pre-, intra- and postoperative clinical, biological and radiological data. Results The rate of POPF was significantly increased in patients with a normal preoperative lipase serum level (LSL) (29.8% vs 6.8%; P = 0.001). After multivariate analysis, a normal preoperative LSL was a strong independent risk factor of both POPF (odds ratio, 7.06; P = 0.001) and clinically relevant POPF (odds ratio, 3.11; P = 0.036). The addition of the normality of the preoperative LSL to the Fistula Risk Score significantly improved its performance (P < 0.001). Conclusions A normal preoperative LSL was a strong, easy, and objective preoperative risk factor of POPF. Its addition to the Fistula Risk Score improved its performance and allows a more accurate evaluation of the risk of POPF.

Thermal Ablation of the Pancreas With Intraoperative High-Intensity Focused Ultrasound: Safety and Efficacy in a Porcine Model

Objective New focal destruction technologies such as high-intensity focused ultrasound (HIFU) may improve the prognosis of pancreatic ductal adenocarcinoma. Our objectives were to demonstrate the safety and efficacy of intraoperative pancreatic HIFU ablation in a porcine model. Methods In a porcine model (N = 12), a single HIFU ablation was performed in either the body or tail of the pancreas, distant to superior mesenteric vessels. All animals were sacrificed on the eighth day. The primary objective was to obtain an HIFU ablation measuring at least 1 cm without premature death. Results In total, 12 HIFU ablations were carried out. These ablations were performed within 160 seconds and on average measured 20 (15–27) × 16 (8–26) mm. The primary objective was fulfilled in all but 1 pig. There were no premature deaths or severe complications. High-intensity focused ultrasound treatment was associated with a transitory increase in amylase and lipase levels, and pseudocysts were observed in half of the pigs without being clinically apparent. All ablations were well delimited at both gross and histological examinations. Conclusions Intraoperative thermal destruction of porcine pancreas with HIFU is feasible. Reproducibility and safety have to be confirmed when applied close to mesenteric vessels and in long-term preclinical studies.