Jean-François Gigot

Laparoscopic liver resection of benign liver tumors: Results of a multicenter European experience

Objective: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection for benign liver tumors in a multicenter setting. Background: Despite restrictive, tailored indications for resection in benign liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors. Methods: A retrospective study was performed in 18 surgical centres in Europe regarding their experience with laparoscopic resection of benign liver tumors. Detailed standardized questionnaires were used that focused on patients characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome. Results: From March 1992 to September 2000, 87 patients suffering from benign liver tumor were included in this study: 48 patients with focal nodular hyperplasia (55%), 17 patients with liver cell adenoma (21%), 13 patients with hemangioma (15%), 3 patients with hamartoma (3%), 3 patients with hydatid liver cysts (3%), 2 patients with adult polycystic liver disease (APLD) (2%), and 1 patient with liver cystadenoma (1%). The mean size of the tumor was 6 cm, and 95% of the tumors were located in the left liver lobe or in the anterior segments of the right liver. Liver procedures included 38 wedge resections, 25 segmentectomies, 21 bisegmentectomies (including 20 left lateral segmentectomies), and 3 major hepatectomies. There were 9 conversions to an open approach (10%) due to bleeding in 45% of the patients. Five patients (6%) received autologous blood transfusion. There was no postoperative mortality, and the postoperative complication rate was low (5%). The mean postoperative hospital stay was 5 days (range, 2–13 days). At a mean follow-up of 13 months (median, 10 months; range, 2–58 months), all patients are alive without disease recurrence, except for the 2 patients with APLD. Conclusions: Laparoscopic resection of benign liver tumors is feasible and safe for selected patients with small tumors located in the left lateral segments or in the anterior segments of the right liver. Despite the use of a laparoscopic approach, selective indications for resection of benign liver tumors should remain unchanged. When performed by expert liver and laparoscopic surgeons in selected patients and tumors, laparoscopic resection of benign liver tumor is a promising technique.n

FDG-PET improves the staging and selection of patients with recurrent colorectal cancer

Abstract Whole-body fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has proved effective in the diagnosis and staging of recurrent colorectal cancer. In this study, we analysed how PET affects the management of patients with recurrent colorectal cancer by permitting more accurate selection of candidates for curative resection. The data of 79 patients with known or suspected recurrent colorectal cancer were analysed. Conventional imaging modalities (CIM) and PET results were compared with regard to their accuracy in determining the extent and the resectability of tumour recurrence. Recurrence was demonstrated in 68 of the 79 patients. The data indicate that PET was superior to CIM for detection of recurrence at all sites except the liver. Based on the CIM+PET staging, surgery with curative intent was proposed in 39 patients and was indeed achieved in 31 of them (80%). PET was more accurate than CIM alone in predicting the resectability or non-resectability of the recurrence (82% vs 68%, P=0.02). It is concluded that whole-body FDG-PET is highly sensitive for both the diagnosis and the staging of patients with recurrent colorectal cancer. Its use in conjunction with conventional imaging procedures results in a more accurate selection of patients for surgical treatment with curative intent.

Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine needle aspiration: high reproducibility and inter-observer agreement of the Ki-67 labelling index

Assessment of proliferation by the Ki‐67 labelling index (Ki67‐LI) is an important parameter of pancreatic neuroendocrine tumour (pNET) prognosis on resection specimens. Ki67‐LI values for grading are not fully established on endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA). The aim of the study was to determine the accuracy of Ki67‐LI on EUS‐FNA to predict a final grade of pNET and to analyse the relationship between cytological grading and progression‐free survival (PFS).

Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets

AbstractBackgroundThe molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.MethodsnMultiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.ResultsnThe majority of patients (61.5xa0%) had no genetic mutation identified. Among the 77 patients (38.5xa0%) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5xa0%: IDH1 (15.5xa0%) and KRAS (8.6xa0%). Other genetic mutations were identified in very low frequency: BRAF (4.9xa0%), IDH2 (4.5xa0%), PIK3CA (4.3xa0%), NRAS (3.1xa0%), TP53 (2.5xa0%), MAP2K1 (1.9xa0%), CTNNB1 (0.6xa0%), and PTEN (0.6xa0%). Among patients with an IDH1-mutant tumor, approximately 7xa0% were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4xa0%). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both Pxa0<xa00.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.ConclusionsMost somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.

Surgical management of acute cholecystitis: results of a 2-year prospective multicenter survey in Belgium

BackgroundLaparoscopic cholecystectomy is considered nowadays as the standard management of acute cholecystitis (AC). However, results from multicentric studies in the general surgical community are still lacking.MethodsA prospective multicenter survey of surgical management of AC patients was conducted over a 2-year period in Belgium. Operative features and patients’ clinical outcome were recorded. The impact of independent predictive factors on the choice of surgical approach, the risk of conversion, and the occurrence of postoperative complications was studied by multivariate logistic regression analysis.ResultsFifty-three surgeons consecutively and anonymously included 1,089 patients in this prospective study. A primary open approach was chosen in 74 patients (6.8%), whereas a laparoscopic approach was the first option in 1,015 patients (93.2%). Independent predictive factors for a primary open approach were previous history of upper abdominal surgery [odds ratio (OR) 4.13, pxa0<xa00.001], patient age greater than 70xa0years (OR 2.41, pxa0<xa00.05), surgeon with more than 10xa0years’ experience (OR 2.08, pxa0=xa00.005), and gangrenous cholecystitis (OR 1.71, pxa0<xa00.05). In the laparoscopy group, 116 patients (11.4%) required conversion to laparotomy. Overall, 38 patients (3.5%) presented biliary complications and 49 had other local complications (4.5%). Incidence of bile duct injury was 1.2% in the whole series, 2.7% in the open group, and 1.1% in the laparoscopy group. Sixty patients had general complications (5.5%). The overall mortality rate was 0.8%. All patients who died were in poor general condition [American Society of Anesthesiologists (ASA) III or IV].ConclusionsAlthough laparoscopic cholecystectomy is currently considered as the standard treatment for acute cholecystitis, an open approach is still a valid option in more advanced disease. However, overall mortality and incidence of bile duct injury remain high.

Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma

BACKGROUNDnCholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers the only chance for cure. When surgery is unfeasible, chemotherapy is the backbone of treatment. The combined administration of cisplatin and gemcitabine is considered standard of care. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. hENT1 expression is associated with an increased survival for patients receiving gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive of response to gemcitabine.nnnAIMnTo determine whether there is a correlation between the expression of hENT1 and disease outcome in CC.nnnMETHODSnA retrospective study on 43 patients treated at our centre with a locally advanced or metastatic CC, who received first line treatment with gemcitabine, was performed.nnnRESULTSnFor the whole population, median Progression Free Survival (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7-5.3 months) and 10.0 months (95%CI 6.8-13.2 months), respectively. From the 26 samples available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for low versus high staining respectively (p = 0.012). The median OS were 5.0 versus 11.0 months for low versus high staining, respectively (p = 0.036). On multivariate analysis, hENT1 expression was the single independent predictive factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p = 0.046).nnnCONCLUSIONnIn this study we show the potential of hENT1 expression as a predictor of outcome in CC treated with gemcitabine. Larger studies are necessary to confirm these promising results.

Tumor size predicts vascular invasion and histologic grade among patients undergoing resection of intrahepatic cholangiocarcinoma.

The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5xa0cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3xa0cm, 3.6xa0%; 3–5xa0cm, 24.7xa0%; 5–7xa0cm, 38.3xa0%; 7–15xa0cm, 32.9xa0%, ≥15xa0cm, 55.6xa0%; (pu2009<u20090.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3xa0cm, 9.7xa0%; 3–5xa0cm, 19.8xa0%; 5–7xa0cm, 24.2xa0%; 7–15xa0cm, 21.1xa0%; >15xa0cm, 31.6xa0% (pu2009=u20090.04). The presence of perineural invasion (odds ratio [OR]u2009=u20092.98) and regional lymph node metastasis (ORu2009=u20094.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5xa0cm (both pu2009<u20090.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC.

Histological and Immunohistochemical Revision of Hepatocellular Adenomas: A Learning Experience

Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA) recognizing HNF1α-inactivated HCA (H-HCA), inflammatory HCA (IHCA), and β-catenin-activated HCA (b-HCA). We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25%) characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5%) showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%), b-HCA with GS and β-catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5%) remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/HNF1α-inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.

Liver transplantation with preservation of the inferior vena cava in case of symptomatic adult polycystic disease.

Adult polycystic liver disease (APLD) is a rare disorder of the liver parenchyma, the treatment of which is still controversial. Conservative surgery may have a significant morbidity and is often ineffective in the long run. Liver replacement may be indicated in case of incapacitating hepatomegaly. Patients (one male, five females) undergoing liver transplantation for symptomatic APLD is presented in this study. The particular nature of this series is the fact that successful transplantation was performed in all cases with preservation of the recipients inferior vena cava and without use of veno‐venous bypass despite massive hepatomegaly and previous extensive liver surgery (in three cases). There was minimal morbidity and no mortality. All patients have excellent quality of life with a median follow‐up of 41u2003months (range: 12–58) as testified by a median Karnofsky score of 90% (range: 80–100%).

Résections pancréatiques par laparoscopie

The faisability of laparoscopic pancreatic resection has been demonstrated. However, the real clinical benefit for the patients remains questioned. The best indication for a laparoscopic approach appears to be the resection of benign or neuro-endocrine tumors without a need for pancreato-enteric reconstruction (i.e enucleation or distal pancreatectomy). The use of the laparoscopic approach for malignant tumors still remains controversial. The benefits of minimally invasive surgery are clearly correlated with the successful management of the pancreatic stump. Pancreatic related complication rate (fistula and collection) is 15% when using pancreatic transection with a laparoscopic endostappler