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Papers by Christophe Laurent

Colorectal Disease, 2012

Laparoscopic sphincter-saving surgery has been investigated for rectal cancer but not for tumours... more Laparoscopic sphincter-saving surgery has been investigated for rectal cancer but not for tumours of the lower third. We evaluated the feasibility and efficacy of laparoscopic intersphincteric resection for low rectal cancer. From 1990 to 2007, patients with rectal tumour below 6 cm from the anal verge and treated by open or laparoscopic curative intersphincteric resection were included in a retrospective comparative study. Surgery included total mesorectal excision with internal sphincter excision and protected low coloanal anastomosis. Neoadjuvant treatment was given to patients with T3 or N+ tumours. Recurrence and survival were evaluated by the Kaplan-Meier method and compared using the Logrank test. Function was assessed using the Wexner continence score. Intersphincteric resection was performed in 175 patients with low rectal cancer: 110 had laparoscopy and 65 had open surgery. The two groups were similar according to age, sex, body mass index, ASA score, tumour stage and preoperative radiotherapy. Postoperative mortality (zero) and morbidity (23%vs 28%; P = 0.410) were similar in both groups. There was no difference in 5-year local recurrence (5%vs 2%; P = 0.349) and 5-year disease-free survival (70%vs 71%; P = 0.862). Function and continence scores (11 vs 12; P = 0.675) were similar in both groups. Intersphincteric resection did not alter long-term tumour control of low rectal cancer. The safety and efficacy of the laparoscopic approach for intersphincteric resection are suggested by a similar short- and long-term outcome as obtained by open surgery.

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, Jan 31, 2015

The feasibility and outcome of sphincter-saving resection for rectal cancer were assessed in pati... more The feasibility and outcome of sphincter-saving resection for rectal cancer were assessed in patients previously treated by high-dose radiotherapy for prostate cancer. Between 2000 and 2012, 1066 patients underwent rectal excision for rectal cancer. There were 236 patients treated by conventional radiotherapy (45-Gy) and sphincter-saving resection (Group A) and 12 treated by external-beam radiotherapy (EBRT) for prostate cancer (70-Gy) and sphincter-saving resection (Group B) of whom five had a metachronous and seven a synchronous cancer. The end points were surgical morbidity, pelvic sepsis, reoperation and definitive stoma. Tumour characteristics were similar in both groups. Surgical morbidity (67% vs. 25%, p=0.004), anastomotic leakage (50% vs. 10%, p=0.001), and reoperation (50% vs. 17%, p=0.011) were significantly higher in Group B. Multivariate analyses showed that EBRT for prostate cancer was the only independent factor for anastomotic leakage (OR= 5.12; 95%CI 1.45-18.08; p=0...

We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia ... more We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was found in five out of 30 cases of "multiple benign hepatocytic nodules" collected in our files of the Department of Pathology of the University Hospital of Bordeaux, during the last 12 years. All five cases were women on oral contraceptives. In all cases, the reason for surgery was the discovery, by imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor, possibly an adenoma.

Virchows Archiv : an international journal of pathology, 2003

The aim of this study was to look for vascular abnormalities in the liver of patients with multip... more The aim of this study was to look for vascular abnormalities in the liver of patients with multiple telangiectatic focal nodular hyperplasia. Four patients, all women on oral contraceptives, were included in this study. In none of the cases was the diagnosis of multiple telangiectatic focal nodular hyperplasia made preoperatively. In the nodules, the pathological aspect was quite characteristic with dilated sinusoidal areas surrounding compact areas. Compact areas comprised portal tract-like structures with vessels, mainly thickened arteries, usually amidst an inflammatory reaction. A ductular reaction of varied intensity was present in three cases. The non-nodular liver was grossly normal. However, in rare areas, there were obvious or minor vascular abnormalities looking like minimal abnormalities seen inside telangiectatic nodules. These results seem to support the concept that multiple telangiectatic focal nodular hyperplasia is a non-specific reaction to focal ischemia induced b...

Comparative hepatology, Jan 23, 2003

BACKGROUND: We report our experience of the simultaneous occurrence of adenoma and focal nodular ... more BACKGROUND: We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was found in five out of 30 cases of "multiple benign hepatocytic nodules" collected in our files of the Department of Pathology of the University Hospital of Bordeaux, during the last 12 years. All five cases were women on oral contraceptives. In all cases, the reason for surgery was the discovery, by imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor, possibly an adenoma. RESULTS: Four cases of FNH were discovered by imaging techniques, prior to surgery. Additional small nodules were diagnosed either during surgery or during the slicing of the specimen in 3 cases. Adenoma and the FNH cases identified by imaging techniques were confirmed as such by light microscopy. Some small nodules could not be categorized with certainty because they contained biliary structures without ductular reaction. In...

Comparative hepatology, Jan 26, 2003

BACKGROUND: The typical lesion of focal nodular hyperplasia (FNH) is a benign tumor-like mass cha... more BACKGROUND: The typical lesion of focal nodular hyperplasia (FNH) is a benign tumor-like mass characterized by hepatocytic nodules separated by fibrous bands. The solitary central artery with high flow and the absent portal vein give the lesions their characteristic radiological appearance. The great majority of cases seen in daily practice conform to the above description. Additional small nodules (from 1-2 up to 15-20 mm in diameter) detected by imaging techniques or on macroscopic examination may be difficult to identify as representing FNH if they lack the key features of FNH as defined in larger lesions. The aim of this study was to characterize these small nodules, and to compare their characteristics with those of typical lesions of FNH present in the same specimens. RESULTS: Eight patients underwent hepatic resections for the removal of a mass lesion ("nodule") diagnosed as: FNH (1 patient); nodules of unknown nature (5 patients); or nodules thought to be adenoma o...

Annales De Chirurgie, 2005

Aim of the study. – To report the results of transduodenal excision (TDE) for tumors of the ampul... more Aim of the study. – To report the results of transduodenal excision (TDE) for tumors of the ampulla of Vater.Patients and methods. – From 1998 to 2003, 10 patients underwent a transduodenal excision for presumed benign tumors of the ampulla of Vater. After resection, frozen sections were performed to ensure negative margins.Results. – There was no operative mortality. A postoperative

Surgical Endoscopy, 2005

Background: Although experience of laparoscopic treatment of rectal carcinoma has been reported, ... more Background: Although experience of laparoscopic treatment of rectal carcinoma has been reported, there is no evidence of its oncological safety because most procedures included partial mesorectal excision or abdominoperineal excision and quality of surgery is lacking. The aim of this study was to assess the oncological results of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma. Methods: From 2000 to 2003, 144 patients underwent laparoscopic total mesorectal excision with low colorectal or coloanal anastomosis for mid and low rectal adenocarcinoma. There were 88 men and 56 women, with a median age of 65 years. The tumor was located at 5.5 cm (range 1-12) from the anal verge and was classified uT1T2 in 25 cases and uT3 in 119 cases. One hundred twenty patients received preoperative radiotherapy. Results: Postoperative mortality and morbidity were 1% and 34% respectively. Conversion was 14% (n = 20). Macroscopic assessment of the specimen (n = 92) showed an intact mesorectum in 88% of the cases. The distal margin and the circumferential margin were safe in 98% and 94% of the cases, respectively. A complete microscopic excision, i.e., R0 resection, was achieved in 134 cases (93%). Pathological data were similar to those of an open match group. With a median follow-up of 18 months, there was no port-site recurrence and two patients had local recurrence (1.4%). The 3-year overall and disease-free survival rates were 89% and 77%, respectively.

Gut, 2014

Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated w... more Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated with infection compared with non-HBV-related HCC to understand interactions between viral and hepatocyte genomic alterations and their relationships with clinical features. Frozen HBV (n=86) or non-HBV-related (n=90) HCC were collected in two French surgical departments. Viral characterisation was performed by sequencing HBS and HBX genes and quantifying HBV DNA and cccDNA. Nine genes were screened for somatic mutations and expression profiling of 37 genes involved in hepatocarcinogenesis was studied. HBX revealed frequent non-sense, frameshift and deletions in tumours, suggesting an HBX inactivation selected in HCC. The number of viral copies was frequently lower in tumour than in non-tumour tissues (p=0.0005) and patients with low HBV copies in the non-tumour liver tissues presented additional risk factor (HCV, alcohol or non-alcoholic steato-hepatitis, p=0.006). P53 was the most frequently altered pathway in HBV-related HCC (47%, p=0.001). Furthermore, TP53 mutations were associated with shorter survival only in HBV-related HCC (p=0.02) whereas R249S mutations were identified exclusively in migrants. Compared with other aetiologies, HBV-HCC were more frequently classified in tumours subgroups with upregulation of genes involved in cell-cycle regulation and a progenitor phenotype. Finally, in HBV-related HCC, transcriptomic profiles were associated with specific gene mutations (HBX, TP53, IRF2, AXIN1 and CTNNB1). Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients.

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can b... more Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/ phenotype features. (1) Hepatocyte nuclear factor 1a (HNF1a) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1a-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1a germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating b-catenin mutation was found in 10% of HCA. These b-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress b-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express b-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1a-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.

Hepatology, 2003

ABSTRACT Background & Aims: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/... more ABSTRACT Background & Aims: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1alpha germline mutations with diabetes and liver adenomatosis in 2 families. Methods: Two unrelated patients with liver adenomatosis and harboring HNF-1alpha germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations. Results: In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1alpha in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germ line mutation in HNF-1alpha was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha allele was found in liver tumors in both families. Conclusions: This study describes familial liver adenomatosis and shows the association with germline HNF-1alpha mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.

British Journal of Surgery, 1997

Background The aim of this retrospective study was to compare the risk of local recurrence betwee... more Background The aim of this retrospective study was to compare the risk of local recurrence between two groups of patients with low rectal cancer treated by either abdominoperineal resection (APR) or anterior resection. Methods From 1982 to 1992, 106 low rectal cancers (tumour situated 3-8 cm from the anal verge), of Dukes stage B and C were treated by curative surgery, 52 by APR and 54 by anterior resection. Mean follow-up was 60 months after APR and 50 months after anterior resection. Results The local recurrence rate of low rectal cancer was 16 of 52 (31 per cent) after APR and 15 of 54 (28 per cent) after anterior resection. The risk of local recurrence in univariate and multivariate analysis was not associated with clinical and histological variables, nor with the type of intervention. Conclusion Sphincter-saving resection can be performed for low rectal cancer without an increased risk of local recurrence.

Virchows Archiv, 2002

In every clinician's mind the diagnosis of focal nodular hyperplasia (FNH) is easy, usually made ... more In every clinician's mind the diagnosis of focal nodular hyperplasia (FNH) is easy, usually made by the radiologist. When the diagnosis is doubtful, the nodule is resected, and the correct diagnosis is made by the pathologist. However, the pathologist can also have difficulty in identifying a small nodule as an adenoma or a FNH. To illustrate these difficulties we report the following case.

Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL, 2004

P armi les malades qui ont un cancer colorectal, un tiers va se présenter avec des métastases hép... more P armi les malades qui ont un cancer colorectal, un tiers va se présenter avec des métastases hépatiques synchrones, ce qui représente donc un problème très fréquent de prise en charge thérapeutique. En effet ces tumeurs métastatiques peuvent se présenter sous différentes formes (tumeur primitive symptomatique ou non avec des métastases hépatiques résécables ou non) pour lesquelles les choix thérapeutiques ne sont pas toujours standardisés.

Liver International, 2009

Background and Aims: Glutamine synthetase (GS) is a useful marker in tumour liver pathology, incl... more Background and Aims: Glutamine synthetase (GS) is a useful marker in tumour liver pathology, including hepatocellular adenomas and nodules in cirrhosis. We investigated the use of GS as a marker in various clinical situations, in which FNH diagnosis had been firmly established to determine its contribution to diagnosis. Methods: Seventy-nine cases of resected FNH, all on normal (or occasionally steatotic) livers, were retrieved from our collection. The control group was composed of hepatocellular adenomas and well-differentiated hepatocellular carcinoma. The following stains: H&E, Masson's trichrome, Gordon-Sweet, PAS, perls and immunostains: CK7 and 19, and GS were carried out. FNH was diagnosed based on traditional pathological techniques. In case of uncertainty, particularly with hepatocellular adenoma, additional immunostainings including liver fatty acid-binding protein, serum amyloid A and b-catenin were performed. Results: Glutamine synthetase immunostaining was similar in all FNH cases. Positive GS staining of hepatocytic cytoplasms formed large areas, anastomosed in a 'map-like' pattern, often surrounding hepatic veins, whereas GS was not expressed in hepatocytes close to fibrotic bands containing arteries and ductules. In comparison, hepatocellular adenoma staining was completely different, even in cases of fibrotic bands due to tumour remodelling related to necrosis or haemorrhage. In hepatocellular adenomas or well-differentiated hepatocellular carcinoma presenting bcatenin mutation, GS was positive but with a completely different pattern that appeared diffuse and not 'map-like'. Conclusion: Regardless of the FNH size or steatotic content, GS produced a similar and characteristic pattern and consequently represents a good marker for easily identifying resected FNH from other hepatocellular nodules.

Journal of the American College of Surgeons, 2004

Macroscopic hepatic lymph node involvement is usually a contraindication to hepatic resection. On... more Macroscopic hepatic lymph node involvement is usually a contraindication to hepatic resection. Only a few studies have investigated the impact of hepatic lymph node involvement on survival. The aim of this retrospective study was to assess microscopic hepatic lymph node involvement in resectable colorectal liver metastasis and outcomes in patients with such involvement. From January 1985 to December 2000, 156 patients underwent curative liver resection in association with systematic hepatic lymph node dissection for colorectal liver metastasis. A first analysis was performed to assess the association between hepatic lymph node metastasis and patients' characteristics. A second analysis assessed survival after resection of liver colorectal metastasis by using the Kaplan-Meier method. Twenty-three of the 156 patients (15%) had microscopically involved hepatic lymph nodes. No predictive factor of lymph node metastasis was identified. Multivariate analysis showed that lymph node metastasis, preoperative carcinoembryonic antigen level, number of metastases, and morbidity were factors influencing survival. The 3- and 5-year survival rates of patients with lymph node metastasis were 27% and 5%, respectively, compared with 56% and 43% without lymph node metastasis (p = 0.0001). During resection of liver colorectal metastasis, microscopic lymph node involvement occurred in 15% of the patients and was associated with a poor 5-year survival. Hepatic lymph node dissection should be performed systematically to select high-risk patients.

Journal of the American College of Surgeons, 2005

The incidence of hepatocellular carcinoma (HCC) in cirrhotic and noncirrhotic liver is increasing... more The incidence of hepatocellular carcinoma (HCC) in cirrhotic and noncirrhotic liver is increasing in the world, probably because of the high prevalence of infections by hepatitis B and C viruses. Despite numerous publications on hepatic resection, prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. One hundred eight consecutive patients with HCC in noncirrhotic liver have been treated by hepatic resection in the past 18 years in our center. Clinical, biologic, and histopathologic parameters of these patients were collected. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. Postoperative morbidity and mortality rates were 23% and 6.5%, respectively. The 3- and 5-year disease-free and overall survival rates were 55% and 43%, and 43% and 29%, respectively. Blood transfusion, absence of tumor capsule, and daughter nodules were independently associated with overall survival. But the only risk factors for recurrence were blood transfusion, absence of tumor capsule, daughter nodules, and margin resection < 10 mm. In the treatment of HCC without cirrhosis, hepatectomy remains a safe and legitimate treatment, but longterm results are impaired by a high rate of early recurrence likely related to metastatic dissemination. Only histopathologic factors related to the tumor are predictive of recurrence and overall survival.

Journal of the American College of Surgeons, 2006

The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The i... more The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The impact of postoperative morbidity of TME on longterm survival has never been described. We retrospectively analyzed factors that might influence survival after TME for rectal cancer, including postoperative morbidity. From 1994 to 2001, 300 patients (192 men and 108 women; mean age, 64 years) had TME for rectal cancer. Preoperative radiotherapy was given in 202 patients. Age, gender, tumor height, size and circular invasion of the tumor, pathologic tumor and nodal status, distal and circumferential margins, number of lymph nodes analyzed, type of surgery, postoperative pelvic sepsis, preoperative radiotherapy, and adjuvant chemotherapy were examined; their association with overall and disease-free survival was evaluated by the log-rank test in univariate analysis and by multivariable Cox proportional hazards analysis. Postoperative morbidity was 38% (113 of 300 patients) and included 18% (54 of 300 patients) pelvic sepsis. The local recurrence rate was 6% (18 of 300 patients), and the distant metastasis rate was 24% (73 of 300 patients). Recurrence was three times more frequent distally than locally, including patients with pelvic sepsis The 5-year overall and disease-free survival rates were 72% and 60%, respectively. Independent predictors of overall survival were age older than 64 years (odds ration [OR]=2.19, 95% CI 1.32 to 4.17), pelvic sepsis (OR=2.06, 95% CI 1.10 to 3.87), circumferential surgical margin (OR=3.19, 95% CI 1.67 to 6.09), pathologic tumor (OR=2.69, 95% CI1.23 to 5.88), and nodal status (OR=3.18, 95% CI 1.79 to 5.64). Independent predictors of disease-free survival were pelvic sepsis (OR=2.17, 95% CI 1.31 to 3.58), circumferential surgical margin (OR=2.61, 95 CI 1.52 to 4.49), pathologic tumor (OR=1.82, 95% CI 1.04 to 3.20), and nodal status (OR=2.67, 95% CI 1.68 to 4.23). Patients with pelvic sepsis had a 5-year disease-free survival of 39% compared with 65% without pelvic sepsis (p<0.001). After TME for rectal cancer, pelvic sepsis is a common complication that is associated with increased risk of distant recurrence and decreased longterm survival. Efforts are necessary to decrease postoperative morbidity in surgical treatment of rectal cancer.

Journal of the American College of Surgeons, 2005

The use of chemoradiotherapy for pancreatic cancer has been advocated for its potential ability t... more The use of chemoradiotherapy for pancreatic cancer has been advocated for its potential ability to downstage locally advanced tumors. This article reports our experience with chemoradiotherapy for patients with unresectable, locally advanced pancreatic cancer (superior mesenteric artery or celiac axis encasement). Since 1998, 61 patients with radiographically unresectable, pathologically confirmed pancreatic adenocarcinoma have received standard fractionation radiation therapy (total dose, 45 Gy at 1.8 Gy, 5 d/wk) with chemotherapy, which included a continuous infusion of fluorouracil (5-FU: 650 mg/m(2)/D1-D5 and D21-D25) and cisplatin (80 mg/m(2)/bolus D2 and D22). Patients with tumor response at restaging CT scan underwent surgical exploration to determine whether the tumor was resectable. Thirty-eight of 61 (62%) restaged patients demonstrated a disease progression. Twenty-three patients (38%) had an objective response, with, in all cases, persistence of arterial encasement. Twenty-three patients underwent exploratory operations after chemoradiotherapy, and 13 underwent standard Whipple resection. So 13 of 23 (56%) patients who had exploratory operation, or 23 of 61 (21%) patients, underwent surgical resection. With a median followup of 27 months, median survival for the resected patients was 28 months. Median survival was 11 months in the nonresponder group (n = 38) and 20 months in the group who received a palliative procedure (n = 10). Locally advanced, unresectable pancreatic adenocarcinoma may be downstaged by chemoradiotherapy to allow for surgical resection. Patients whose cancer becomes resectable have a median survival at least comparable with survival after resection for initially resectable pancreatic adenocarcinoma.

Journal of Hepatology, 2003

Colorectal Disease, 2012

Laparoscopic sphincter-saving surgery has been investigated for rectal cancer but not for tumours... more Laparoscopic sphincter-saving surgery has been investigated for rectal cancer but not for tumours of the lower third. We evaluated the feasibility and efficacy of laparoscopic intersphincteric resection for low rectal cancer. From 1990 to 2007, patients with rectal tumour below 6 cm from the anal verge and treated by open or laparoscopic curative intersphincteric resection were included in a retrospective comparative study. Surgery included total mesorectal excision with internal sphincter excision and protected low coloanal anastomosis. Neoadjuvant treatment was given to patients with T3 or N+ tumours. Recurrence and survival were evaluated by the Kaplan-Meier method and compared using the Logrank test. Function was assessed using the Wexner continence score. Intersphincteric resection was performed in 175 patients with low rectal cancer: 110 had laparoscopy and 65 had open surgery. The two groups were similar according to age, sex, body mass index, ASA score, tumour stage and preoperative radiotherapy. Postoperative mortality (zero) and morbidity (23%vs 28%; P = 0.410) were similar in both groups. There was no difference in 5-year local recurrence (5%vs 2%; P = 0.349) and 5-year disease-free survival (70%vs 71%; P = 0.862). Function and continence scores (11 vs 12; P = 0.675) were similar in both groups. Intersphincteric resection did not alter long-term tumour control of low rectal cancer. The safety and efficacy of the laparoscopic approach for intersphincteric resection are suggested by a similar short- and long-term outcome as obtained by open surgery.

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, Jan 31, 2015

The feasibility and outcome of sphincter-saving resection for rectal cancer were assessed in pati... more The feasibility and outcome of sphincter-saving resection for rectal cancer were assessed in patients previously treated by high-dose radiotherapy for prostate cancer. Between 2000 and 2012, 1066 patients underwent rectal excision for rectal cancer. There were 236 patients treated by conventional radiotherapy (45-Gy) and sphincter-saving resection (Group A) and 12 treated by external-beam radiotherapy (EBRT) for prostate cancer (70-Gy) and sphincter-saving resection (Group B) of whom five had a metachronous and seven a synchronous cancer. The end points were surgical morbidity, pelvic sepsis, reoperation and definitive stoma. Tumour characteristics were similar in both groups. Surgical morbidity (67% vs. 25%, p=0.004), anastomotic leakage (50% vs. 10%, p=0.001), and reoperation (50% vs. 17%, p=0.011) were significantly higher in Group B. Multivariate analyses showed that EBRT for prostate cancer was the only independent factor for anastomotic leakage (OR= 5.12; 95%CI 1.45-18.08; p=0...

We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia ... more We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was found in five out of 30 cases of "multiple benign hepatocytic nodules" collected in our files of the Department of Pathology of the University Hospital of Bordeaux, during the last 12 years. All five cases were women on oral contraceptives. In all cases, the reason for surgery was the discovery, by imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor, possibly an adenoma.

Virchows Archiv : an international journal of pathology, 2003

The aim of this study was to look for vascular abnormalities in the liver of patients with multip... more The aim of this study was to look for vascular abnormalities in the liver of patients with multiple telangiectatic focal nodular hyperplasia. Four patients, all women on oral contraceptives, were included in this study. In none of the cases was the diagnosis of multiple telangiectatic focal nodular hyperplasia made preoperatively. In the nodules, the pathological aspect was quite characteristic with dilated sinusoidal areas surrounding compact areas. Compact areas comprised portal tract-like structures with vessels, mainly thickened arteries, usually amidst an inflammatory reaction. A ductular reaction of varied intensity was present in three cases. The non-nodular liver was grossly normal. However, in rare areas, there were obvious or minor vascular abnormalities looking like minimal abnormalities seen inside telangiectatic nodules. These results seem to support the concept that multiple telangiectatic focal nodular hyperplasia is a non-specific reaction to focal ischemia induced b...

Comparative hepatology, Jan 23, 2003

BACKGROUND: We report our experience of the simultaneous occurrence of adenoma and focal nodular ... more BACKGROUND: We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was found in five out of 30 cases of "multiple benign hepatocytic nodules" collected in our files of the Department of Pathology of the University Hospital of Bordeaux, during the last 12 years. All five cases were women on oral contraceptives. In all cases, the reason for surgery was the discovery, by imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor, possibly an adenoma. RESULTS: Four cases of FNH were discovered by imaging techniques, prior to surgery. Additional small nodules were diagnosed either during surgery or during the slicing of the specimen in 3 cases. Adenoma and the FNH cases identified by imaging techniques were confirmed as such by light microscopy. Some small nodules could not be categorized with certainty because they contained biliary structures without ductular reaction. In...

Comparative hepatology, Jan 26, 2003

BACKGROUND: The typical lesion of focal nodular hyperplasia (FNH) is a benign tumor-like mass cha... more BACKGROUND: The typical lesion of focal nodular hyperplasia (FNH) is a benign tumor-like mass characterized by hepatocytic nodules separated by fibrous bands. The solitary central artery with high flow and the absent portal vein give the lesions their characteristic radiological appearance. The great majority of cases seen in daily practice conform to the above description. Additional small nodules (from 1-2 up to 15-20 mm in diameter) detected by imaging techniques or on macroscopic examination may be difficult to identify as representing FNH if they lack the key features of FNH as defined in larger lesions. The aim of this study was to characterize these small nodules, and to compare their characteristics with those of typical lesions of FNH present in the same specimens. RESULTS: Eight patients underwent hepatic resections for the removal of a mass lesion ("nodule") diagnosed as: FNH (1 patient); nodules of unknown nature (5 patients); or nodules thought to be adenoma o...

Annales De Chirurgie, 2005

Aim of the study. – To report the results of transduodenal excision (TDE) for tumors of the ampul... more Aim of the study. – To report the results of transduodenal excision (TDE) for tumors of the ampulla of Vater.Patients and methods. – From 1998 to 2003, 10 patients underwent a transduodenal excision for presumed benign tumors of the ampulla of Vater. After resection, frozen sections were performed to ensure negative margins.Results. – There was no operative mortality. A postoperative

Surgical Endoscopy, 2005

Background: Although experience of laparoscopic treatment of rectal carcinoma has been reported, ... more Background: Although experience of laparoscopic treatment of rectal carcinoma has been reported, there is no evidence of its oncological safety because most procedures included partial mesorectal excision or abdominoperineal excision and quality of surgery is lacking. The aim of this study was to assess the oncological results of laparoscopic total mesorectal excision with sphincter preservation for rectal carcinoma. Methods: From 2000 to 2003, 144 patients underwent laparoscopic total mesorectal excision with low colorectal or coloanal anastomosis for mid and low rectal adenocarcinoma. There were 88 men and 56 women, with a median age of 65 years. The tumor was located at 5.5 cm (range 1-12) from the anal verge and was classified uT1T2 in 25 cases and uT3 in 119 cases. One hundred twenty patients received preoperative radiotherapy. Results: Postoperative mortality and morbidity were 1% and 34% respectively. Conversion was 14% (n = 20). Macroscopic assessment of the specimen (n = 92) showed an intact mesorectum in 88% of the cases. The distal margin and the circumferential margin were safe in 98% and 94% of the cases, respectively. A complete microscopic excision, i.e., R0 resection, was achieved in 134 cases (93%). Pathological data were similar to those of an open match group. With a median follow-up of 18 months, there was no port-site recurrence and two patients had local recurrence (1.4%). The 3-year overall and disease-free survival rates were 89% and 77%, respectively.

Gut, 2014

Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated w... more Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated with infection compared with non-HBV-related HCC to understand interactions between viral and hepatocyte genomic alterations and their relationships with clinical features. Frozen HBV (n=86) or non-HBV-related (n=90) HCC were collected in two French surgical departments. Viral characterisation was performed by sequencing HBS and HBX genes and quantifying HBV DNA and cccDNA. Nine genes were screened for somatic mutations and expression profiling of 37 genes involved in hepatocarcinogenesis was studied. HBX revealed frequent non-sense, frameshift and deletions in tumours, suggesting an HBX inactivation selected in HCC. The number of viral copies was frequently lower in tumour than in non-tumour tissues (p=0.0005) and patients with low HBV copies in the non-tumour liver tissues presented additional risk factor (HCV, alcohol or non-alcoholic steato-hepatitis, p=0.006). P53 was the most frequently altered pathway in HBV-related HCC (47%, p=0.001). Furthermore, TP53 mutations were associated with shorter survival only in HBV-related HCC (p=0.02) whereas R249S mutations were identified exclusively in migrants. Compared with other aetiologies, HBV-HCC were more frequently classified in tumours subgroups with upregulation of genes involved in cell-cycle regulation and a progenitor phenotype. Finally, in HBV-related HCC, transcriptomic profiles were associated with specific gene mutations (HBX, TP53, IRF2, AXIN1 and CTNNB1). Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients.

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can b... more Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/ phenotype features. (1) Hepatocyte nuclear factor 1a (HNF1a) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1a-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1a germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating b-catenin mutation was found in 10% of HCA. These b-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress b-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express b-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1a-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.

Hepatology, 2003

ABSTRACT Background & Aims: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/... more ABSTRACT Background & Aims: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1alpha germline mutations with diabetes and liver adenomatosis in 2 families. Methods: Two unrelated patients with liver adenomatosis and harboring HNF-1alpha germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations. Results: In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1alpha in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germ line mutation in HNF-1alpha was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha allele was found in liver tumors in both families. Conclusions: This study describes familial liver adenomatosis and shows the association with germline HNF-1alpha mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.

British Journal of Surgery, 1997

Background The aim of this retrospective study was to compare the risk of local recurrence betwee... more Background The aim of this retrospective study was to compare the risk of local recurrence between two groups of patients with low rectal cancer treated by either abdominoperineal resection (APR) or anterior resection. Methods From 1982 to 1992, 106 low rectal cancers (tumour situated 3-8 cm from the anal verge), of Dukes stage B and C were treated by curative surgery, 52 by APR and 54 by anterior resection. Mean follow-up was 60 months after APR and 50 months after anterior resection. Results The local recurrence rate of low rectal cancer was 16 of 52 (31 per cent) after APR and 15 of 54 (28 per cent) after anterior resection. The risk of local recurrence in univariate and multivariate analysis was not associated with clinical and histological variables, nor with the type of intervention. Conclusion Sphincter-saving resection can be performed for low rectal cancer without an increased risk of local recurrence.

Virchows Archiv, 2002

In every clinician's mind the diagnosis of focal nodular hyperplasia (FNH) is easy, usually made ... more In every clinician's mind the diagnosis of focal nodular hyperplasia (FNH) is easy, usually made by the radiologist. When the diagnosis is doubtful, the nodule is resected, and the correct diagnosis is made by the pathologist. However, the pathologist can also have difficulty in identifying a small nodule as an adenoma or a FNH. To illustrate these difficulties we report the following case.

Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL, 2004

P armi les malades qui ont un cancer colorectal, un tiers va se présenter avec des métastases hép... more P armi les malades qui ont un cancer colorectal, un tiers va se présenter avec des métastases hépatiques synchrones, ce qui représente donc un problème très fréquent de prise en charge thérapeutique. En effet ces tumeurs métastatiques peuvent se présenter sous différentes formes (tumeur primitive symptomatique ou non avec des métastases hépatiques résécables ou non) pour lesquelles les choix thérapeutiques ne sont pas toujours standardisés.

Liver International, 2009

Background and Aims: Glutamine synthetase (GS) is a useful marker in tumour liver pathology, incl... more Background and Aims: Glutamine synthetase (GS) is a useful marker in tumour liver pathology, including hepatocellular adenomas and nodules in cirrhosis. We investigated the use of GS as a marker in various clinical situations, in which FNH diagnosis had been firmly established to determine its contribution to diagnosis. Methods: Seventy-nine cases of resected FNH, all on normal (or occasionally steatotic) livers, were retrieved from our collection. The control group was composed of hepatocellular adenomas and well-differentiated hepatocellular carcinoma. The following stains: H&E, Masson's trichrome, Gordon-Sweet, PAS, perls and immunostains: CK7 and 19, and GS were carried out. FNH was diagnosed based on traditional pathological techniques. In case of uncertainty, particularly with hepatocellular adenoma, additional immunostainings including liver fatty acid-binding protein, serum amyloid A and b-catenin were performed. Results: Glutamine synthetase immunostaining was similar in all FNH cases. Positive GS staining of hepatocytic cytoplasms formed large areas, anastomosed in a 'map-like' pattern, often surrounding hepatic veins, whereas GS was not expressed in hepatocytes close to fibrotic bands containing arteries and ductules. In comparison, hepatocellular adenoma staining was completely different, even in cases of fibrotic bands due to tumour remodelling related to necrosis or haemorrhage. In hepatocellular adenomas or well-differentiated hepatocellular carcinoma presenting bcatenin mutation, GS was positive but with a completely different pattern that appeared diffuse and not 'map-like'. Conclusion: Regardless of the FNH size or steatotic content, GS produced a similar and characteristic pattern and consequently represents a good marker for easily identifying resected FNH from other hepatocellular nodules.

Journal of the American College of Surgeons, 2004

Macroscopic hepatic lymph node involvement is usually a contraindication to hepatic resection. On... more Macroscopic hepatic lymph node involvement is usually a contraindication to hepatic resection. Only a few studies have investigated the impact of hepatic lymph node involvement on survival. The aim of this retrospective study was to assess microscopic hepatic lymph node involvement in resectable colorectal liver metastasis and outcomes in patients with such involvement. From January 1985 to December 2000, 156 patients underwent curative liver resection in association with systematic hepatic lymph node dissection for colorectal liver metastasis. A first analysis was performed to assess the association between hepatic lymph node metastasis and patients' characteristics. A second analysis assessed survival after resection of liver colorectal metastasis by using the Kaplan-Meier method. Twenty-three of the 156 patients (15%) had microscopically involved hepatic lymph nodes. No predictive factor of lymph node metastasis was identified. Multivariate analysis showed that lymph node metastasis, preoperative carcinoembryonic antigen level, number of metastases, and morbidity were factors influencing survival. The 3- and 5-year survival rates of patients with lymph node metastasis were 27% and 5%, respectively, compared with 56% and 43% without lymph node metastasis (p = 0.0001). During resection of liver colorectal metastasis, microscopic lymph node involvement occurred in 15% of the patients and was associated with a poor 5-year survival. Hepatic lymph node dissection should be performed systematically to select high-risk patients.

Journal of the American College of Surgeons, 2005

The incidence of hepatocellular carcinoma (HCC) in cirrhotic and noncirrhotic liver is increasing... more The incidence of hepatocellular carcinoma (HCC) in cirrhotic and noncirrhotic liver is increasing in the world, probably because of the high prevalence of infections by hepatitis B and C viruses. Despite numerous publications on hepatic resection, prognostic factors for intrahepatic recurrence and survival are not well known for patients with HCC without cirrhosis. One hundred eight consecutive patients with HCC in noncirrhotic liver have been treated by hepatic resection in the past 18 years in our center. Clinical, biologic, and histopathologic parameters of these patients were collected. Risk factors for intrahepatic recurrence and prognostic factors for survival were evaluated by univariate and multivariate analyses. Postoperative morbidity and mortality rates were 23% and 6.5%, respectively. The 3- and 5-year disease-free and overall survival rates were 55% and 43%, and 43% and 29%, respectively. Blood transfusion, absence of tumor capsule, and daughter nodules were independently associated with overall survival. But the only risk factors for recurrence were blood transfusion, absence of tumor capsule, daughter nodules, and margin resection < 10 mm. In the treatment of HCC without cirrhosis, hepatectomy remains a safe and legitimate treatment, but longterm results are impaired by a high rate of early recurrence likely related to metastatic dissemination. Only histopathologic factors related to the tumor are predictive of recurrence and overall survival.

Journal of the American College of Surgeons, 2006

The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The i... more The technique of total mesorectal excision (TME) increases the risk of anastomotic leakage. The impact of postoperative morbidity of TME on longterm survival has never been described. We retrospectively analyzed factors that might influence survival after TME for rectal cancer, including postoperative morbidity. From 1994 to 2001, 300 patients (192 men and 108 women; mean age, 64 years) had TME for rectal cancer. Preoperative radiotherapy was given in 202 patients. Age, gender, tumor height, size and circular invasion of the tumor, pathologic tumor and nodal status, distal and circumferential margins, number of lymph nodes analyzed, type of surgery, postoperative pelvic sepsis, preoperative radiotherapy, and adjuvant chemotherapy were examined; their association with overall and disease-free survival was evaluated by the log-rank test in univariate analysis and by multivariable Cox proportional hazards analysis. Postoperative morbidity was 38% (113 of 300 patients) and included 18% (54 of 300 patients) pelvic sepsis. The local recurrence rate was 6% (18 of 300 patients), and the distant metastasis rate was 24% (73 of 300 patients). Recurrence was three times more frequent distally than locally, including patients with pelvic sepsis The 5-year overall and disease-free survival rates were 72% and 60%, respectively. Independent predictors of overall survival were age older than 64 years (odds ration [OR]=2.19, 95% CI 1.32 to 4.17), pelvic sepsis (OR=2.06, 95% CI 1.10 to 3.87), circumferential surgical margin (OR=3.19, 95% CI 1.67 to 6.09), pathologic tumor (OR=2.69, 95% CI1.23 to 5.88), and nodal status (OR=3.18, 95% CI 1.79 to 5.64). Independent predictors of disease-free survival were pelvic sepsis (OR=2.17, 95% CI 1.31 to 3.58), circumferential surgical margin (OR=2.61, 95 CI 1.52 to 4.49), pathologic tumor (OR=1.82, 95% CI 1.04 to 3.20), and nodal status (OR=2.67, 95% CI 1.68 to 4.23). Patients with pelvic sepsis had a 5-year disease-free survival of 39% compared with 65% without pelvic sepsis (p<0.001). After TME for rectal cancer, pelvic sepsis is a common complication that is associated with increased risk of distant recurrence and decreased longterm survival. Efforts are necessary to decrease postoperative morbidity in surgical treatment of rectal cancer.

Journal of the American College of Surgeons, 2005

The use of chemoradiotherapy for pancreatic cancer has been advocated for its potential ability t... more The use of chemoradiotherapy for pancreatic cancer has been advocated for its potential ability to downstage locally advanced tumors. This article reports our experience with chemoradiotherapy for patients with unresectable, locally advanced pancreatic cancer (superior mesenteric artery or celiac axis encasement). Since 1998, 61 patients with radiographically unresectable, pathologically confirmed pancreatic adenocarcinoma have received standard fractionation radiation therapy (total dose, 45 Gy at 1.8 Gy, 5 d/wk) with chemotherapy, which included a continuous infusion of fluorouracil (5-FU: 650 mg/m(2)/D1-D5 and D21-D25) and cisplatin (80 mg/m(2)/bolus D2 and D22). Patients with tumor response at restaging CT scan underwent surgical exploration to determine whether the tumor was resectable. Thirty-eight of 61 (62%) restaged patients demonstrated a disease progression. Twenty-three patients (38%) had an objective response, with, in all cases, persistence of arterial encasement. Twenty-three patients underwent exploratory operations after chemoradiotherapy, and 13 underwent standard Whipple resection. So 13 of 23 (56%) patients who had exploratory operation, or 23 of 61 (21%) patients, underwent surgical resection. With a median followup of 27 months, median survival for the resected patients was 28 months. Median survival was 11 months in the nonresponder group (n = 38) and 20 months in the group who received a palliative procedure (n = 10). Locally advanced, unresectable pancreatic adenocarcinoma may be downstaged by chemoradiotherapy to allow for surgical resection. Patients whose cancer becomes resectable have a median survival at least comparable with survival after resection for initially resectable pancreatic adenocarcinoma.

Journal of Hepatology, 2003