Papers by Isabelle Sourrouille
Oncotarget, 2015
Mismatch-repair (MMR)-deficient cells show increased in vitro tolerance to thiopurines because th... more Mismatch-repair (MMR)-deficient cells show increased in vitro tolerance to thiopurines because they escape apoptosis resulting from MMR-dependent signaling of drug-induced DNA damage. Prolonged treatment with immunosuppressants including azathioprine (Aza), a thiopurine prodrug, has been suggested as a risk factor for the development of late onset leukemias/lymphomas displaying a microsatellite instability (MSI) phenotype, the hallmark of a defective MMR system. We performed a dose effect study in mice to investigate the development of MSI lymphomas associated with long term Aza treatment. Over two years, Aza was administered to mice that were wild type, null or heterozygous for the MMR gene Msh2. Ciclosporin A, an immunosuppressant with an MMR-independent signaling, was also administered to Msh2wt mice as controls. Survival, lymphoma incidence and MSI tumor phenotype were investigated. Msh2+/- mice were found more tolerant than Msh2wt mice to the cytotoxicity of Aza. In Msh2+/- mice, Aza induced a high incidence of MSI lymphomas in a dose-dependent manner. In Msh2wt mice, a substantial lifespan was only observed at the lowest Aza dose. It was associated with the development of lymphomas, one of which displayed the MSI phenotype, unlike the CsA-induced lymphomas. Our findings define Aza as a risk factor for an MSI-driven lymphomagenesis process.
Diseases of the colon and rectum, 2013
Rectal surgery via a single-port access is complex with unknown benefits. This study aimed to com... more Rectal surgery via a single-port access is complex with unknown benefits. This study aimed to compare the short-term outcome between single-port and multiport procedures. We undertook a retrospective analysis of prospectively collected data in a large, tertiary care cancer center in France. From November 2008 to June 2012, 45 patients underwent a sphincter-saving rectal resection through a single-port (n = 13) or a multiport (n = 32) approach. The single-port approach used an abdominal single port (n = 6) alone or a combined abdominal and transanal single port (n = 7). This study analyzed the morbidity, mortality, pain, and quality of the oncologic resection. The groups had a similar median operative time (290 vs 280 minutes, p = 0.54) and conversion rates (8% vs 6%, p = 0.90). No mortality occurred, and there was no difference in major morbidity (23% vs 16%, p = 0.50), anastomotic leakage (8% vs 9%, p = 1), or the length of the hospital stay (12 vs 14 days, p = 0.23). The median pa...
Diseases of the Colon & Rectum, 2015
Perineal soft tissue tumors are rare, so that little is known about their management and the outc... more Perineal soft tissue tumors are rare, so that little is known about their management and the outcome of treatment. The aim of this study is to describe the presentation, management, and outcome of the surgical treatment of soft tissue tumors and to provide a final decision algorithm. This is a retrospective study. The study was conducted in a single tertiary care hospital with a dedicated unit on sarcoma. Fifty-one consecutive patients from 1998 to 2013 were included. The primary outcomes measured are patient demographics, treatment decisions, and outcome of surgical treatment. Forty-nine patients presented with a primary soft tissue tumor, and 2 underwent simple excisions for isolated metastases. The median tumor size was 75 mm (50-110). Symptoms were nonspecific, and MRI had insufficient specificity for malignancy so that a preoperative biopsy was systematically performed according to European Society for Medical Oncology and National Comprehensive Cancer Network soft tissue tumor guidelines. Six benign soft tissue tumors (3 lipomas, 3 leiomyomas), 16 intermediate soft tissue tumors (12 aggressive angiomyxoma, 4 desmoid tumors), and 27 sarcomas were identified. Treatments and surgery were tailored from the beginning according to histology. All but 1 benign soft tissue tumor were treated by 'shelling out.' Aggressive angiomyxoma were treated with en bloc resection sparing uninvolved organs. Nonsurgical treatments were our first choice for desmoid tumors. Wide en bloc surgery was planned for all sarcomas (n = 27) after the induction treatment for 16 patients (chemotherapy, n = 12; radiotherapy, n = 4). In the sarcoma group, the 5-year estimated metastasis-free, local recurrence-free, and overall survival rates were 68.1% (95% CI, 50.7-91.5), 84.7% (95% CI, 66.7-100), and 85.7% (95% CI, 71.8-100). In the benign and intermediate tumor groups, there were no deaths, local recurrences, or progression. This study was limited by the small number of patients, given the rarity of this disease in the perineum. We provide useful indications for the best strategy necessary to treat these rare tumors located in a complex site.
Journal de Chirurgie Viscérale, 2014
ABSTRACT Objectif Décrire les résultats de la chirurgie par cytoréduction maximale (CCM) chez les... more ABSTRACT Objectif Décrire les résultats de la chirurgie par cytoréduction maximale (CCM) chez les patients atteints de carcinose péritonéale (CP) dont le primitif est une tumeur neuroendocrine (TNE) et comparer la survie des patients, traités avec ou sans chimiothérapie hyperthermique (CHIP). Contexte Il n’existe actuellement aucune recommandation dans la littérature concernant la CCM dans le traitement de la CP des TNE. Pourtant, ces métastases sont associées à un mauvais facteur pronostic de survie. Matériel et méthodes Étude rétrospective incluant 41 patients traités par CCM de leurs CP-TNE entre 1994 et 2012. Parmi eux, 28 patients ont eu une CHIP associés au traitement par CCM entre 1994 et 2007 et 13 patients ont été traités uniquement par chirurgie entre 2008 et 2012. Résultats La mortalité était de 2 % et la morbidité de 56 %. La survie globale (OS) à 5 ans était de 69 % et de 52 % à 10 ans. La survie sans récidive (DFS) à 5 ans était de 17 % et de 6 % à 10 ans. À 5 ans, la récidive des CP concernait 47 % des patients. L’OS n’était pas différente entre les patients traités avec ou sans CHIP. En revanche, la DFS était plus importante dans le groupe des patients traités par CHIP (p = 0,018). Conclusion La CCM des CP des TNE est techniquement possible dans la plupart des cas et semble augmenter la survie. Nous n’avons pas pu déterminer dans cette étude si l’ajout d’une CHIP à la CCM augmente la survie des ces patients.
Transplantation Journal, 2010
Surgery, 2014
Aim. To report the results of complete cytoreductive surgery (CCRS) of peritoneal metastases from... more Aim. To report the results of complete cytoreductive surgery (CCRS) of peritoneal metastases from neuroendocrine tumor (NET) and to compare patients treated with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Background. Aggressive management of peritoneal metastases from NET (in most of the cases associated with other types of metastases) has not been addressed in the literature, but these metastases affect overall survival. Patients and methods. From 1994 to 2012, 41 patients underwent CCRS, with HIPEC (n = 28) from 1994 to 2007 but without HIPEC (n = 13) from 2008 to 2012. Liver metastases were treated during the same operative procedure in 66% of the patients. Results. Mortality was 2% and morbidity 56%. Overall survival at 5 and 10 years was 69% and 52%, respectively, and disease-free survival at 5 and 10 years was 17% and 6%, respectively. At 5 years, peritoneal metastases and liver metastases recurred in 47% and in 66% of cases, respectively. Overall survival was not different between patients treated with or without HIPEC, but disease-free survival was greater in the HIPEC group (P = .018), mainly because of fewer lung and bone metastases. Conclusion. CCRS of peritoneal metastases from a NET is feasible in most of the patients and seems to increase survival rates. We were unable to determine whether adding HIPEC had a positive or a negative impact. (Surgery 2014;155:5-12.) From the
Saudi Journal of Gastroenterology, 2013
Peritoneal carcinomatosis (PC) is a pernicious event associated with a dismal prognosis. Complete... more Peritoneal carcinomatosis (PC) is a pernicious event associated with a dismal prognosis. Complete cytoreductive surgery (CCRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is able to yield an important survival benefit but at the price of a risky procedure inducing potentially severe complications. Postoperative peritonitis after abdominal surgery occurs mostly when the digestive lumen and the peritoneum communicate but in rare situation, no underlying digestive fistula can be found. The aim of this study was to report this situation after CCRS plus HIPEC, which has not been described yet and for which the treatment is not yet well defined. Between 1994 and 2012, 607 patients underwent CCRS plus HIPEC in our tertiary care center and were retrospectively analyzed. Among 52 patients (9%) reoperated for postoperative peritonitis, no digestive fistula was found in seven (1%). All had a malignant peritoneal pseudomyxoma with an extensive disease (median Peritoneal Cancer Index: 27). The median interval between surgery and reoperation was 8 days [range: 3-25]. Postoperative mortality was 14%. Five different bacteriological species were identified in intraoperative samples, most frequently Escherichia coli (71%). The infection was monobacterial in 71%, with multidrug resistant germs in 78%. Postoperative peritonitis without underlying fistula after CCRS plus HIPEC is a rare entity probably related to bacterial translocation, which occurs in patients with extensive peritoneal disease requiring aggressive surgeries. The principles of treatment do not differ from that of other types of postoperative peritonitis.
HPB, 2013
Pancreaticoduodenectomy (PD) is associated with high morbidity, in part as a result of infectious... more Pancreaticoduodenectomy (PD) is associated with high morbidity, in part as a result of infectious complications increased by preoperative bile contamination. The aim of the present study was to assess the effect on the incidence of infectious complications of short-term antimicrobial therapy (AMT) in high-risk patients. Patients with a high risk for positive intraoperative bile culture (i.e. those with ampulloma or pancreatic adenocarcinoma with preoperative endoscopic procedures) (high-risk group, n = 99) were compared with low-risk patients (i.e. those with pancreatic adenocarcinoma without preoperative endoscopic procedures) (low-risk group, n = 76). The high-risk group received a 5-day course of perioperative AMT secondarily adapted to the bile antibiogram. The low-risk group received only the usual antimicrobial prophylaxis. Positive bile cultures were significantly more frequent in high-risk patients (81% versus 12%; P < 0.001). The overall rate of infectious complications was lower in the high-risk group (29% versus 46%; P = 0.018). The statistically significant decrease in the rate of infectious complications reflected reduced rates of urinary tract infections, pulmonary infections and septicaemia. Rates of wound infection (3% versus 5%; P = 0.639) and intra-abdominal abscess (7% versus 7%; P = 0.886) were similar in the high- and low-risk groups, as was the need for curative AMT. This exploratory study suggests that a postoperative short course of AMT in patients at high risk for biliary contamination reduces the overall rate of infectious complications after PD. The adaptation of perioperative antimicrobial policy to the patient's risk for bile contamination seems promising and should be further evaluated.
Familial Cancer, 2013
Some patients happen to have a colorectal cancer with microsatellite instability (MSI), but witho... more Some patients happen to have a colorectal cancer with microsatellite instability (MSI), but without any alteration in Mismatch Repair (MMR) system (germline mutation/promoter methylation). We aimed to identify the mechanism of inactivation of MMR genes in those cases. We studied 18 patients with MSI CCR and loss of expression of a MMR protein. DNA was extracted from tumoral and normal colonic material. We studied the 3 main MMR genes in tumors, by sequencing and large rearrangement analysis, and looked for mosaicism. Seven patients lost expression of MLH1, we found 1 mutation in the tumor for 3 patients and 2 mutations in one. Eight patients lost expression of MSH2: we found 1 mutation in 2 patients and 2 mutations in four. In the 5 cases with 2 hits, MSI was due to double somatic hits (n = 3), mosaicism (n = 1) and missed germline mutation (n = 1). Mosaicism was confirmed by HRM analysis, and by finding a germline mutation in one patient's son. We could explain MSI in the tumors of 5 patients (27.8 %). Their follow up and family's surveillance could be adjusted, as the sporadic cases don't require intensive surveillance. We describe the first case of somatic mosaicism after de novo mutation in MSH2.
The Annals of Thoracic Surgery, 2011
chronic pain are reported by 45% of patients when monitored long term . To date, there is no opti... more chronic pain are reported by 45% of patients when monitored long term . To date, there is no optimal treatment option ("gold standard") for surgical treatment of patients with complete sternum resection. Prosthetic grafts manufactured from Teflon in polytetrafluoroethylene (PTFE) and polyprene in polypropylene are associated with synthetic reaction and an increased risk of infection.
Journal of Surgical Oncology, 2013
Recent changes in adjuvant therapies improved the prognosis of metastatic colorectal cancers. Cur... more Recent changes in adjuvant therapies improved the prognosis of metastatic colorectal cancers. Curative resection may be considered, even for both pulmonary and hepatic metastases, but prognostic factors are not well identified. From 1995 to 2010, 69 patients had curative resection of pulmonary metastases of colorectal cancer; 31 had also hepatic metastases. Pulmonary and hepatic resection occurred in 2 steps (87%). We studied overall and disease-free survival and prognostic factors. Primary tumor location was the rectum in 10 cases (32%). Pulmonary metastases were synchronous in 5 (16%) and bilateral in 6 (19%). One patient (3%) died after pulmonary surgery. One (3%) had positive surgical margins for pulmonary metastases. Median overall survival was 44 months (5-year rate = 36%); median disease-free survival was 22 months (5-year rate = 10%). Factors linked to impaired survival were rectal primary tumor (P = 0.04) and bilateral pulmonary metastases (P = 0.02) for overall survival, and pulmonary metastase ≥ 20 mm (P = 0.04) for disease-free survival. When associated to adjuvant therapy, complete resection of pulmonary and hepatic metastases of colorectal cancer allows long-term survival in one third of the patients.
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Papers by Isabelle Sourrouille