Five days of postoperative antimicrobial therapy decreases infectious complications following pancreaticoduodenectomy in patients at risk for bile contamination

AbstractObjectivesPancreaticoduodenectomy (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.MethodsPatients 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.ResultsPositive 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.ConclusionsThis 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

The inactivation of O6-methylguanine-DNA methyltransferase (MGMT) constitutes an initiating step in MSI carcinogenogenesis

L’inactivation du système de réparation des mésappariements de l’ADN (MisMatch Repair, MMR) favorise un processus oncogénique d’instabilité des microsatellites du génome (MicroSatellite Instability, MSI). Les cancers colorectaux (CCR) MSI peuvent s’observer dans un contexte familial (syndrome de Lynch, SL) ou sporadique. Les cryptes MMR déficientes (MMR-Deficient Crypt Foci, MMR-DCF), lésions de la muqueuse non tumorale perdant l’expression d’une protéine MMR, pourraient constituer un événement prénéoplasique de la carcinogénèse colorectale MSI chez les patients SL. Dans certains CCR MSI, les cas «Lynch-like», le diagnostic de SL ne peut être posé avec certitude car aucune mutation germinale pathogénique MMR n’est identifiée, malgré une forte suspicion clinico-phénotypique. Nous avons confirmé que les MMR-DCF ne s’observaient que chez les patients SL. Par ailleurs, nous avons montré qu’elles étaient 3 fois plus fréquentes dans la muqueuse adjacente à la tumeur que dans la muqueuse distante. Nous avons identifié des MMR-DCF chez un patient «Lynch-like», ce qui est un argument diagnostique en faveur d’un authentique SL. Les MMR-DCF devraient donc être systématiquement recherchées dans la muqueuse adjacente dans ce contexte. Par ailleurs, un défaut de champ en MGMT (O6-methylguanine-DNA-methyltransferase, une enzyme impliquée dans la réparation de l’ADN) dans la muqueuse non néoplasique pourrait favoriser la cancérogénèse MSI, par un mécanisme de tolérance à la méthylation. En évaluant l’expression de la MGMT comparativement à celle des protéines MMR, nous avons constaté que les MMR-DCF étaient plus fréquemment identifiées en cas de perte d’expression de la MGMT (p=0.004), et préférentiellement en cas de défaut de champ en MGMT. L’inactivation de la MGMT constituerait donc un événement précurseur favorisant l’apparition de MMR-DCF chez les patients atteints de SL.Inactivation of MMR (MisMatch Repair) system drives microsatellite instable (MSI) carcinogenesis. MSI colorectal cancers (CRC) may occur either in a hereditary (Lynch syndrome, LS) or sporadic context. Recently, MMR-deficient crypt foci (MMR-DCF) were described in non-neoplastic intestinal mucosa of LS patients. These are morphologically normal crypts, which exhibit loss of a MMR protein, and may constitute a pre-neoplastic event in LS. In some cases of early onset MSI CRC, diagnosis of LS is uncertain because no germline mutation is identified; theses cases are considered as “Lynch-like”. We detected MMR-DCF only in LS-CRC, and the ratio of MMR-DCF was 3 times higher in adjacent mucosa than in distant mucosa. We identified MMR-DCF in one “Lynch-like” patients; this is an argument that favors LS in this patient and that suggests that screening for MMR-DCF should be systematically performed in adjacent mucosa in this context. Furthermore, this pathway of MSI carcinogenesis could be favored by an O6-methylguanine-DNA-methyltransferase (MGMT) field defect in the non-neoplastic colorectal mucosa, through a mechanism called “methylation tolerance”. We compared MGMT and MMR proteins expression in the same crypts in non-neoplastic mucosa of LS-CRC patients and we noted that MMR-DCF were more frequently identified in case of loss of MGMT expression (p=0.004), and especially in case of MGMT field defect. We pointed that the inactivation of MGMT may constitute an initiating step for the emergence of MMR-DCF in patients with LS

L'inactivation de l'O6-méthylguanine-DNA-méthyltransférase (MGMT) constitue un événement précurseur de la cancérogénèse MSI

Inactivation of MMR (MisMatch Repair) system drives microsatellite instable (MSI) carcinogenesis. MSI colorectal cancers (CRC) may occur either in a hereditary (Lynch syndrome, LS) or sporadic context. Recently, MMR-deficient crypt foci (MMR-DCF) were described in non-neoplastic intestinal mucosa of LS patients. These are morphologically normal crypts, which exhibit loss of a MMR protein, and may constitute a pre-neoplastic event in LS. In some cases of early onset MSI CRC, diagnosis of LS is uncertain because no germline mutation is identified; theses cases are considered as “Lynch-like”. We detected MMR-DCF only in LS-CRC, and the ratio of MMR-DCF was 3 times higher in adjacent mucosa than in distant mucosa. We identified MMR-DCF in one “Lynch-like” patients; this is an argument that favors LS in this patient and that suggests that screening for MMR-DCF should be systematically performed in adjacent mucosa in this context. Furthermore, this pathway of MSI carcinogenesis could be favored by an O6-methylguanine-DNA-methyltransferase (MGMT) field defect in the non-neoplastic colorectal mucosa, through a mechanism called “methylation tolerance”. We compared MGMT and MMR proteins expression in the same crypts in non-neoplastic mucosa of LS-CRC patients and we noted that MMR-DCF were more frequently identified in case of loss of MGMT expression (p=0.004), and especially in case of MGMT field defect. We pointed that the inactivation of MGMT may constitute an initiating step for the emergence of MMR-DCF in patients with LS.L’inactivation du système de réparation des mésappariements de l’ADN (MisMatch Repair, MMR) favorise un processus oncogénique d’instabilité des microsatellites du génome (MicroSatellite Instability, MSI). Les cancers colorectaux (CCR) MSI peuvent s’observer dans un contexte familial (syndrome de Lynch, SL) ou sporadique. Les cryptes MMR déficientes (MMR-Deficient Crypt Foci, MMR-DCF), lésions de la muqueuse non tumorale perdant l’expression d’une protéine MMR, pourraient constituer un événement prénéoplasique de la carcinogénèse colorectale MSI chez les patients SL. Dans certains CCR MSI, les cas «Lynch-like», le diagnostic de SL ne peut être posé avec certitude car aucune mutation germinale pathogénique MMR n’est identifiée, malgré une forte suspicion clinico-phénotypique. Nous avons confirmé que les MMR-DCF ne s’observaient que chez les patients SL. Par ailleurs, nous avons montré qu’elles étaient 3 fois plus fréquentes dans la muqueuse adjacente à la tumeur que dans la muqueuse distante. Nous avons identifié des MMR-DCF chez un patient «Lynch-like», ce qui est un argument diagnostique en faveur d’un authentique SL. Les MMR-DCF devraient donc être systématiquement recherchées dans la muqueuse adjacente dans ce contexte. Par ailleurs, un défaut de champ en MGMT (O6-methylguanine-DNA-methyltransferase, une enzyme impliquée dans la réparation de l’ADN) dans la muqueuse non néoplasique pourrait favoriser la cancérogénèse MSI, par un mécanisme de tolérance à la méthylation. En évaluant l’expression de la MGMT comparativement à celle des protéines MMR, nous avons constaté que les MMR-DCF étaient plus fréquemment identifiées en cas de perte d’expression de la MGMT (p=0.004), et préférentiellement en cas de défaut de champ en MGMT. L’inactivation de la MGMT constituerait donc un événement précurseur favorisant l’apparition de MMR-DCF chez les patients atteints de SL

Une courte antibiothérapie diminue la fréquence des complications infectieuses après duodenopancréatectomie céphalique sur bile contaminée

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Postoperative peritonitis without an underlying digestive fistula after complete cytoreductive surgery plus HIPEC

Background/Aim: 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. Patients and Methods: Between 1994 and 2012, 607 patients underwent CCRS plus HIPEC in our tertiary care center and were retrospectively analyzed. Results: 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%. Conclusions: 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

Perioperative chemotherapy in colorectal cancer with peritoneal metastases : A global propensity score matched study

Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM. Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed. Findings: Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy. Interpretation: Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting

Surgical management of soft tissue tumors of the abdominal wall: A retrospective study in a high‐volume sarcoma center

peer reviewed[en] BACKGROUND: The aim of the study is to evaluate functional and oncological outcomes of patients undergoing abdominal wall soft tissue tumors (AWSTT) surgery. METHODS: All consecutive patients that underwent surgery for malignant and intermediate AWSTT from 1999 to 2019 were retrospectively analyzed. RESULTS: Ninety-two patients were identified, 20 (22%) operated on for a desmoid tumor and 72 (78%) for a soft tissue sarcoma (STS). Fifty-two patients (57%) had in toto resection of the abdominal wall (from the skin to the peritoneum) and 9 (10%) required simultaneous visceral resection. The closure was direct in 28 patients (30%) and requiring a mesh, a flap or a combination of the two in respectively 42, 16, and 6 patients (47%, 17%, 6%). The postoperative complications rate was 26%. Thirteen patients (14%) developed an incisional hernia after a median delay of 27 months. After a median follow-up of 40 months, out of the 72 patients operated on for STS, 7 (10%) developed local recurrence and 11 (15%) distant recurrence. The median recurrence-free and overall survivals were 61 and 116, months respectively. CONCLUSIONS: Management of AWSTT requires extensive surgery but allows good local control with an acceptable rate of incisional hernia