Gut CD4
T cells are incompletely restored in most HIV-1-infected individuals on antiretroviral therapy, notably Th17 cells, a key subset in mucosal homeostasis. By contrast, gut Th22 cells are ...usually restored at normal frequencies. Th22 cells display a CCR6
CCR10
phenotype and could thus respond to CCL20- and CCL28-mediated chemotaxis, while Th17 cells, which express CCR6 but not CCR10, depend on CCL20. Herein, we found that CCL28 is normally expressed by duodenal enterocytes of treated HIV-1-infected individuals, while CCL20 expression is blunted. Ex vivo, we showed that Th22 cells contribute to the reduction of CCL20 production by enterocytes through an IL-22- and IL-18-dependent mechanism. Th22 cells preferentially migrate via CCL20- rather than CCL28-mediated chemotaxis when both chemokines are available in the microenvironment. However, when the CCL20/CCL28 ratio drops, as in treated HIV-1-infected individuals, Th22 cells can migrate via the CCR10-CCL28 axis, as an alternative to CCR6-CCL20. This could explain the better reconstitution of gut Th22 compared with Th17 cells on antiretroviral therapy. Lastly, we assessed the relationships between the frequencies of gut Th17 and Th22 cells and inflammatory markers related to microbial translocation, and showed that Th22 cells do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals.
Abstract Background About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims ...of the present study was to evaluate the “step up” approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. Methods In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). Results Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. Conclusions Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.
Alpha-fetoprotein(AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma(HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, ...it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/m L could be an exclusion criterion, whereas values of < 15 ng/m L indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.
Only 2 large (more than 100 patients) prospective trials comparing pancreatogastrostomy (PG) with pancreatojejunostomy (PJ) after pancreatoduodenectomy (PD) have been reported until now. One ...nonrandomized study showed that there were less pancreatic and digestive tract fistula with PG, whereas the other, a randomized trial from a single high-volume center, found no significant differences between the two techniques.
Single blind, controlled randomized, multicenter trial. The main endpoint was intra-abdominal complications (IACs).
Of 149 randomized patients, 81 underwent PG and 68 PJ. No significant difference was found between the two groups concerning pre- or intraoperative patient characteristics. The rate of patients with one or more IACs was 34% in each group. Twenty-seven patients sustained a pancreatoenteric fistula (18%), 13 in PG (16%; 95% confidence interval CI 8–24%) and 14 in PJ (20%; 95% CI 10.5–29.5%). No statistically significant difference was found between the 2 groups concerning the mortality rate (11% overall), the rate of reoperations and/or postoperative interventional radiology drainages (23%), or the length of hospital stay (median 20.5 days). Univariate analysis found the following risk factors: (1) age ≥70 years old, (2) extrapancreatic disease, (3) normal consistency of pancreas, (4) diameter of main pancreatic duct <3 mm, (5) duration of operation >6 hours, and (6) a center effect. Significantly more IAC, pancreatoenteric fistula, and deaths occurred in one center (that included the most patients) (
P = .05), but there were significantly more high-risk patients in this center (normal pancreas consistency, extrapancreatic pathology, small pancreatic duct, higher transfusion requirements, and duration of operation >6 hours) compared with the other centers. In multivariate analysis, the center effect disappeared. Independent risk factors included duration of operation >6 hours for IAC and for pancreatoenteric fistula (
P = .01), extrapancreatic disease for pancreatoenteric fistulas (
P < .04), and age ≥70 years for mortality (
P < .02).
The type of pancreatoenteric anastomosis (PJ or PG) after PD does not significantly influence the rate of patients with one or more IAC and/or pancreatic fistula or the severity of complications.
Studies of risk factors after pancreatoduodenectomy are few: some concern restricted populations and others are based on administrative data.
Multicenter clinical data were collected for 300 patients ...undergoing pancreatoduodenectomy to determine (by univariate and multivariate analysis) preoperative and intraoperative risk factors for mortality and intra-abdominal complications (IACs), including pancreatic fistula. Fourteen factors including the center and volume effect were analyzed.
In univariate analysis, mortality was increased with age 70 years or more, extended resection(s), and volume and center effects. IACs occurred more often with main pancreatic duct diameter of 3 mm or less, normal parenchyma texture, extended resection(s), and the center effect. Pancreatic fistula was more frequent with main pancreatic duct diameter of 3 mm or less, normal parenchyma texture, and the center effect. In multivariate analysis, independent risk factor(s) for mortality were age greater than 70 years (odds ratio OR, 3; 95% confidence interval CI, 1.3-8) and extended resection (OR, 5; 95% CI, 1.2-22), risk factors for IACs were extended resection (OR, 5; 95% CI, 1.2-22) and main pancreatic duct diameter of 3 mm or less (OR, 2; 95% CI, 1.1-3), and the risk factor for pancreatic fistula was main pancreatic duct diameter of 3 mm or less (OR, 2.5; 95% CI, 1.2-4.6).
Age more than 70 years, extended resections, and main pancreatic duct diameter less than 3 mm are independent risk factors that should be considered in indications for and techniques of pancreatoduodenectomy.
Down‐regulation of detoxification genes, notably cytochrome P450 (CYPs), in primary hepatocyte cultures is a long‐standing and major concern. We evaluated the influence of medium flow in this model. ...Hepatocytes isolated from 12 different liver donors were cultured either in a multichamber modular bioreactor (MCmB, flow rate 250–500 μL/min) or under standard/static conditions, and the expression of 32 genes, enzyme activities and biological parameters were measured 7–21 days later. mRNA expression of genes involved in xenobiotic/drug metabolism and transport, including CYP1A1, 1A2, 2B6, 2C9, 3A4 (and activities for some of them), UDP‐glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B7, glutathione S‐transferase (GSTα), and multidrug resistance protein 1 (MDR1) and MRP2, were specifically up‐regulated by medium flow as compared with static controls in all cultures tested. In 2‐week‐old cultures, expression of detoxification genes reached levels close to or higher than those measured in freshly isolated hepatocytes. In contrast, CYP2D6 and most of other tested genes were not affected by medium flow. We conclude that medium flow specifically interferes with, and up‐regulates, the activity of xenosensors and/or the expression of detoxification genes in primary human hepatocytes. Down‐regulation of detoxification genes in conventional (static) cultures is therefore partly a consequence of the absence of medium circulation.
The localization of endometriotic disease in the hepatic pedicle has never been reported to date. We report the first case of a 67‐year‐old postmenopausal patient having presented an endometriotic ...lesion in the hepatic pedicle. A surgical biopsy was needed to confirm the diagnosis after a first radiologic biopsy that concluded the presence of a mucinous cystic tumor with low‐grade dysplasia. Medical treatment with aromatase inhibitors was carried out because of the inextirpable nature of the lesion. The diagnosis and therapeutic management of this rarely occurring lesion of atypical localization in a postmenopausal patient is presented here. A review of the literature on this localization could have led to a damaging surgical treatment due to the different diagnoses suggested. Management of endometriosis relies on a multidisciplinary approach that each practitioner must know how to broach with patients of all ages.
The aim of our study was to perform a 10-year imaging and clinical prospective follow-up of patients with nonoperated branch duct (BD) intraductal papillary mucinous neoplasms (IPMNs) of the ...pancreas.
Forty-nine patients with BD-IPMN who displayed a low probability for malignancy were followed up including a clinical component and a series of imaging techniques such as computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography.
After a mean follow-up period of 77 months, 77.5% of patients remained free of symptoms. An increase in the size and number of BD cysts without mural nodules and with no significant increase of main duct size occurred in 18 patients at an average interval of 47 months. Five patients were operated on owing to recurrent pancreatitis and/or an increase in the size of either cysts or the main duct (mean time delay after diagnosis: 20 months). Pathologically, they were diagnosed as benign adenoma (n = 1) or borderline (n = 4).
Our long-term clinical and imaging follow-up indicated that none of the patients with BD-IPMNs developed malignancy. Therefore, BD-IPMNs with no signs of malignancy should be managed conservatively. We propose that following a 2-year patient follow-up, biannual imaging follow-ups could be sufficient.
To compare patients hospitalised in the intensive care unit (ICU) after surgery for community-acquired intra-abdominal infection (CA-IAI) and hospital-acquired intra-abdominal infection (HA-IAI) in ...terms of mortality, severity and complications.
Retrospective study including all patients admitted to 2 ICUs within 48 h of undergoing surgery for peritonitis.
Two hundred twenty-six patients were enrolled during the study period. Patients with CA-IAI had an increased 28-day mortality rate compared to those with HA-IAI (30% vs 15%, respectively (p = 0.009)). At 90 days, the mortality rates were 36.7 and 37.5% in the CA-IAI group and HA-IAI group, respectively, with a similar APACHE II score on admission (median: 21 15-25 vs. 21 15-24 respectively, p = 0.63). The patients with HA-IAI had prolonged ICU and hospital stays (median: 17 7-36 vs. 63-12 days, p < 0.001 and 41 24-66 vs. 17 7-32 days, p = 0.001), and experienced more complications (reoperation and reintubation) than those with CA-IAI.
CA-IAI group had higher 28-day mortality rate than HA-IAI group. Mortality was similar at 90 days but those with HA-IAI had a prolonged ICU and hospital stay. In addition, they developed more complications.
Background
The aim of this study was to estimate the survival rates and define risk factors for tumor recurrence after resection surgery for single hepatocellular carcinomas (HCCs) ≤5 cm (on ...preoperative imaging) that developed on compensated cirrhosis.
Methods
A retrospective review studied patients treated by surgical resection. Overall survival (OS), disease-free survival (DFS), recurrence rates, and risk factors were studied for all patients.
Results
A total of 49 patients were treated by resection. The 5-year OS and DFS rates were 52 and 41%, respectively, after 2000. Three independent risk factors were found for OS and DFS: macroscopic vascular invasion, satellite nodules, R1 resection. In the absence of these three factors, the 5-year OS was 59%. Recurrence rates were 63%. Delayed recurrence was significantly related to the 5-year OS. One factor was correlated with early recurrence: the presence of satellite nodules; and one factor was correlated with late recurrence: hepatitis C virus infection.
Conclusions
R0 resection for HCC on compensated cirrhosis may offer good long-term survival in the absence of satellites nodules and macrovascular invasion. Thus, a “first approach” resection is proposed with the possibility of “salvage transplantation.” In other cases, resection may be a bridge to transplantation (“transplantation de principe”).
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