Secretory immunoglobulin A (SIgA) can travel to and from the lumen and transport antigen to subepithelial cells. However, IgM can also multimerize into functional secretory component-bound ...immunoglobulin. While it is already known that both SIgA and SIgM undergo transcytosis to be secreted at the mucosal surface, only SIgA has been shown to perform retrotranscytosis through microfold cells (M cells) of the Peyer’s patch. Here, we investigate whether SIgM could also be taken up by M cells via retrotranscytosis. This transport involves FcμR binding at the apical membrane of M cells. We then demonstrate that SIgM can be exploited by SIgM-p24 (HIV-capsid protein) complexes during immunization in the nasal- or gut-associated lymphoid tissue (NALT or GALT), conferring efficient immune responses against p24. Our data demonstrate a mucosal function of SIgM, which could play a role in the regulation of mucosal immunity.
Display omitted
•SIgM is taken up by TOSO+ M cells of the murine GALT and the NALT•SIgM is retro-transported toward DC-SIGN+ DCs from lymphoid tissues•SIgM-based complexes result in mucosal and systemic antigen-specific antibody responses
Rochereau et al. investigate the transport of SIgM across the murine nasal and gut mucosa. They provide evidence that IgM is taken up by mucosal M cells and then retro-transported toward cells in lymphoid tissues. This function of SIgM could play an important role in the regulation of mucosal immunity.
The optimal in-hospital observation periods associated with minimal risks of complications and unplanned readmission after laparoscopic liver resection are unknown. The purpose of this study was to ...assess changes in the risks of postoperative complications over time.
Surgical complexity of laparoscopic liver resection was stratified into grades I (low complexity), II (intermediate), and III (high) using our 3-level complexity classification. The cumulative incidence rate and conditional probability of postoperative complication and risk factors for complication Clavien-Dindo grade ≥II (defined as treatment-requiring complications) were assessed.
The cumulative incidence of treatment-requiring complications was higher in patients undergoing grade III resection than in patients undergoing grade I resection (32.3% vs 10.4%, P < .001) and grade II resection (32.3% vs 20.7%, P = .019). The conditional probability of postoperative complication stratified by our complexity classification decreased over time and was <10% for patients undergoing grade I resection on postoperative day 1, grade II resection on postoperative day 4, and grade III resection on postoperative day 10.
The conditional cumulative incidence of treatment-requiring complications for patients undergoing laparoscopic liver resection is well stratified based on the 3-level complexity classification. Conditional complication risk analysis stratified by the 3 complexity grades may be useful for optimizing in-hospital observation after laparoscopic liver resection.
Introduction
Surgeons often remain reluctant to consider laparoscopic approach in multiple liver tumors. This study assessed feasibility and short-term results of patients who had more than 3 ...simultaneous laparoscopic liver resections (LLR).
Methods
All consecutive patients who underwent LLR for primary or secondary malignancies between 2009 and 2019 were analyzed. After exclusion of major LLR, patients were divided into three groups: less than three (Group A), between three and five (Group B), and more than five resections (Group C) in the same procedure. Intraoperative details, postoperative outcomes, and textbook outcome (TO) were compared in the 3 groups.
Results
During study period, 463 patients underwent minor LLR. Among them, 412 (88.9%) had less than 3 resections, 38 (8.2%) between 3 and 5 resections, and 13 (2.8%) more than 5 resections. Despite a difficulty score according to IMM classification comparable in the 3 groups (with high difficulty grade 3 procedures of 16.5% vs. 15.7% vs. 23.1% in Group A, B, and C, respectively,
p
= 0.124), mean operative time was significantly longer in Group C (
p
= 0.039). Blood loss amount (
p
= 0.396) and conversion rate (
p
= 0.888) were similar in the 3 groups. Rate of R1 margins was not significantly different between groups (
p
= 0.078). Achievement of TO was not different between groups (
p
= 0.741). In multivariate analysis, non-achievement of TO was associated with difficulty according to IMM classification (OR = 2.29 (1.33–3.98)).
Conclusion
Since intra- and post-operative outcomes and quality of resection are comparable, multiple liver resections should not preclude the laparoscopic approach.
Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse‐transcytosis, the apical‐to‐basal transport of IgA2 immune ...complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan–glycan interaction. Here, we asked whether IgA1 and IgA2‐microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC‐purified IgA, we show that reverse‐transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA‐bound microbiota in CD and UC showed distinct IgA1‐ and IgA2‐associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti‐glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.
Synopsis
IBD (both CD and UC) is characterized by dysbiosis and altered immune pathways that lead to and sustain prolonged inflammation in the gut. As IgA are the main drivers of commensal selection in the healthy gut, this study aimed at assessing subclass‐related structure and functions of IgA in both CD and UC.
Evidence of a chain of subclass‐dependent functional disparities between CD and UC IgAs affecting antibody glycosylation, transport across epithelia, and affinity, which may interfere in optimal commensal selection to promote dysbiosis
While only IgA2 could undergo RT in non‐IBD, IgA1 in CD had the ability to do so and neither IgA1 nor IgA2 were able to in UC.
Despite predominant dual IgA1 and IgA2 binding on stool microbiota, CD associates with enriched commensal binding in the IgA1+ fraction, and UC with a marked reduction in IgA overall reactivity
IBD (both CD and UC) is characterized by dysbiosis and altered immune pathways that lead to and sustain prolonged inflammation in the gut. As IgA are the main drivers of commensal selection in the healthy gut, this study aimed at assessing subclass‐related structure and functions of IgA in both CD and UC.
Background
Even though minimally invasive esophageal surgery (MIE) is spreading, questions remain regarding its oncological outcomes. The aim of this study was to assess the quality of oncological ...resection criteria in MIE.
Methods
All patients undergoing a two-way Ivor Lewis esophagectomy for esophageal or junctional cancer between 2010 and 2020 in a single tertiary upper gastrointestinal surgery ward were analyzed retrospectively. The following oncological criteria were analyzed: lymph node (LN) harvest and location, positive lymph node rate, margins, and R0 rates. They were compared between the MIE group (thoracoscopy + laparoscopy) and the hybrid group (H/O, thoracotomy + laparoscopy).
Results
Among the 240 patients included, 34 (14%) had MIE and 206 a hybrid esophagectomy. Main surgical indication was lower thoracic adenocarcinoma and the rate of neoadjuvant treatments administered (chemotherapy or chemoradiotherapy) was comparable between both groups (
p
= 1.0). LN harvest was significantly higher in the MIE group (31 ± 9 vs. 28 ± 9,
p
= 0.04) as well as thoracic LN harvest (14 ± 7 vs. 11 ± 5,
p
= 0.002). When analyzing patients according to T stage and response to neoadjuvant treatments, patients with T1 and T2 tumors and patients with a poor pathological response (TRG3, 4, 5) had a significantly higher LN harvest when undergoing a minimally invasive approach (
p
= 0.021 and
p
= 0.01, respectively). Positive LN rates (1.26 ± 3.63 in the MIE group vs. 1.60 ± 2.84 in the H/O group,
p
= 0.061), R0 rates (97% vs. 98.5%,
p
= 0.46) as well as proximal (
p
= 0.083), distal (
p
= 0.063), and lateral (
p
= 0.15) margins were comparable between both approaches.
Conclusion
MIE seems oncologically safe and may even be better than the open approach in terms of LN harvest especially in patients with T1 and T2 tumors and in poor responders.
A significant gap in pancreatic ductal adenocarcinoma (PDAC) patient's care is the lack of molecular parameters characterizing tumours and allowing a personalized treatment.
Patient-derived ...xenografts (PDX) were obtained from 76 consecutive PDAC and classified according to their histology into five groups. A PDAC molecular gradient (PAMG) was constructed from PDX transcriptomes recapitulating the five histological groups along a continuous gradient. The prognostic and predictive value for PMAG was evaluated in: i/ two independent series (n = 598) of resected tumours; ii/ 60 advanced tumours obtained by diagnostic EUS-guided biopsy needle flushing and iii/ on 28 biopsies from mFOLFIRINOX treated metastatic tumours.
A unique transcriptomic signature (PAGM) was generated with significant and independent prognostic value. PAMG significantly improves the characterization of PDAC heterogeneity compared to non-overlapping classifications as validated in 4 independent series of tumours (e.g. 308 consecutive resected PDAC, uHR=0.321 95% CI 0.207–0.5 and 60 locally-advanced or metastatic PDAC, uHR=0.308 95% CI 0.113–0.836). The PAMG signature is also associated with progression under mFOLFIRINOX treatment (Pearson correlation to tumour response: -0.67, p-value < 0.001).
PAMG unify all PDAC pre-existing classifications inducing a shift in the actual paradigm of binary classifications towards a better characterization in a gradient.
Project funding was provided by INCa (Grants number 2018–078 and 2018–079, BACAP BCB INCa_6294), Canceropole PACA, DGOS (labellisation SIRIC), Amidex Foundation, Fondation de France, INSERM and Ligue Contre le Cancer.
Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic ...testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM.
To validate the Institut Mutualiste Montsouris classification as a difficulty scoring system applicable to laparoscopic repeat liver resections and identify risk-factors of unexpected difficulty.
...From a prospectively collected database between 2000 and 2019, patients undergoing laparoscopic repeat liver resections were classified according to the Institut Mutualiste Montsouris classification. Doubly robust estimators (weighted regressions) were used to assess the effect of factors on intra- and postoperative outcomes and allowed for strong adjustment on age, body mass index, American Society of Anesthesiologists, carcinoembryonic antigen, number, and size of lesions. Unexpected difficulty was defined as a composite indicator which included substantial blood loss and/or substantial operative time and/or conversion.
Of 205 laparoscopic repeat liver resections patients, 87, 25, and 93 procedures were classified as grade 1, 2, and 3 laparoscopic repeat liver resections, respectively. After doubly robust adjustment, the IMM classification was associated with blood loss (Cohen f2 0.12; P = 0.001), operative time (Cohen f2 0.07; P = .001), and length of stay (Cohen f2 0.13; P = .001), as well as with the risk of both minor and severe complications (odd ratio = 2.94; 95% confidence interval: 2.06–4.20) and the chances of achieving textbook outcome (relative risk = 0.57; 95% confidence interval: 0.41–0.81). Independently from the Institut Mutualiste Montsouris classification, a first major hepatectomy (relative risk = 1.15, 95% confidence interval: 1.03–1.29) as well as sinusoidal obstruction syndrome (relative risk = 1.24, 95% confidence interval: 1.09–1.41) were independent risk factors of unexpected difficulty. A first major resection was associated with decreased chances of textbook outcome (relative risk = 0.53; 95% confidence interval: 0.33–0.85).
The Institut Mutualiste Montsouris classification is a valuable difficulty scoring system for laparoscopic repeat liver resections procedures, while previous major resection and presence of sinusoidal obstruction syndrome are likely to jeopardize the outcomes.
Prosthetic joint infections (PJI) are responsible for significant morbidity and mortality and their number continues to rise. Their management remains complex, especially the microbiological ...diagnosis. Besides ‘homemade’ tests developed by several teams, new molecular biology methods are now available with different analytical performance and usability.
We studied the performances of one of these tests: ITI® multiplex PCR (mPCR) by the Curetis® company and compared it to either ‘optimized’ culture or 16S rRNA PCR. We performed a retrospective multicentre study to assess the contributions of mPCR in the diagnosis of PJI. We randomly selected 484 intraoperative specimens among 1252 of various types (biopsy, bone, tissue around the prosthesis, synovial fluid) from 251 patients in seven different hospitals. Each sample was treated according to the recommendations of the manufacturer.
In all, 154 out of 164 (93.9%) samples negative in culture were negative with the mPCR. Among the 276 positive samples in culture, 251 (90.9%) were monomicrobial, of which 119 (47.4%) were positive with the mPCR, and 25 (9.1%) were polymicrobial, of which 12 (48%) were positive with the mPCR. The concordance rate of mPCR with culture was 58.1% (53.6%–62.7%) and the concordance rate with 16S rRNA PCR was 70.1% (65.5%–74.6%).
This new standardized molecular test showed a lack of detection when the bacterial inoculum was low (number of positive media per sample and number of colonies per media) but can be useful when patients have received antibiotic therapy previously.
The development of laparoscopic liver resection has led to the hypothesis that intraoperative blood loss may be a key indicator of surgical care quality. This study assessed short- and long-term ...results of patients according to three levels of intraoperative blood loss during laparoscopic liver resection for colorectal liver metastasis.
All patients who underwent laparoscopic liver resection for colorectal liver metastasis between 2000 and 2018 were included. Difficulty of laparoscopic liver resection was defined according to the Institut Mutualiste Montsouris classification. Three levels of the extent of intraoperative blood loss were defined: massive (≥1,000 mL), substantial (≥75th percentile of intraoperative blood loss within each grade of difficulty), and normal intraoperative blood loss.
During study period, 317 patients underwent laparoscopic liver resection for colorectal liver metastasis. Among them, 213 (67.2%), 80 (25.2%), and 24 (7.6%) patients had normal, substantial, and massive intraoperative blood loss, respectively. Twenty-six patients (8.2%) required transfusion. Massive intraoperative blood loss came from a major hepatic vein in 54% of cases and were managed by laparoscopy in 83% of the cases. Laparoscopic liver resection difficulty grade (odds ratio = 3.15; P = .053) and number of colorectal liver metastasis (odds ratio = 1.24; P = .020) were independently associated with massive intraoperative blood loss. Risks factors for substantial intraoperative blood loss were bi-lobar colorectal liver metastasis (odds ratio = 3.12; P = .033) and sinusoidal obstruction syndrome (odds ratio = 3.27; P = .004). The level of intraoperative blood loss was not associated with severe complications nor overall and disease-free survival. Requirement of transfusion was associated with severe complications (odds ratio = 7.27; P = .002) and decreased 1-, 3-, and 5-year overall survival (87%, 68%, and 61% vs 95%, 88%, and 79%; P = .042).
The extent of intraoperative blood loss did not affect short- and long-term results of laparoscopic liver resection for colorectal liver metastasis. Massive intraoperative blood loss was often incidental and, 83% of the time, manageable by laparoscopy. Rather than intraoperative blood loss, transfusion is a better relevant indicator of laparoscopic liver resection surgical quality.
PDF
