[Abdominal surgery: what's new in 2023]. / Chirurgie viscérale: ce qui a changé en 2023.

In 2023, robotic surgery has witnessed an expansion in the number of surgical procedures and in the number of platforms on the market. We illustrate the phenomenon, by exploring parietal, œso-gastric and liver robotic surgery. Surgical innovation aligns with advancements in oncology. Immunotherapy now enables "watch and wait" strategies for patients with colorectal cancer, and decreases recurrence rate and improves survival after liver surgery for hepatocellular carcinoma and œso-gastric surgery. The multidisciplinary field of obesity management has seen the development of new medications, diversifying the treatment options, while surgery continues to deliver the best weight-loss outcomes.

En 2023, la chirurgie robotique a poursuivi son expansion avec une augmentation du nombre d'interventions et la mise sur le marché de nouvelles plateformes. Ce phénomène est illustré dans cet article par la description des chirurgies robotique pariétale, œsogastrique et hépatique. L'innovation en chirurgie accompagne aussi celle de l'oncologie. L'immunothérapie permet maintenant une stratégie « watch and wait ¼ chez les patients avec un cancer colorectal, diminue le risque de récidive et améliore la survie après chirurgie hépatique pour un carcinome hépatocellulaire et chirurgie œsogastrique. Le domaine multidisciplinaire de la prise en charge de l'obésité a aussi vu l'arrivée de nouveaux traitements médicamenteux, qui viennent diversifier les options thérapeutiques, où la chirurgie continue d'apporter les meilleurs résultats en termes de perte de poids.

Improving care pathways for people living with rare bone diseases (RBDs): outcomes from the first RBD Summit.

INTRODUCTION: Rare bone diseases (RBDs) are a heterogenous group of disorders that are poorly understood and challenging to treat. This creates a plethora of unmet needs for people with RBDs as well as their families and care providers, including diagnostic delays, limited access to expert care, and a lack of specialized treatments. The RBD Summit, which took place across 2 days in November 2021, was a virtual meeting of 65 RBD experts from clinical, academic, and patient communities as well as the pharmaceutical industry. The first meeting of its kind, the RBD Summit aimed to facilitate dialog and information exchange between delegates to advance knowledge and awareness of RBDs and improve patient outcomes. METHODS: Key challenges were discussed, and actions for overcoming them were proposed, including how obstacles to diagnosis can be overcome by (a) improving awareness of RBDs, (b) the implementation of a person-centered care pathway, and (c) how to narrow the communication gap between patients and healthcare professionals. RESULTS: Agreed actions were categorized as short term and long term, and priorities determined. CONCLUSION: In this position paper, we provide an overview of key discussions from the RBD Summit, summarize the subsequent action plan, and discuss the next steps in this continued collaboration.

Current Surgical Strategies for the Treatment of Rectal Adenocarcinoma and the Risk of Local Recurrence.

BACKGROUND: Despite new medical and surgical strategies, 5-year local recurrence of rectal adenocarcinoma was reported in up to 25% of cases. Therefore, we aimed to review surgical strategies for the prevention of local recurrences in rectal cancer. SUMMARY: After implementation of the total mesorectal excision (TME), surgical resection of rectal adenocarcinoma with anterior resection or abdominoperineal excision (APE) allowed decrease in local recurrence (3% at 5 years). More recently, extralevator APE was described as an alternative to APE, decreasing specimen perforation and recurrence rate. Moreover, technique modifications were developed to optimize rectal resection, such as the laparoscopic or robotic approach, and transanal TME. However, the technical advantages conferred by these techniques did not translate into a decreased recurrence rate. Lateral lymph node dissection is another technique, which aimed at improving the long-term outcomes; nevertheless, there is currently no evidence to recommend its routine use. Strategies to preserve the rectum are also emerging, such as local excision, and may be beneficial for subgroups of patients. Key Messages: Rectal cancer management requires a multidisciplinary approach, and surgical strategy should be tailored to patient factors: general health, previous perineal intervention, anatomy, preference, and tumor characteristics such as stage and localization.

Wandering Spleen Volvulus: A Case Report and Literature Review of This Diagnostic Challenge.

BACKGROUND Wandering spleen is a rare condition in which the spleen lacks the usual peritoneal attachments, resulting in increased intra-abdominal mobility. Complications can occur due to the torsion of the splenic vascular pedicle, resulting in symptoms ranging from an incidental finding to an acute abdomen as a result of an ischemic necrosis of the spleen. CASE REPORT We present the case of a 25-year-old female patient who presented with a recurring abdominal pain associated with serum lipase and C-reactive protein elevation. The computed tomography scan revealed torsion of the splenic pedicle and hypoperfusion of the spleen. A surgical exploration was performed and a wandering spleen was diagnosed perioperatively. It was characterized by the lack of peritoneal ligaments, thus resulting in a splenic volvulus. A splenectomy was carried out due to the definite ischemic necrosis of the spleen. CONCLUSIONS The diagnosis of this rare condition can be very challenging since it can be presented with a vast variety of symptoms, mimicking other abdominal pathologies. The intermittent nature of an ultimate splenic torsion can add to the diagnostic challenge. Medical literature concerning the wandering spleen and knowledge about this pathology originates mainly from individual case reports. Despite the evolving diagnostic modalities available, this rare and ambiguous disorder remains misdiagnosed, and a high index of suspicion is needed for the appropriate diagnosis to be established.

Human CD56dimCD16dim Cells As an Individualized Natural Killer Cell Subset.

Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of the relative expression of the adhesion molecule CD56 and the activating receptor CD16. Whereas blood CD56brightCD16dim/- NK cells are classically viewed as immature precursors and cytokine producers, the larger CD56dimCD16bright subset is considered as the most cytotoxic one. In peripheral blood of healthy donors, we noticed the existence of a population of CD56dimCD16dim NK cells that was frequently higher in number than the CD56bright subsets and even expanded in occasional control donors but also in transporter associated with antigen processing-deficient patients, two familial hemophagocytic lymphohistiocytosis type II patients, and several common variable immunodeficiency patients. This population was detected but globally reduced in a longitudinal cohort of 18 HIV-1-infected individuals. Phenotypically, the new subset contained a high percentage of relatively immature cells, as reflected by a significantly stronger representation of NKG2A+ and CD57- cells compared to their CD56dimCD16bright counterparts. The phenotype of the CD56dimCD16dim population was differentially affected by HIV-1 infection as compared to the other NK cell subsets and only partly restored to normal by antiretroviral therapy. From the functional point of view, sorted CD56dimCD16dim cells degranulated more than CD56dimCD16bright cells but less than CD56dimCD16- NK cells. The population was also identified in various organs of immunodeficient mice with a human immune system ("humanized" mice) reconstituted from human cord blood stem cells. In conclusion, the CD56dimCD16dim NK cell subpopulation displays distinct phenotypic and functional features. It remains to be clarified if these cells are the immediate precursors of the CD56dimCD16bright subset or placed somewhere else in the NK cell differentiation and maturation pathway.

Polyclonal Expansion of NKG2C(+) NK Cells in TAP-Deficient Patients.

Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C(+) NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C(+) NK cell expansions. We demonstrate the expansion of NKG2C(+) NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C(+) NK cell populations in TAP-deficient patients display a polyclonal KIR profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR repertoire of expanding NKG2C(+) NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C(+) NK cell expansions to occur. The emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to antiviral immunity and potentially explain these patients' low incidence of severe viral infections.

NK cell killer Ig-like receptor repertoire acquisition and maturation are strongly modulated by HLA class I molecules.

The interaction between clonally distributed inhibitory receptors and their activating counterparts on NK cells and HLA class I molecules defines NK cell functions, but the role of HLA class I ligands in the acquisition of their receptors during NK development is still unclear. Although some studies demonstrated that HLA-C affects the expression of killer Ig-like receptors (KIR), other studies showed that NK cells acquire their KIR repertoire in a stochastic manner. Only when infected with human CMV is an expansion of self-specific KIR(+) NKG2C(+) NK cells detected. To gain more insight into this question, we compared the coexpression of different KIR molecules, NKG2A, CD8, and CD57, on NK cells in healthy donors and seven patients with deficient HLA class I expression due to mutations in one of the TAP genes. Our results show a correlation between the presence/absence of HLA class I molecules and the coexpression of their receptors. In an HLA class I low-expression context, an increase in KIR molecules' coexpression is detected on the NKG2A(+) CD8(+) subset. In functional assays, hyporesponsiveness was observed for TAP-deficient NK cells derived from four patients. In contrast, NK cells from patient five were functional, whereas CD107a(+) and IFN-γ(+) CD56(dim) NK cells presented a different pattern of HLA class I receptors compared with healthy donors. Taken together, our results provide strong evidence for the role of HLA class I molecules in NK cell maturation and KIR repertoire acquisition.

8-Modified-2'-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription.

The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix αH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2'-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2'-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.