Summary Objective A clear relationship between higher surgeon volume and improved outcomes has not been convincingly established in rectal cancer surgery. The aim of this study was to evaluate the impact of individual surgeon’s caseload and hospital volume on perioperative outcome. Methods We retrospectively analyzed 336 consecutive patients undergoing oncological resection for rectal cancer at two Viennese hospitals between 1 January 2015 and 31 December 2020. The effect of baseline characteristics as well as surgeons’ caseloads (low volume: 0–5 cases per year, high volume > 5 cases per year) on postoperative complication rates (Clavien-Dindo Classification groups of < 3 and ≥ 3) were evaluated. Results No differences in baseline characteristics were found between centers in terms of sex, smoking status, or comorbidities of patients. Interestingly, only 14.7% of surgeons met the criteria to be classified as high-volume surgeons, while accounting for 66.3% of all operations. There was a significant difference in outcomes depending on the treating center in univariate and multivariate binary logistic regression analysis (odds ratio (OR) = 2.403, p = 0.008). Open surgery was associated with lower complication rates than minimally invasive approaches in univariate analysis (OR = 0.417, p = 0.003, 95%CI = 0.232–0.739) but not multivariate analysis. This indicated that the center’s policy rather than surgeon volume or mode of surgery impact on postoperative outcomes. Conclusion Treating center standards impacted on outcome, while individual caseload of surgeons or mode of surgery did not independently affect complication rates in this analysis. The majority of rectal cancer resections are performed by a small number of surgeons in Viennese hospitals.

Abstract Background One of the hallmarks of Crohn’s disease (CD) is mesenteric thickening, accompanied by enlarged draining lymph nodes (LNs) in the affected areas. Descriptive studies imply that lymphatic architecture is altered in affected areas. Additionally, an altered IgA and IgG response towards commensal bacteria in CD patients compared to healthy controls has been described. Thus, we set out to investigate the B cell response in draining lymph nodes of patients with CD undergoing surgery. Methods We prospectively collected draining lymph nodes and serum samples in patients with Crohn’s disease during intestinal resections. LNs of affected and adjacent unaffected intestinal segments were processed for phenotyping by flowcytometry (n=18) and B cell receptor (BCR) sequencing (n=24). Histological analysis was performed to investigate size and number of germinal centers in affected and unaffected areas (n=10). Serum samples were collected from patients with CD undergoing surgery (n=18), and healthy individuals (n=16). The study was approved by the local ethics committee (EK #1480/2016) and all patients prospectively gave their written informed consent to participate in the study. Results Affected draining LNs showed a significantly increased fraction of CD45+CD19+ B cells (p=0.0055) compared to unaffected LNs. Fractions of double negative B cells (p=0.0394) and plasmablasts (p=0.0126) were significantly increased, and memory B cells significantly decreased (p=0.0127) in affected draining lymph nodes, respectively. Histological analysis revealed no difference in the numbers of germinal centers per high power field, but a significantly increased germinal center size (p<0.001). BCR sequencing demonstrated a reduction in IGHA (p<0.001) and IGHE (p=0.031), and a significant increase in IGHG1/2 (p<0.001) in affected LNs compared to unaffected LNs. Analysis of somatic hypermutation of BCRs and diversity analysis showed no significant increase in somatic hypermutation in IGHG1/2, and diversity analysis indicated significant diversity in specificity. Serum IgA of patients with CD recognized a significantly greater fraction of commensals in CD patients, and IgG binding towards commensals was almost universally detectable in CD patients but absent in healthy controls. Conclusion Our data indicate that a pathological IgG response in patients with severe disease is directed towards a broad set of antigens, most likely stemming from commensals. Additionally, expansion only at the site of inflammation may indicate a triggered immune response due to a leaky intestinal barrier. The relevance of pathological IgG antibodies on disease recurrence following surgery needs to be addressed in future studies.

Zusammenfassung Die Inzidenz von Morbus Crohn, einer chronisch-entzündlichen Darmerkrankung, steigt an. Obwohl die Therapiemöglichkeiten verbessert wurden, entwickelt ein Großteil der PatientInnen Komplikationen, die eine chirurgische Intervention benötigen. So können neben Stenosen auch Perforationen oder Fisteln entstehen, die eine dringliche chirurgische Darmresektion notwendig machen. Aufgrund des hohen Lebenszeitrisikos für die Notwendigkeit einer chirurgischen Therapie von Komplikationen, bedarf es einer optimalen Koordination von konservativer und operativer Therapie. Dies inkludiert sowohl Indikation zur Art der Chirurgie, als auch die postoperative Rezidivprophylaxe, sodass die Behandlung wegen der komplexen Interaktion in einem spezialisierten Zentrum erfolgen sollte, um den besten Operationszeitpunkt zu wählen. Um nach einer Darmresektion die Rekonvaleszenz zu beschleunigen und das Komplikationsrisiko zu minimieren, sind in den letzten Jahren einerseits die Laparoskopie als Standardzugang, andererseits spezielle chirurgische Anastomosen- und Resektionstechniken propagiert worden. Zusätzlich sollte in der Nachsorge die Einbindung der PatientInnen in ein gastroenterologisches Nachsorgeprogramm mit regelmäßigen, endoskopischen Untersuchungen erfolgen, um Rezidive zu erkennen und zu behandeln. Risikofaktoren für ein Frührezidiv nach Operationen beinhalten Rauchen, vorherige Operationen, das Fehlen von prophylaktischer medikamentöser Therapie, penetrierende/fistulierende Komplikationen bei Erstoperation, perianale Komplikationen, Granulome und myenterische Plexitis. In diesem Artikel fassen wir die gängigen Richtlinien sowie aktuelle Studien, die möglicherweise Einzug in die gängige Praxis finden, zusammen.

Nicotine addiction develops predominantly during human adolescence through smoking. Self-administration experiments in rodents verify this biological preponderance to adolescence, suggesting evolutionary-conserved and age-defined mechanisms which influence the susceptibility to nicotine addiction. The hippocampus, a brain region linked to drug-related memory storage, undergoes major morpho-functional restructuring during adolescence and is strongly affected by nicotine stimulation. However, the signaling mechanisms shaping the effects of nicotine in young vs. adult brains remain unclear. MicroRNAs (miRNAs) emerged recently as modulators of brain neuroplasticity, learning and memory, and addiction. Nevertheless, the age-dependent interplay between miRNAs regulation and hippocampal nicotinergic signaling remains poorly explored. We here combined biophysical and pharmacological methods to examine the impact of miRNA-132/212 gene-deletion (miRNA-132/212−/−) and nicotine stimulation on synaptic functions in adolescent and mature adult mice at two hippocampal synaptic circuits: the medial perforant pathway (MPP) to dentate yrus (DG) synapses (MPP-DG) and CA3 Schaffer collaterals to CA1 synapses (CA3–CA1). Basal synaptic transmission and short-term (paired-pulse-induced) synaptic plasticity was unaltered in adolescent and adult miRNA-132/212−/− mice hippocampi, compared with wild-type controls. However, nicotine stimulation promoted CA3–CA1 synaptic potentiation in mature adult (not adolescent) wild-type and suppressed MPP-DG synaptic potentiation in miRNA-132/212−/− mice. Altered levels of CREB, Phospho-CREB, and acetylcholinesterase (AChE) expression were further detected in adult miRNA-132/212−/− mice hippocampi. These observations propose miRNAs as age-sensitive bimodal regulators of hippocampal nicotinergic signaling and, given the relevance of the hippocampus for drug-related memory storage, encourage further research on the influence of miRNAs 132 and 212 in nicotine addiction in the young and the adult brain.

The incidence of Crohn’s disease, an inflammatory bowel disease, has increased in recent years. Despite a large new armamentarium of drugs, a significant fraction of patients with Crohn’s disease develop intestinal complications requiring surgical intervention. In addition to strictures, fistulas or perforations can require urgent or elective surgery and intestinal resection. Due to the high lifetime risk for complications, surgeries should be planned and conducted in specialized centres with adequate caseloads, as this also minimizes the risk of postoperative complications. In general, decisions to perform a surgical intervention should be made in an interdisciplinary setting. Laparoscopy has become the standard of care and is increasingly utilized for recurrent interventions. In addition, scientific literature has shown that special surgical anastomotic techniquesmay reduce clinical and endoscopic recurrence. Postoperatively, surveillance should be offered by specialized gastroenterologists and endoscopy should be performed regularly to identify early recurrence. While several of the perioperative factors can be optimized, independent risk factors for recurrence are smoking, prior surgery, lack of prophylactic immunosuppression, penetrating/fistulizing disease at the time of index surgery, perianal complications, and presence of granulomas and/or myenteric plexitis. In this article, we summarize current guidelines and highlight studies that may be of relevance for clinical practice in the future.

Cerebral ischemia and its sequelae, which include memory impairment, constitute a leading cause of disability worldwide. Micro-RNAs (miRNA) are evolutionarily conserved short-length/noncoding RNA molecules recently implicated in adaptive/maladaptive neuronal responses to ischemia. Previous research independently implicated the miRNA-132/212 cluster in cholinergic signaling and synaptic transmission, and in adaptive/protective mechanisms of neuronal responses to hypoxia. However, the putative role of miRNA-132/212 in the response of synaptic transmission to ischemia remained unexplored. Using hippocampal slices from female miRNA-132/212 double-knockout mice in an established electrophysiological model of ischemia, we here describe that miRNA-132/212 gene-deletion aggravated the deleterious effect of repeated oxygen-glucose deprivation insults on synaptic transmission in the dentate gyrus, a brain region crucial for learning and memory functions. We also examined the effect of miRNA-132/212 gene-deletion on the expression of key mediators in cholinergic signaling that are implicated in both adaptive responses to ischemia and hippocampal neural signaling. miRNA-132/212 gene-deletion significantly altered hippocampal AChE and mAChR-M1, but not α7-nAChR or MeCP2 expression. The effects of miRNA-132/212 gene-deletion on hippocampal synaptic transmission and levels of cholinergic-signaling elements suggest the existence of a miRNA-132/212-dependent adaptive mechanism safeguarding the functional integrity of synaptic functions in the acute phase of cerebral ischemia.