Abdominal vagus nerve stimulation as a new therapeutic approach to prevent postoperative ileus.

BACKGROUND: Electrical stimulation of the cervical vagus nerve (VNS) prevents postoperative ileus (POI) in mice. As this approach requires an additional cervical procedure, we explored the possibility of peroperative abdominal VNS in mice and human. METHODS: The effect of cervical and abdominal VNS was studied in a murine model of POI and lipopolysaccharide (LPS)-induced sepsis. Postoperative ileus was quantified by assessment of intestinal transit of fluorescent dextran expressed as geometric center (GC). Next, the effect of cervical and abdominal VNS on heart rate was determined in eight Landrace pigs to select the optimal electrode for VNS in human. Finally, the effect of sham or abdominal VNS on LPS-induced cytokine production of whole blood was studied in patients undergoing colorectal surgery. KEY RESULTS: Similar to cervical VNS, abdominal VNS significantly decreased LPS-induced serum tumor necrosis factor-α (TNFα) levels (abdominal VNS: 366±33 pg/mL vs sham: 822±105 pg/mL; P<.01). In line, in a murine model of POI, abdominal VNS significantly improved intestinal transit (GC: sham 5.1±0.2 vs abdominal VNS: 7.8±0.6; P<.01) and reduced intestinal inflammation (abdominal VNS: 35±7 vs sham: 80±8 myeloperoxidase positive cells/field; P<.05). In pigs, heart rate was reduced by cervical VNS but not by abdominal VNS. In humans, abdominal VNS significantly reduced LPS-induced IL8 and IL6 production by whole blood. CONCLUSIONS & INFERENCES: Abdominal VNS is feasible and safe in humans and has anti-inflammatory properties. As abdominal VNS improves POI similar to cervical VNS in mice, our data indicate that peroperative abdominal VNS may represent a novel approach to shorten POI in man.

Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus.

BACKGROUND: Postoperative ileus (POI) is characterized by a transient inhibition of gastrointestinal (GI) motility after abdominal surgery mediated by the inflammation of the muscularis externa (ME). The aim of this study was to identify alterations in the enteric nervous system that may contribute to the pathogenesis of POI. METHODS: Gastrointestinal transit, contractility of isolated smooth muscle strips and inflammatory parameters were evaluated at different time points (1.5 h to 10 days) after intestinal manipulation (IM) in mice. Immune-labeling was used to visualize changes in myenteric neurons. KEY RESULTS: Intestinal manipulation resulted in an immediate inhibition of GI transit recovering between 24 h and 5 days. In vitro contractility to K(+) (60 mM) or carbachol (10(-9) to 10(-4) M) was biphasically suppressed over 24 h after IM (with transient recovery at 6 h). The first phase of impaired myogenic contractility was associated with increased expression of TNF-α, IL-6 and IL-1α. After 24 h, we identified a significant reduction in electrical field stimulation-evoked contractions and relaxations, lasting up to 10 days after IM. This was associated with a reduced expression of chat and nos1 genes. CONCLUSIONS & INFERENCES: Intestinal manipulation induces two waves of smooth muscle inhibition, most likely mediated by inflammatory cytokines, lasting up to 3 days after IM. Further, we here identify a late third phase (>24 h) characterized by impaired cholinergic and nitrergic neurotransmission persisting after recovery of muscle contractility. These findings illustrate that POI results from inflammation-mediated impaired smooth muscle contraction, but also involves a long-lasting impact of IM on the enteric nervous system.

Ghrelin receptor modulates T helper cells during intestinal inflammation.

BACKGROUND: The orexigenic peptide ghrelin has anti-inflammatory properties in colitis, however, the mechanism of action and the immune cells targeted remain still to be elucidated. Here, we assessed the possible effect of ghrelin on T helper (Th) cells in a T cell transfer model of chronic colitis. METHODS: Disease was induced in the recombination activating gene 1 knockout mice (Rag1(-/-) ) by adoptive transfer of naïve Th cells from ghrelin receptor knockout mice (GRLN-R(-/-) ) or littermate wild-type (WT) mice. The course and severity of colitis was assessed by monitoring body weight, diarrhea score, histological analysis, gene expression, and flow cytometry analysis. The possible effects of ghrelin on Th cell proliferation, polarization, and apoptosis was examined in vitro. KEY RESULTS: Our data showed that Rag1(-/-) mice injected with GRLN-R(-/-) Th cells displayed increased severity of colitis compared to mice injected with WT Th cells. In addition, Rag1(-/-) mice injected with GRLN-R(-/-) Th cells had significantly higher intestinal inflammation and increased accumulation of Th1 and Th17 cells in the colon. In vitro, ghrelin directly affected proliferation of Th cells and induced apoptosis whereas it did not influence Th cell polarization. CONCLUSION & INFERENCES: Our observations suggest that ghrelin modulates Th effector cells in the gut controlling proliferation and inducing apoptosis. Our findings further support the use of ghrelin as a novel therapeutic option to treat intestinal inflammatory diseases.

[Surgical treatment of hemorrhoids using Milligan-Morgan technique. Survey of 366 cases]. / La terapia chirurgica delle emorroidi secondo Milligan-Morgan. Revisione casistica su 366 casi.

After a careful review of the Author's own case list and of the literature on this subject, Milligan-Morgans' technique is assessed and compared with different surgical techniques as far as early and late complications are concerned. The Authors conclude that the Milligan-Morgan technique is to be preferred because of its simplicity, safety and flexibility, particularly if associated with sphincterectomy, with or without rhagade, in order to prevent the cicatricial scars.

[The treatment of nonpalpable breast lesions. Our experience]. / Il trattamento delle lesioni non palpabili della mammella. Nostra esperienza.

Thanks to the diffusion of the clinico-mammographic screening, in the last ten years a considerable increase of breast carcinomas diagnosed in a subclinical stage has been registered. The authors report the preliminary results of their experience in nonpalpable lesions of the breast and confirm the validity of conservative surgery for their treatment. Nonpalpable breast carcinomas must be considered as an early stage of palpable T1 tumors, for which validity of conservative surgery is largely demonstrated. Moreover, results are not compromised by possible multicentricity and/or positivity of axillary lymph nodes.

[Use of BICAP by endoscopic route in the palliative treatment of neoplastic stenosis of the esophagus]. / L'impiego del BICAP per via endoscopica nel trattamento palliativo delle stenosi neoplastiche dell'esofago.

Over the years the palliative treatment of neoplastic stenosis of the esophagus in patients who cannot be operated has seen a variation of endoscopic methods which aimed to reopen the alimentary canal either using simple dilatation, or the insertion of endoprostheses, or sclerosing injection or antiblastic therapy, or lastly using disobstructive laser therapy. In particular, the use of Neodymium YAG laser in endoscopic therapy for the deobstruction of neoplastic esophageal stenosis is currently widely used. More recently deobstruction of the stenosis may also be achieved using bipolar diathermocoagulation with BICAP following esophageal dilatation. Recent comparative studies of the use of BICAP and laser therapy in the treatment of neoplastic esophageal stenosis have tended to reveal the complementary characteristics of the two techniques. The present paper reports the Authors' experience in this respect which has been satisfactory with regard to both methods, in line with the findings of other studies. In the study of two groups of 8 patients treated with BICAP and laser therapy respectively, recanalisation was obtained in 100% of cases with good functional results in 75% of patients treated with BICAP and 87.5% of those receiving laser therapy. The time interval between one treatment session and the next in relation to the efficacy of the therapy was similar in both methods and ranged from a minimum of 4 weeks to a maximum of 12 weeks. Complications were scarce in both groups.