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An adult male underwent a bowel transplant for tufting enteropathy, receiving alemtuzumab, tacrolimus, and steroids as immunosuppressants. Five years later, he developed an autoimmune hemolytic anemia (AIHA), anti-IgG positive, with reduced reticulocyte count, leukopenia, and thrombocytopenia with antiplatelet antibodies. After an unsuccessful initial treatment with high dose steroids, reduction in tacrolimus dose, and intravenous immunoglobulin (IVIG), a bone marrow biopsy revealed absence of erythroid maturation with precursor hyperplasia. The patient was switched to sirolimus and received four doses of rituximab plus two courses of plasmapheresis, which decreased his transfusion requirements. After a febrile episode one month later, the AIHA relapsed with corresponding decreases in platelet and leukocyte count: cyclosporine A (CsA) was started with a second course of rituximab and IVIG without response, even though repeat bone marrow biopsy did not reveal morphology correlated to an acquired pure red cell aplasia (APRCA). Considering the similarity in his clinical and laboratory findings to APRCA, alemtuzumab was added (three doses over a week) with CsA followed by steroids. The patient was eventually discharged transfusion-independent, with increasing hemoglobin (Hb) levels and normal platelet and leukocyte count. One year later he is still disease-free with functioning graft.

One of the major limitations of thoracoscopic resection of lung nodules is localization of the target, especially when the lesion is deep or very small: we investigated the efficacy of US as a technique for intraoperative localization.We examined 11 patients who underwent diagnostic and/or curative thoracoscopic resection of benign or malignant, primary or metastatic lung nodules. The study was preceded by a preliminary phase in which we examined with US 5 patients that underwent thoracotomy. A multifrequency laparoscopic US probe with a deflectable linear headpiece mounted on a portable Esaote-Hitachi Spazio US unit was used.The US exploration of the lung requires the complete collapse of the parenchyma and is therefore particularly difficult in patients with severe chronic obstructive pulmonary disease (COPD). In the patients examined during thoracotomy US showed all the lesions but one 7-mm nodule in an emphysematous patient in whom complete parenchyma collapse could not be achieved. Also in the patients examined during thoracoscopy US detected all the targets (13/13), even a 13-mm metastatic nodule which had been visualized preoperatively by PET only. The smallest lesion found was a 4-mm fibrosarcoma metastasis. The mean time to achieve adequate lung collapse was about 40 minutes from selective exclusion of the affected lung.Thoracoscopic US has been recently introduced for the intraoperative localization of pulmonary nodules. In our experience this technique is helpful in localizing the targets, assessing the extent of surgical resection and studying possible vascular involvement. Considering the easy execution, the low cost, the lack of contraindications and complications of the technique and its accuracy when performed under optimal technical conditions, we think there are enough reasons to investigate this approach further.Intraoperative US proved to be a useful technique of easy execution, even though it is heavily operator-dependent and limited in patients with severe COPD.

The metabolic changes that occur in tumor microenvironment (TME) can influence not only the biological activity of tumor cells, which become more aggressive and auto sustained, but also the immune response against tumor cells, either producing ineffective responses or polarizing the response toward protumor activity. γδ T cells are a subset of T cells characterized by a plasticity that confers them the ability to differentiate towards different cell subsets according to the microenvironment conditions. On this basis, we here review the more recent studies focused on altered tumor metabolism and γδ T cells, considering their already known antitumor role and the possibility of manipulating their effector functions by in vitro and in vivo approaches. γδ T cells, thanks to their unique features, are themselves a valid alternative to overcome the limits associated with the use of conventional T cells, such as major histocompatibility complex (MHC) restriction, costimulatory signal and specific tumor-associated antigen recognition. Lipids, amino acids, hypoxia, prostaglandins and other metabolic changes inside the tumor microenvironment could reduce the efficacy of this important immune population and polarize γδ T cells toward IL17 producing cells that play a pro tumoral role. A deeper knowledge of this phenomenon could be helpful to formulate new immunotherapeutic approaches that target tumor metabolisms.

Adipose stem cells (ASCs) represent a reliable source of stem cells with a widely demonstrated potential in regenerative medicine and tissue engineering applications. New recent insights suggest that three-dimensional (3D) models may closely mimic the native tissue properties; spheroids from adipose derived stem cells (SASCs) exhibit enhanced regenerative abilities compared with those of 2D models. Stem cell therapy success is determined by “cell-quality”; for this reason, the involvement of stress signals and cellular aging need to be further investigated. Here, we performed a comparative analysis of genes connected with stemness, aging, telomeric length and oxidative stress, in 3D and 2D primary cultures. The expression levels of stemness-related markers and anti-aging Sirtuin1 were significantly up-regulated (P < 0.001) in SASCs-3D while gene expression of aging-related p16INK4a was increased in ASCs-2D (P < 0.001). The 3D and 2D cultures also had a different gene expression profile for genes related to telomere maintenance (Shelterin complex, RNA Binding proteins and DNA repair genes) (P < 0.01 and P < 0.001) and oxidative stress (aldehyde dehydrogenase class1 and 3) (P < 0.05, P < 0.01 and P < 0.001) and presented a striking large variation in their cellular redox state. Based on our findings, we propose a “cell quality” model of SASCs, highlighting a precise molecular expression of several genes involved with stemness (SOX2, POU5F1 and NANOG), anti-aging (SIRT1), oxidative stress (ALDH3) and telomeres maintenance.

Inflammatory bowel disease (IBD) remains a global health problem with a significant percentage of patients progressing to chronic inflammation and colitis-associated cancer (CAC). Whether or not γδ T cells contribute to initiation and maintenance of inflammation in IBD and in the development of CAC is not known. We have evaluated the frequency, phenotype, and functions of γδ T cells among tissue-infiltrating lymphocytes in healthy donors and IBD and CAC patients. Results show that Vδ1 T cells are the dominant γδ T-cell population in healthy tissue, whereas Vδ2 T significantly abound in chronic IBD. Vδ2 T cells produce more IFN-γ, TNF-α, and IL-17 than Vδ1 T cells in chronic inflamed IBD. In CAC patients no significant cytokine production was detected in tissue-resident Vδ1 T cells, but Vδ2 T cells produced remarkable amounts of IFN-γ and TNF-α; these data were confirmed by the analysis of an independent cohort of IBD transcriptomes. Moreover, transcriptomes of IBD patients revealed a clear-cut clusterization of genes related with the maintenance of the inflammatory status. In conclusion, our results demonstrating that Vδ2 T cells have a proinflammatory profile in chronic IBD are suggestive of their participation in IBD and CAC pathogenesis.

Background Anastomotic leak after ileal pouch–anal anastomosis (IPAA) could lead to poor functional results and failure of the pouch. The aim of the present study was to analyze the outcomes of the vacuum-assisted closure therapy as the unique treatment for anastomotic leaks following IPAA without any additional surgical operations. Methods Consecutive patients with anastomotic leak after IPAA treated at our institution between March 2016 and March 2017 were prospectively enrolled. After diagnosis, the Endosponge ® device was positioned in the gap and replaced until the cavity was reduced in size and covered by granulating tissue. A pouchoscopy was performed every week for the first month and monthly subsequently. No additional procedures were performed. Results Eight patients were included in the study. The leak was diagnosed at a median of 14 (6–35) days after surgery. At the time of diagnosis, seven patients had a defunctioning ileostomy performed as routine at the time of pouch formation, while one patient was diagnosed after ileostomy closure and underwent emergency diversion ileostomy. The Endosponge ® treatment started after a median of 6.5 (1–158) days after the diagnosis of the leakage and was carried on for a median of 12 (3–42) days. The device was replaced a median of 3 (1–10) times. The median length of hospital stay after the first application of the treatment was 15.5 (6–48) days. The complete healing of the leak was documented in all patients, after a median of 60 (24–90) days from the first treatment. All patients but one had their ileostomy reversed at a median of 2.5 (1–6) months from the confirmation of the complete closure. Conclusions Endosponge® is effective as the only treatment after IPAA leak. Based on the results of our prospective pilot study, application of Endosponge ® should be the treatment of choice in selected pouch anastomotic leaks not requiring immediate surgery. These results will have to be confirmed by future prospective studies including a larger number of patients.

The formation of an advancement rectal flap could be technically demanding in the presence of high perianal of rectovaginal fistula, and the outcomes could be frustrated by the inadequate view, bleeding and a poor exposure through the standard transanal approach. The application of the transanal minimally invasive surgery (TAMIS) to the advancement rectal flap procedure could overcome these difficulties. In the lithotomy position, a partial fistulectomy was performed and the internal opening was closed. A full-thickness flap was mobilized initially through the classic transanal approach. Subsequently, the TAMIS port was inserted and the mobilization of the flap was carried on proximally for as long as required. The laparoscopic visualization allowed a perfect view, a proper orientation of the flap and accurate hemostasis. The TAMIS-flap procedure seems a promising technique to perform a long advancement rectal flap to treat high perianal or rectovaginal fistulae (Video, Supplemental Digital Content 1, http://links.lww.com/SLE/A208).

Background Clinical and psychosocial outcomes of a multimodal surgical approach for chronic intestinal pseudo-obstruction were analyzed in 24 patients who were followed over a 2- to 12-year period in a single center after surgery or intestinal/multivisceral transplant (CTx). Methods The main reasons for surgery were sub-occlusion in surgery and parenteral nutrition–related irreversible complications with chronic intestinal failure in CTx. Results At the end of follow-up (February 2015), 45.5% of CTx patients were alive: after transplantation, improvement in intestinal function was observed including a tendency toward recovery of oral diet (81.8%) with reduced parenteral nutrition support (36.4%) in the face of significant mortality rates and financial costs (mean, 202.000 euros), frequent hospitalization (mean, 8.8/re-admissions/patient), as well as limited effects on pain or physical wellness. Conclusions Through psychological tests, transplant recipients perceived a significant improvement of mental health and emotional state, showing that emotional factors were more affected than were functional/cognitive impairment and social interaction.

Following a single report in the literature of granular cell tumour associated with diffuse leiomyomatosis in the oesophagus, we describe the case of a 39-year-old man in whom a granular cell tumour and two leiomyomas were endoscopically removed from this site. This previously unreported association of granular cell tumour with isolated leiomyomas suggests the need to bear in mind the possibility of other mesenchymal lesions, including leiomyomas or leiomyomatosis, when a granular cell tumour is found in the oesophagus.

Intestinal transplantation is gaining worldwide acceptance as the main option for patients with irreversible intestinal failure and complicated total parenteral nutrition course. In adults, the main cause is still represented by short bowel syndrome, but tumors (Gardner syndrome) and dismotility disorders (chronic intestinal pseudo-obstruction [CIPO]) have been treated increasingly by this kind of transplantation procedure. We reviewed our series from the disease point of view: although SBS confirmed results achieved in previous years, CIPO is nowadays demonstrating an excellent outcome similar to other transplantation series. Our results showed indeed that recipients affected by Gardner syndrome must be carefully selected before the disease is to advanced to take advantage of the transplantation procedure.

The incidence of gastro-oesophageal junction (GEJ) adenocarcinoma is increasing in Western countries and prognosis is poor since metastasis is most often present at diagnosis. We examined samples from 87 resected type II GEJ adenocarcinomas, 30 of these with endoscopic diagnostic biopsy material, to evaluate transforming growth factor alpha (TGF-α) expression and p53 overexpression by immunohistochemistry and in situ hybridization (for TGF-α), in relation to biological and clinical behaviour. TGF-α messenger RNA (mRNA) and protein were detectable in neoplastic cells in 56% and 64% cases respectively. TGF-α mRNA was detected in intra- and peritumoral lymphocytes and those of metastatic lymph nodes. TGF-α protein expression was significantly associated with tumour progression (P = 0.025) and lymph node metastasis (P < 0.05). The strong TGF-α expression found in neoplastic cells inside blood and lymphatic vessels and in metastatic localizations suggests that TGF-α-positive GEJ adenocarcinomas could have a more aggressive biological phenotype. The expression of TGF-α mRNA and protein in both inflammatory and neoplastic cells indicates that TGF-α is directly synthesized by both cell compartments. Finally, since TGF-α expression was associated with lymph node metastasis, its detection in preoperative perendoscopic biopsies might identify patients with more aggressive tumours who may need additional therapy, including neo-adjuvant treatment. (C) 2000 Cancer Research Campaign.