Tommaso Dominioni

Detergent-Enzymatic Decellularization of Swine Blood Vessels: Insight on Mechanical Properties for Vascular Tissue Engineering

Small caliber vessels substitutes still remain an unmet clinical need; few autologous substitutes are available, while synthetic grafts show insufficient patency in the long term. Decellularization is the complete removal of all cellular and nuclear matters from a tissue while leaving a preserved extracellular matrix representing a promising tool for the generation of acellular scaffolds for tissue engineering, already used for various tissues with positive outcomes. The aim of this work is to investigate the effect of a detergent-enzymatic decellularization protocol on swine arteries in terms of cell removal, extracellular matrix preservation, and mechanical properties. Furthermore, the effect of storage at −80°C on the mechanical properties of the tissue is evaluated. Swine arteries were harvested, frozen, and decellularized; histological analysis revealed complete cell removal and preserved extracellular matrix. Furthermore, the residual DNA content in decellularized tissues was far low compared to native one. Mechanical testings were performed on native, defrozen, and decellularized tissues; no statistically significant differences were reported for Youngs modulus, ultimate stress, compliance, burst pressure, and suture retention strength, while ultimate strain and stress relaxation of decellularized vessels were significantly different from the native ones. Considering the overall results, the process was confirmed to be suitable for the generation of acellular scaffolds for vascular tissue engineering.

Colonoscopy is mandatory after Streptococcus bovis endocarditis: a lesson still not learned. Case report

BackgroundEven though the relationship between certain bacterial infections and neoplastic lesions of the colon is well-recognized, this knowledge has not been sufficiently translated into routine practice yet.Case presentationWe describe the case of a 51-year-old man who was admitted to our Surgical Department due to rectal bleeding and abdominal pain. Preoperative colonoscopy, staging exams and subsequent surgery demonstrated a stenotic adenocarcinoma of the sigmoid colon, invading the left urinary tract and the homolateral bladder wall, with regional lymph nodes involvement and massive bilobar liver metastases (T4N1M1). After Hartmanns rectosigmoidectomy and despite systemic chemotherapy, a rapid progression occurred and the patient survived for only 5 months after diagnosis. Five years before detecting this advanced colonic cancer, the patient underwent aortic valve replacement due to a severe Streptococcus bovis endocarditis. Subsequent to this infection he never underwent a colonoscopy until overt intestinal symptoms appeared.ConclusionAs this case illustrates, in the unusual setting of a Streptococcus bovis infection, it is necessary to timely and carefully rule out occult colon cancer and other malignancies during hospitalization and, if a tumor is not found, to schedule endoscopic follow-up. Rigorous application of these recommendations in the case described would have likely led to an earlier diagnosis of cancer and maybe saved the patients life.

Experimental Small Bowel Transplantation From Non–Heart-Beating Donors: A Large-Animal Study

INTRODUCTION The shortage of organs in the last 20 years is stimulating the development of new strategies to expand the pool of donors. The harvesting of a graft from non-heart-beating donors (NHBDs) has been successfully proposed for kidney and liver transplantation. To our knowledge, no studies are available for small bowel transplantation using NHBDs. In an experimental setting of small bowel transplantation, we studied the feasibility of using intestinal grafts retrieved from NHBDs. MATERIALS AND METHODS Twenty five Large White piglets underwent total orthotopic small bowel transplantation and were randomly divided as follow: NHBD group (n = 15) received grafts from NHBDs; heart-beating donor (HBD) group (n = 10) received grafts from HBDs. The NHBD pigs were sacrificed inducing the cardiac arrest by a lethal potassium injection. After 20 minutes (no touch period = warm ischemia), they underwent cardiac massage, laparotomy, and aorta cannulation for flushing and cooling the abdominal organs. In HBDs, the cardiac arrest was induced at the time of organ cold perfusion. In both groups, immunosuppression was based on tacrolimus oral monotherapy. The animals were observed for 30 days. The graft absorptive function was studied at day 30 using the D-xylose absorption test. Histological investigation included HE (Hematoxilin and Eosin) microscopical analysis and immunohistological staining. RESULTS Animals in the NHBD group died due to infection (n = 3), acute cellular rejection (n = 2), technical complications (n = 2), and intestinal failure (n = 8). In the HBD group, all animals but two were alive at the end of the study. The D-xylose absorption was significantly lower among the NHBD compared with the HBD group (P < .05). CONCLUSIONS This study confirmed that intestinal mucosa is sensitive to ischemic injury. When the intestinal graft is harvested from NHBDs, the infectious-related mortality was higher and the absorptive function lower. Histological examination confirmed a higher grade of ischemic injury in the NHBD grafts that correlated with the clinical data. Therefore, this experimental study suggested that non-heart-beating donation may not be indicated for small bowel transplantation.

Surgical spacer placement prior carbon ion radiotherapy (CIRT): an effective feasible strategy to improve the treatment for sacral chordoma

BackgroundSacral chordoma (SC) is a neoplasm arising from residual notochordal cells degeneration. SC is difficult to manage mainly because of anatomic location and tendency to extensive spread. Carbon ion radiotherapy (CIRT) is highly precise to selectively deliver high biological effective dose to the tumor target sparing the anatomical structure on its path even if when SC is contiguous to the intestine, and a surgical spacer might be an advantageous tool to create a distance around the target volume allowing radical curative dose delivery with a safe dose gradient to the surrounding organs. This paper describes a double approach—open and hand-assisted laparoscopic—for a silicon spacer placement in patients affected by sacral chordoma undergoing carbon ion radiotherapy.MethodsSix consecutive patients have been enrolled for surgical spacer placement—open (three) or hand-assisted (three)—prior carbon ion radiotherapy treatment in order to increase efficacy of carbon ion radiotherapy minimizing its side effects.ResultsResults showed that silicon spacer placement for SC treatment is feasible both via laparoscopic and laparotomic approach.ConclusionsIts use might improve CIRT safety and thus efficacy for SC treatment.

Arterial Decellularized Scaffolds Produced Using an Innovative Automatic System

There is still an unmet clinical need for small-caliber artery substitution. Decellularized scaffolds in tissue engineering represent a promising solution. We have developed an innovative system for the automatic decellularization of blood vessels, used to process pig arteries. The system is able to automatically drive a decellularization process in a safe and reliable environment, with complex time patterns, using up to three different decellularization solutions, and providing at the same time a physical stress to improve the decellularization. The decellularization of pig arteries was evaluated by means of histology, DNA quantification and mechanical testing. Outcomes showed scaffolds with no cellular or nuclear remnants and a well-preserved tissue structure, corroborated by mechanical properties similar to native tissue. Decellularized scaffolds were seeded on the inner layer with human endothelial cells and implanted as iliac artery replacement in 4 pharmacologically immune-compromised pigs. This chimeric model was performed as a very preliminary evaluation to investigate the performances of these scaffolds in vivo, and to investigate the fate of seeded cells. Recipients were sacrificed on day 14 and day 70 after surgery, and vessels were found to be patent and with no evidence of thrombi formation. The inner layer was covered by endothelial cells, and the migration of cells positive for α-smooth-muscle actin was observed from the outer layer towards the tunica media. Intriguingly, the endothelial cells on explanted vessels were entirely derived from the host while the seeded cells were lost. In conclusion, this work presents a novel tool for a safe and controlled production of arterial scaffolds, with good decellularization outcomes and a good performance in a short-term, large-animal implantation.

Ventriculoperitoneal shunt and the need to remove a gallbladder: Time to definitely overcome the feeling that laparoscopic surgery is contraindicated

Since Baskin et al. reported the first documented case of failure of a laparoscopically-induced ventriculoperitoneal shunt (VP) in 1998, the cerebrospinal fluid shunt has been generally considered a relative contraindication to laparoscopy. Although the literature is limited there is a small body of evidence indicating that it is safe to perform laparoscopic surgery on these patients with routine anaesthetic monitoring. In this study we report the case of a laparoscopic cholecystectomy in the presence of a ventriculoperitoneal shunt. A review of the literature suggests that laparoscopic cholecystectomy can be safely performed in patients with a ventriculoperitoneal shunt. The only related contraindication should be if a catheter has recently been placed.

The challenge of extraabdominal desmoid tumour management in patients with Gardner's syndrome: radiofrequency ablation, a promising option

Desmoid tumours are benign, myofibroblastic stromal neoplasms common in Gardner’s syndrome, which is a subtype of familial adenomatous polyposis characterized by colonic polyps, osteomas, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The primary treatment is surgery, followed by adjuvant radiotherapy, but the local recurrence rate is high, and wide resection can result in debilitating loss of function. We report the case of a 39-year-old man with Gardner’s syndrome who had already undergone a total prophylactic colectomy. He developed desmoid tumours localized in the mesenteric root, abdominal wall and dorsal region, which were treated from 2003 through 2013 with several surgical procedures and percutaneous radiofrequency ablation. In 2008 and 2013, RFA was applied under ultrasonographic guidance to two desmoid tumours localized in the dorsal thoracic wall. The outcomes were low-grade pain and one case of superficial skin necrosis, but so far there has been no recurrence of desmoid tumours in these locations. Surgical resection remains the first-line therapy for patients with desmoid tumours, but wide resection may lead to a poor quality of life. Radiofrequency ablation is less invasive and expensive and is a possible therapeutic option for desmoid tumours in patients with Gardner’s syndrome.

Erratum: Detergent-enzymatic decellularization of swine blood vessels: Insight on mechanical properties for vascular tissue engineering (BioMed Research International)

1 Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci, 32 20133 Milano, Italy 2 PhD Program in Bioengineering, Politecnico di Milano, Piazza Leonardo da Vinci, 32 20133 Milano, Italy 3 Complication of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy 4General Surgery I, Fondazione IRCCS Pol. San Matteo, Pavia, Italy

Technical aspects of living-related liver donation: single-center experience.

Living-related donor liver transplantation is the newest and both technically and ethically most challenging evolution in liver transplantation and has contributed to reduction in donor shortage. We briefly report the technical aspects of surgical procedures performed to achieve a partial graft from a live donor. Eighty-four adult and two pediatric recipients underwent living-related donor liver transplantation at our center. There were no donor deaths, and all patients returned to their normal activities after the perioperative period. This single-center experience may contribute to refinement of the surgical technique required to improve the outcome of these complex operations.

Biliary Intraductal Papillary Mucinous Neoplasm: the “Thread Sign”

A 67-year old man was referred to our centre for recurrent acute cholangitis associated to fluctuant jaundice in the last 2 years. His medical history was positive for IBD for which the patient underwent a total proctocolectomy with ileostomy, GIST of the stomach surgically resected, type 2 diabetes mellitus and a renal vein thrombosis. Previous cholangitis was treated by repeated endoscopic stents positioning until the last hospitalization for a severe isolate obstructive jaundice, (total bilirubin 18–83 mg/dl). Spyglass allowed the direct examination of the bile duct with findings of mucinous, frond-like, floating projections suspected for biliary intraductal papillary mucinous neoplasm (B-IPMN). Biopsies were performed but results were inconclusive. After first-line radiological analysis (US), biliary drainage with ERCP has been performed (Fig. 1) with mucoid lumps at the common biliary confluence. In view of surgical intervention, hepatic-specific MRI has been accomplished with peculiar findings. MR cholangiography has presented diffuse biliary dilation particularly of left hepatic lobe (Fig. 2). MRI, in the hepato-biliary phase, showed no contrast signal in the dilated biliary tract. In particular, Fig. 2 highlights pathognomonic Bthread sign^ (dashed red line box) of B-IPMN represented by presence of hypointense striations within the extrahepatic bile duct. These radiological findings are always pathognomonic for B-IPMN. Due to its premalignant status, left hepatectomy has