Detection of KI WU and Merkel cell polyomavirus in respiratory tract of cystic fibrosis patients.

In the last few years, many reports have confirmed the presence of WU, KI and Merkel cell (MC) polyomaviruses (PyV) in respiratory samples wordwide, but their pathogenic role in patients with underlying conditions such as cystic fibrosis is still debated. To determine the prevalence of MCPyV, WUPyV and KIPyV, we conducted a 1-year-long microbiological testing of respiratory specimens from 93 patients with cystic fibrosis in Brescia, Italy. We detected PyV DNA in 94 out of 337 analysed specimens. KIPyV was the most common virus detected (12.1%), followed by WUPyV (8.9%) and MCPyV (6.8%). We found an intriguing association between the presence of MCPyV and the concurrent isolation of Pseudomonas aeruginosa, as well as with the patient status, classified as chronically colonized with P. aeruginosa. Our study adds perspective on the prevalence and the potential pathogenic role of PyV infections.

Wide nervous section to prevent post-operative inguinodynia after prosthetic hernia repair: a single center experience.

BACKGROUND: Chronic post-operative inguinodynia occurs in about 10 % of patients undergoing inguinal hernioplasty with prosthesis; it is characterized by a broad pleomorphism of symptoms, including relative to individual variability of algic perception. Its intensity can also potentially jeopardize patient's work and social activities. The most notorious cause of inguinodynia is neuropathy, resulting from the involvement of one or more inguinal nerves (iliohypogastric, ilioinguinal and genitofemoral nerves) in fibroblastic processes, or from nervous stimulation, caused by prosthetic material on adjacent nervous trunks. The aim of our study was to provide a comparative analysis between outcomes of wide nerve resection vs. nerve sparing. PATIENTS AND METHODS: In our hospital, between 2000 and 2010, 600 patients underwent monolateral prosthetic inguinal hernia repair, using the original Trabucco technique. In 345 cases, to avoid chronic post-operative pain, we carried out intentional neurectomy, between 3 and 8 cm in length of either the main and/or peripheral branches of the iliohypogastric nerve, ilioinguinal nerve and the genital branch of the genitofemoral nerve, deemed at risk of entrapment because of the prosthetic material. In the control group, which included the other 255 patients, nerves were identified and spared. Follow-up was scheduled at 1 week, 1 month and 1 year after surgery. CASE: 1 week after the operation, 135 patients (39.1 %) did not show pain, 201 (58.3 %) reported moderate pain and 9 (2.6 %) showed intense pain; 1 month after the procedure, 300 patients (87 %) did not have pain, 39 (11.3 %) complained of moderate pain and 6 (1.7 %) demonstrated severe pain; 1 year after surgery, only two patients (0.6 %) complained of persistent pain. CONTROL: At the 1-week follow-up, 114 patients (44.7 %) did not show pain, 111 (43.5 %) reported moderate pain and 30 (11.8 %) intense pain; 1 month after the procedure, 183 patients (71.8 %) did not have pain, 45 (17.6 %) complained of moderate pain and 27 (10.6%) showed severe pain; 1 year after surgery, 11 patients (4.3 %) had persistent pain, and two of them were re-submitted to surgery. The lower incidence of chronic pain after nerve resection is statistically significant (0.6 vs. 4.3 % p = 0.0048); the incidence of moderate pain 1 month after the operation is also lower (11.3 vs. 17.6 % p = 0.0097). In addition, among patients subjected to nerve resection there is a faster resolution of algetic symptomatology, over the course of a month; also noteworthy is the lower incidence of intense pain in the short-and medium-term (after 1 week, 11.8 vs. 2.6 % p = 0.0006 ; after 1 month, 10.6 vs. 1.7 % p < 0.0001). CONCLUSIONS: Despite the apparent paradox of an higher tissue damage, elective neurectomy of selected segments of inguinal nerves, appears an effective technique in preventing chronic postherniorraphy pain, considering both the lower incidence and the faster resolution of painful symptomatology.

Surgical site and early urinary tract infections in 1000 kidney transplants with antimicrobial perioperative prophylaxis.

Surgical site infections (SSIs) and early urinary tract infections (UTIs) are well recognized postoperative kidney transplant complications. These complications seldom lead to graft loss, although they may result in significant morbidity with prolonged hospitalization. Thus, perioperative antibiotic prophylaxis (PAP) has traditionally been used in this setting. Between April 1988 and December 2012, we identified 1000 kidney transplant recipients (33 from living donors) who underwent prophylaxis with ceftriaxone before the surgical procedure. A retrospective analysis was conducted to evaluate both the incidence rate and outcome of SSIs and UTIs. Recipients who developed SSIs were also assessed to identify risk factors and potential correlations with different immunosuppressive regimens. A total of 20 SSIs (2%) and 93 UTIs (9.3%) were observed. The most significant risk factor for SSIs was urine leak (15.38%; odds ratio [OR], 12.3; P < .0001) followed by sirolimus-based maintenance immunosuppression therapy (5%; OR, 2.97; P = .04) and induction therapy with either antithymocyte globulin or basiliximab (3.18%; OR, 3.45; P = .01). Sex was identified as the only risk factor for UTI (female vs male, 17.1% vs 4.6%; P < .0001). We believe universal ceftriaxone-based prophylaxis is useful for preventing SSIs and UTIs, considering its effectiveness and safety profile.

The immunomodulatory molecule pidotimod induces the expression of the NOD-like receptor NLRP12 and attenuates TLR-induced inflammation.

Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid) (PDT) is a synthetic dipeptide with in vitro and in vivo immunomodulatory properties that is largely used for treatment and prevention of infections in paediatric and disease-prone patients. However, the effects of PDT on cellular immune responses are still poorly characterized and there is little information on the mechanism of action of this compound. It has been speculated that PDT action may be exerted through the interaction with a Pattern Recognition Receptor (PRR). Therefore, to gain a further understanding of the immune pathways involved by PDT, we first decided to investigate whether PDT could modify the immune response triggered by TLR ligands. Monocytic cells were exposed to PDT then stimulated with a panel of TLR agonists. Under these experimental conditions, we observed a significant decrease in the synthesis of key proinflammatory mediators in comparison to the production observed in TLR-stimulated cells that were not treated with PDT. Using RT² Profiler PCR Array we have observed that PDT specifically up-regulates the expression of the NOD-like receptor NLRP12 mRNA in the absence of any further costimulation. Increase of NLRP12 in cells treated with PDT was confirmed using specifically designed real-time quantitative PCR and western blotting assays where a clear increase in the amount of NLRP12 protein was detected. Furthermore, in myeloid/monocytic cells we demonstrated that PDT treatment counteracts the NLRP12 reduction induced by TLR agonists. Finally, the results obtained using NLRP12 silenced cells showed that down-regulation of the proinflammatory function occurring in PDT-treated cells upon interaction with TLRs is associated with the increased levels of NLRP12 induced by PDT. To our knowledge this is the first evidence of an immunomodulatory peptide that upregulates NLRP12 and, through this molecule, antagonizes the TLR-induced inflammatory response. These results pave the way for the development of innovative therapeutic approaches aimed at controlling different pathological settings such as tumorigenesis, systemic inflammatory processes and autoimmunity, where NLRP12 plays a crucial role.

Can we pursue minimal invasive surgery in the setting of converted laparoscopic cholecystectomy? Consideration about the "MIVAC" approach.

AIM: Laparoscopic cholecystectomy (LC) is the standard of treatment for symptomatic gallstones disease. Despite surgeon's expertise and laparoscopic technical skills, at times conversion to open laparotomy is still required to carry out safely the surgical procedure. In such cases, we still pursue a minimally invasive approach based on a very short subcostal laparotomy supported by laparoscopic magnification of the reduced surgical field. We named the procedure Minimally Invasive Video-Assisted Cholecystectomy (MIVAC). In the setting of a truly minimal laparotomy, the implementation of a laparoscope makes the difference in terms of improving observation respect to naked eye, providing both details' magnification and deep field illumination. METHODS: Between 2003 and 2010, 1054 LC were performed at a single institution. Seventy-two LC were converted to open laparotomy (6.83%). Reasons for conversion included technical difficulties, aberrant biliary anatomy, dense scarring related to severe cholecystitis, biliary injuries and significant operative bleeding. Our primary endpoint was to evaluate the level of post-operative discomfort along with patient satisfaction from an aesthetic standpoint. RESULTS: Postoperative pain was comparable to LC while subcuticular running sutures ensured acceptable cosmetic results. Medium hospital stay was 24 hours. Both operative and recovery times were comparable to LC and postoperative liver function tests and routine labs did not differ significantly from the preoperative checks. CONCLUSION: The "so called" MIVAC approach appears to be a valid alternative to traditional open cholecystectomy whenever conversion to laparotomy becomes mandatory during the course of LC.

Percutaneous ultrasound-guided radiofrequency ablation of an allograft renal cell carcinoma: a case report.

BACKGROUND: Renal cell carcinomas (RCCs) are rarely described in transplanted kidneys. Available therapeutic strategies range from allograft nephrectomy to nephron-sparing procedures such as partial nephrectomy or image-guided thermal ablation. Percutaneous radiofrequency ablation (RFA) is a minimally invasive technique which provides promising oncologic outcomes in small allograft RCCs while preserving allograft function. So far, only a few cases have been reported in the transplant setting. We describe a renal transplant RCC successfully approached by ultrasound-guided RFA. METHODS: A 42-year-old renal transplant recipient developed a small subcapsular allograft RCC at 11 years after transplantation. The decline in glomerular filtration rare prompted us to preserve as much parenchyma as possible. Ultrasound-guided RFA was performed under light sedation and local analgesia in a single session with a Starbust Talon needle. RESULTS: Postablation contrast-enhanced ultrasound displayed a 25×23 mm avascular area of complete necrosis. After 3 months gadolinium-enhanced magnetic resonance imaging confirmed the absence of viable tumor tissue and while the patient did not experience any graft function reduction (serum creatinine 2.6 mg/dL). CONCLUSIONS: Image-guided RFA represents a promising therapeutic modality for small allograft RCCs in recipients with mild graft dysfunction and/or elevated surgical risk. It is associated with low morbidity and parenchymal preservation.

Embolization of pancreatic allograft arteriovenous fistula with the Amplatzer Vascular Plug 4: case report and literature analysis.

Vascular complications remain a major cause of graft loss after pancreatic transplantation. They include vascular thrombosis, pseudoaneurysm, and arteriovenous fistula (AVF). We report a case of an AVF that appeared 3 months after a simultaneous pancreas-kidney transplantation (SPKT). Doppler ultrasonography followed by magnetic resonance angiography and later angiography provided a definitive diagnosis of a mesenteric AVF. An endovascular approach is becoming the treatment of choice owing to the high risk of graft loss associated with open surgical correction. Microcoils alone, or in conjunction with detachable balloons, are frequently used; still, a new generation of vascular plugs seem to offer a therapeutic option for AVF closure, because it is a "1 shot" procedure that avoids the risk of accidental coil migration. A new-generation Amplatzer Vascular Plug 4 was deployed over the distal arterial branch of the superior mesenteric artery stump, leading to complete exclusion of the AVF and restoring normal vascular flow.

The presence of B-cell nodules does not necessarily portend a less favorable outcome to therapy in patients with acute cellular rejection of a renal allograft.

The presence of B-cell nodules in kidney biopsies of patients undergoing acute renal allograft rejection has been reported to be associated with glucocorticoid resistance and a high risk of graft failure. In an attempt to corroborate this observation, biopsies of renal transplants that evidenced Banff grade I A acute rejection were examined for the presence of B- or T-cell nodules, the detection of which was correlated with the therapeutic response. Biopsies from 14 consecutive renal transplant recipients with a diagnosis of acute cellular rejection were examined for the presence of T (CD3-positive) or B (CD20-positive) cells by immunohistochemistry. All patients were biopsied because of a rise in serum creatinine. No biopsy showed evidence of acute humoral rejection. Immunofluorescence microscopy was negative for C4d deposition in peritubular capillaries. There were no neutrophils in the peritubular or glomerular capillaries. Five patients had T-cell nodules; four had B-cell nodules; three had both T- and B-cell nodules; two had no nodules. All biopsies contained CD3-positive cells in the tubules and in the interstitium. In all but one of the patients, episodes of acute rejection were treated with steroids (one received thymoglobulin). Furthermore two patients received mycophenolate mofetil and one, sirolimus. There were no significant differences among the groups in either the initial creatinine or the creatinine after therapy. The presence of B-cell nodules in renal allograft biopsies of patients experiencing acute cellular rejection did not portend a less favorable outcome.

c-Kit-positive mast cells in portal tracts cannot be used to distinguish acute cellular rejection from recurrent hepatitis C infection in liver allografts.

Cirrhosis secondary to chronic hepatitis C virus (HCV) is the most common indication for liver transplantation. Recurrence of HCV infection in the liver allograft occurs at a high rate. The differentiation of recurrent HCV infection from acute cellular rejection (ACR) represents a difficult challenge in transplantation pathology. The c-Kit receptor is a tyrosine kinase membrane protein encoded by the c-Kit proto-oncogene, which is expressed on mast cells and on hematopoietic stem and progenitor cells. Mast cells are important effector cells of a broad range of immune responses. Recently, c-Kit+ mast cells were shown to form part of the inflammatory infiltrate in acute liver allograft rejection. A strong relationship was found between c-Kit+ cell densities and increasingly severe rejection. The present study sought to determine whether the presence of c-Kit+ cells could be used to distinguish between ACR and recurrent HCV in liver allografts. Immunohistochemical staining for c-Kit was performed on 20 transplant biopsy specimens from 10 patients with mild to moderate ACR and 10 other patients with recurrent hepatitis C. The number of c-Kit+ cells per portal tract varied with the density of the overall inflammatory infiltrate. There was no significant difference between the number of c-Kit+ cells in the biopsy specimens that carried a diagnosis of ACR and those from patients who had been diagnosed as having recurrent HCV. It was concluded that immunohistochemical staining for the presence of c-Kit+ mast cells cannot be used to differentiate between ACR and recurrent HCV infection in liver allograft biopsy specimens.

Basiliximab induction in adult liver transplant recipients with 93% rejection-free patient and graft survival at 24 months.

Induction with the use of interleukin-2 receptor monoclonal antibodies may avoid many of the adverse events associated with polyclonal antibodies and significantly impact on rejection-free long-term survival in orthotopic liver transplantation (OLTx). We describe our experience with the use of basiliximab induction therapy in adult OLTx recipients on tacrolimus-based immunosuppression. Forty-six consecutive deceased donor primary OLTx were analyzed. All patients received standard doses of basiliximab, tacrolimus, and steroids. Mycophenolate mofetil was also used as indicated. The mean follow-up period was 17.9 months. Forty-three patients remained rejection-free during follow-up. The actuarial patient and graft survival rate at 2 years was 93%. The rate of histology-proven hepatitis C virus (HCV) recurrence was 24%, with two progressing to severe cholestatic recurrent HCV. None of the study patients developed (cytomegalovirus (CMV) infection or posttransplant lymphoproliferative disease (PTLD). Results were compared to a historical group of 46 OLTx recipients on tacrolimus-based immunosuppression without basiliximab induction. The historical group had a rejection rate of 34% with lower patient and graft survival rates of 71.74% and 69.5%, respectively, at 24 months as well as a higher histological HCV recurrence rate of 77% (17/22), with three patients progressing to graft failure within 2 years. CMV infection and disease developed in 4.5% of the patients. Although PTLD was not observed, three recipients with hepatocellular carcinoma (HCC) developed and died of metastatic HCC. Induction with basiliximab in combination with tacrolimus-based immunosuppressive regimen reduces the incidence of rejection and improves rejection-free survival rate after OLTx without increasing the incidence of CMV, PTLD, or HCV recurrence.

[Pancreatic cystic metastasis from pulmonary carcinoma. Report of a case]. / Metastasi cistica pancreatica da carcinoma polmonare. Presentazione di un caso.

We report the case of a patients with a metachronous cystic pancreatic metastasis from an undifferentiated large cell lung carcinoma two years after the primary tumor had been surgically removed. Clinically, he presented with epigastric pain, fever, weakness and anorexia. The patient was operated and a palliative cystogastrostomy was performed after an intraoperative biopsy had been informed as positive for carcinoma. Six months later the patient died. Pancreatic metastases from lung carcinoma are found in approximately 7-9% of patients deceased of this neoplasm. Clinical and radiological findings simulate primary pancreatic tumors, being epigastric pain, jaundice and upper digestive bleeding the most frequent symptoms. They represent stages of advanced systemic disseminated tumoral disease, and because of this reason total or partial surgical curative resections will only be performed in a few cases of patients with isolated metastasis, criteria of resectability and without evidence of extended disease to other organs or systems. In the most of the cases, the treatment will only be palliative, even medical or surgical.