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Background/Aim: COVID-19 is rapidly spreading, and due to the high morbidity and mortality caused by the pandemic many Governments have introduced social restrictions. Those measures combined with infection-related patient anxiety, led to hiding other diseases. The aim of this study was to evaluate the impact of COVID-19 on numbers and severity of acute appendicitis cases referred during the pandemic. Patients and Methods: Between March 2019 and March 2021, all patients who underwent appendectomy in Tor Vergata Hospital, Rome were included. Patients were divided in two groups (COVID-19/pre-COVID-19). Clinical features, intraoperative findings, hospital stay, and histologic examination data were included in the retrospective analysis. Results: Out of 334 admitted patients, 36 (10.7%) had a diagnosis of acute appendicitis (COVID-19 group) vs. 59(11.2%) in the pre-COVID-19 group. The COVID-19 group presented significantly longer hospitalization, incidence of appendicular abscess, perforation, and severity of inflammation at univariate analysis p=0.002, p=0.021, p=0.001, p=0.006, p=0.001, respectively. At multivariate analysis, appendicular abscess (p=0.015) and higher serum levels of C reactive protein (p

Xanthogranulomatous pyelonephritis (XGPN) is a rare disorder affecting the kidney which can fistulise to the colon in exceptional cases. We herein report a case of XGPN with renocolic fistula and large vessel thrombosis presenting with sepsis and pulmonary embolism. Preoperative diagnosis and strategic planning resulted in successful management. A 64-year-old woman presented to the emergency department with abdominal pain and a septic condition, corroborated by venous thromboembolism. Workup diagnosed a left renal abscess with calicocolic fistula. Scintigraphy confirmed a nonfunctioning left kidney. The patient underwent inferior vena cava filter placement and staged surgery. The first, damage control procedure was a loop ileostomy. Ten days later, when the patient’s conditions improved, she underwent left nephrectomy and left colectomy with primary anastomosis. Finally, a year later, the ileostomy was closed. At follow-up, the patient was well, with unremarkable renal function. Scrupulous diagnostics, multidisciplinary decision making, and staged intervention have been key to optimal outcome.

Patient: Male, 42-year-old Final Diagnosis: Neuroendocrine tumor Symptoms: Abdominal pain Medication:— Clinical Procedure: — Specialty: Surgery Objective: Unusual clinical course Background: Jejunoileal neuroendocrine tumors (JI-NETs) are rare tumors that can be associated with mesenteric fibrosis. This case report is of an incidental finding of a JI-NET in a patient who was previously misdiagnosed with sclerosing mesenteritis. Case Report: A 42-year-old man was admitted to our institution with diffuse abdominal pain and clinical and radiographic signs of bowel obstruction. He had a previous diagnosis of sclerosing mesenteritis, which had been histologically diagnosed after an exploratory laparoscopy performed in 2009 for recurrent acute abdominal pain. He was also annually monitored through computed tomography scans for an incidentally discovered, gradually enlarging mesenteric mass for which a “wait and watch” management approach was adopted. After a period of fasting and observation, the patient underwent an urgent exploratory laparotomy because of his worsening condition. Intraoperatively, an ileocecal resection was performed, along with excision of the known mesenteric mass. The pathology report revealed an ileal NET with nodal metastases within the mesentery and mesenteric tumor deposits (pT3N1). Conclusions: JI-NETs are rare entities, which are usually encountered as incidental findings or in patients with unspecific abdominal pain. Our case represents a probable delayed diagnosis of JI-NET in the context of sclerosing mesenteritis; therefore, a possible association between these 2 conditions should be investigated.

Patient: Female, 31-year-old Final Diagnosis: Appendiceal neuroendocrine tumor • low-grade appendiceal mucinous neoplasm Symptoms: Abdominal pain • dysuria Medication: — Clinical Procedure: Laparoscopic appendicectomy • laparoscopic right hemicolectomy Specialty: Oncology • Surgery Objective: Rare co-existance of disease or pathology Background: Incidental appendiceal neoplasms account for 1–2% of appendectomies. Mucinous neoplasms and carcinoids are the most frequent lesions, with an incidence of 0.6% and 0.3–0.9%, respectively. Appendiceal collision tumors are extremely rare and result from the proliferation of 2 different cellular lines. This report describes a young woman with a collision tumor composed of a low-grade appendiceal mucinous neoplasia (LAMN) and an appendiceal neuroendocrine tumor (ANET). Case Report: A 31-year-old woman was admitted to our institution presenting with abdominal pain and dysuria. After ultrasound assessment of a dilated appendix with wall thickening and distension by anechogenic material, a diagnosis of acute appendicitis was made. The patient, after a period of antibiotic therapy and observation, underwent an urgent laparoscopic appendectomy due to worsening condition. Surprisingly, the histological exam revealed a Tis LAMN extending from the base of the appendix to the resection margins, and a T3 grade-1 ANET, chromogranin-A and synaptophysin-positive, with a Ki67 less than 1%. On the basis of histological examination and European Neuroendocrine Tumor Network guidelines, in light of the positive LAMN resection margin and ANET mesoappendiceal invasion, after multidisciplinary team discussion, an elective laparoscopic hemicolectomy was indicated. The patient is now in good condition following a regular 5-year follow-up. Conclusions: A collision LAMN and ANET is an exceedingly rare condition. The heterogeneity of clinical presentation and lack of solid evidence seem to recommend a tailored management. Laparoscopy is a safe and useful tool in localized mass excision.

Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma samples were collected at different time points for SARS-CoV-2 RNA quantification by two ddPCR assays. For both patients, ddPCR revealed persistent and prolonged detection of viral RNA in the nasopharyngeal swab despite triple-negative or single-positive results by qRT-PCR. In Patient 1, SARS-CoV-2 RNA dropped more rapidly in bile and rectal-swab and declined slowly in nasopharyngeal swab and plasma, becoming undetectable in all compartments 97 days after symptoms started. Conversely, in patient 2, SARS-CoV-2 RNA was detected, even if at low copies, in all body samples (with the exception of urine) up to 75 days after the onset of symptoms. This study highlights that SARS-CoV-2 RNA can persist for a prolonged time in respiratory samples and in several biological samples despite negativity to qRT-PCR, supporting SARS-CoV-2’s ability to provoke persistent and disseminated infection and therefore to contribute to extra-pulmonary clinical manifestations.

One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft.The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free.Our study showed safety and efficacy in switching from BDT to QDT. After early (1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects.

Native nephrectomy (NN) in patients with autosomal dominant polycystic kidney disease (ADPKD) is indicated in cases of recurrent urinary tract infections and hematuria, neoplastic degeneration, and encumbrance. Timing, indication, and surgical approach of NN depends on the symptoms or policy of the center. The aim of our study is to evaluate our experience. In our retrospective study, we included 130 patients with a diagnosis of ADPKD from 530 patients evaluated for renal transplantation from 2011 to 2017. We analyzed the etiologic indication, the timing, and the complications of NN. In our cohort, 53 patients underwent open NN, 85% pre-kidney transplantation (KT), 13% post-KT, and only 1 case simultaneous with KT. In the pre-KT group, indications included: major indication was encumbrance in the. In the post-KT group, the major indication was infection followed by encumbrance, which developed after KT. Complications were: 3 cases of bleeding (1 required relaparotomy, 2 evolved into hematoma and radiological derange); 1 iatrogenic iliac artery injury, which was contextually repaired, and 5 cases of incisional hernia. At 35 ± 7.2 months follow-up, patients' survival was 96%; 1 patient died at the induction of anesthesia and 1 patient from sepsis after double NN and removal of nonfunctional transplanted kidney. NN is not without complications and should be performed when clearly indicated. In our experience, we preferred to perform NN before KT.

Background & aims We investigated the HCV-RNA amount, variability and prevalence of resistance-associated substitutions (RASs), in plasma, hepatic tumoral and non-tumoral tissue samples in patients undergoing liver-transplant/hepatic-resection (LT/HR), because of hepatocellular carcinoma and/or cirrhosis. Methods Eighteen HCV-infected patients undergoing LT/HR, 94.0% naive to direct-acting antivirals (DAAs), were analysed. HCV-RNA was quantified in all compartments. NS3/NS5A/NS5B in plasma and/or in tumoral/non-tumoral tissues were analysed using Sanger and Ultra-deep pyrosequencing (UDPS, 9/18 patients). RASs prevalence, genetic-variability and phylogenetic analysis were evaluated. Results At the time of LT/HR, HCV-RNA was quantifiable in all compartments of DAA-naive patients and was generally lower in tumoral than in non-tumoral tissues (median [IQR] = 4.0 [1.2-4.3] vs 4.3[3.1-4.9] LogIU/µg RNA; P = 0.193). The one patient treated with sofosbuvir + ribavirin represented an exception with HCV-RNA quantifiable exclusively in the liver, but with higher level in tumoral than in non-tumoral tissues (51 vs 7 IU/µg RNA). RASs compartmentalization was found by Sanger in 4/18 infected-patients, and by UDPS in other two patients. HCV-compartmentalization resulted to be associated with HBcAb-positivity (P = 0.013). UDPS showed approximately higher genetic-variability in NS3/NS5A sequences in all compartments. Phylogenetic-analysis showed defined and intermixed HCV-clusters among/within all compartments, and were strongly evident in the only non-cirrhotic patient, with plasma and non-tumoral sequences generally more closely related. Conclusions Hepatic compartments showed differences in HCV-RNA amount, RASs and genetic variability, with a higher segregation within the tumoral compartment. HBV coinfection influenced the HCV compartmentalization. These results highlight HCV-strain diversifications within the liver, which could explain some of the failures occurring even today in the era of DAAs.

Incidence of malignant tumors in kidney transplant recipients is higher than nontransplanted population due to many factors, such as immunosuppression therapy and complex donor-recipient interaction. Genitourinary malignancies have been reported as the second most common malignancy in kidney transplant recipients. In this regard, prostate cancer is the most common neoplasm. Herein, we describe a rare case of prostate cancer recurrence after 15 years in a patient who underwent kidney transplant after radical prostatectomy.

Background and objective: Liver hemangioma (LH) is the most common benign tumour of the liver, but its origin is still not clear and not much is known about a possible familiarity. Caudate lobectomy is the most effective surgical treatment for benign tumors arisen in segment I. The occurrence of giant LH within the same liver segments in different members of the same family has never been described in literature. Herein we report the first two consecutive laparoscopic caudate lobectomy for familiar giant LH in a father and his daughter. Methods: The father showed a lesion in the caudate lobe (CL) suggestive of LH steadily grown, asymptomatic for 24 years until it has caused abdominal discomfort and pain (Dmax 89 mm). The daughter showed multiple hepatic hemangiomas with the biggest one located in the CL compressing the inferior vena cava (Dmax 88 mm). Results: Despite the size of the masses, we opted for a pure laparoscopic approach and a caudate lobectomy was performed in both cases. Operation time was 140 and 180 min. Patients had an uneventful recovery and a good outcome after the scheduled follow up exams 6 months after the procedure. Conclusions: A chance of familiarity transmission for hemangiomas exists and therefore should be further investigated. Laparoscopic isolated caudate lobectomy for symptomatic GLH is feasible and safely performed on selected patients by experienced hepatobiliary surgeons. Prospective randomized studies on larger populations are needed to assess if this minimally invasive approach can be proposed as a standard of care for S-I LH.

Lifelong immunosuppression (IS) after liver transplantation is associated with severe adverse effects and increased recipients' morbidity and mortality. Clinical operational tolerance has been reported in up to 40% in very well-selected recipients. Longterm survival and cost savings within the Italian national health system in operational tolerant recipients is reported. Seventy-five liver recipients were enrolled for IS withdrawal at our institution during the period from April 1998 to December 2015. The study population comprised 32 (42.7%) tolerant patients; 41 (54.7%) nontolerant patients needing uptake of IS after clinical or biopsy-proven rejection; and 2 (2.7%) immediate nontolerant patients who developed early rejection after the first drug reduction. The primary endpoint of the study was to assess the longterm patients and graft outcome; the secondary endpoint was the assessment of cost savings in the context of IS withdrawal. The follow-up was 95.0 months (interquartile range, 22.5-108.5 months). IS withdrawal did not result in patient nor graft loss and resulted in a major cost savings reaching about €630,000. In conclusion, longterm IS withdrawal represents a remarkable cost savings in the health care of liver recipients without exposing them to graft loss.

This cohort study assessed, in Italy, the overall pattern of risk of de novo malignancies following liver transplantation (LT). The study group included 2,832 individuals who underwent LT between 1985 and 2014 in nine centers all over Italy. Person-years (PYs) at cancer risk were computed from 30 days after LT to the date of cancer diagnosis, to the date of death or to the end of follow-up. Excess cancer risk, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). During 18,642 PYs, 246 LT recipients developed 266 de novo malignancies, corresponding to a 1.8-fold higher cancer risk (95% CI: 1.6-2.0). SIRs were particularly elevated for virus-related malignancies, including Kaposi's sarcoma (SIR = 53.6, 95% CI: 30.0-88.5), non-Hodgkin lymphomas (SIR = 7.1, 95% CI: 4.8-10.1) and cervix uteri (SIR = 5.4, 95% CI: 1.1-15.8). Among virus-unrelated malignancies, elevated risks emerged for head and neck (SIR = 4.4, 95% CI: 3.1-6.2), esophagus (SIR = 6.7, 95% CI: 2.9-13.3) and adrenal gland (SIR = 22.9, 95% CI: 2.8-82.7). Borderline statistically significant elevated risks were found for lung cancer (SIR = 1.4, 95% CI: 1.0-2.1) and skin melanoma (SIR = 2.6, 95% CI: 1.0-5.3). A reduced risk emerged for prostate cancer (SIR = 0.1, 95% CI: 0.0-0.5). These findings underline the need of preventive interventions and early detection of malignancies, specifically tailored to LT recipients.

Aim We designed a retrospective case-control study to determine the efficacy and feasibility of everolimus (EVR) combined with low-dose tacrolimus (Tac) ab initio versus standard-dose Tac after liver transplantation (LT). Methods Seventy-one adult LT patients, receiving EVR and low-dose Tac without corticosteroids or induction therapy from postoperative day 1 (EVR group) were compared with a well-matched control group of 61 recipients treated with standard-dose Tac in association with antimetabolite. Results Baseline characteristics for the two groups were comparable. The overall patient and graft survival rates were similar (P = .908). Liver function was stable during the follow-up. In the EVR group, biopsy-proven acute rejection occurred in two cases (2.8%), whereas chronic rejection occurred in one (1.4%). The EVR group experienced a better renal function already after 2 weeks (estimated glomerular filtration rate: 89.85 [36.46 to 115.3] mL/min/1.73 m2 vs. 68.77 [16.11 to 115.42] mL/min/1.73 m2; P = .013), which was also observed after a median time of 27 months (range, 0 to 82 months) from LT (estimated glomerular filtration rate: 80 [45 to 118.3] mL/min/1.73 m2 vs. 70.9 [45 to 88.4] mL/min/1.73 m2; P = .04). After a median time of 27 months, the EVR group showed lower incidence of arterial hypertension and insulin-dependent diabetes mellitus. Conclusion Ab initio EVR-based immunosuppression could be a valid option immediately after surgery in recipients at high-risk for post-LT renal impairment.

Although donor-specific antibodies are regarded as a contraindication for kidney transplantation, the data available for combined liver and kidney transplantation (cLKTx) are scarce, and there is no established therapeutic approach for this category of transplant recipients. De novo use of everolimus and a reduced dose of calcineurin inhibitor reportedly provides excellent kidney function compared with a standard regimen containing a calcineurin inhibitor. This strategy, however, has been applied in only some recipient categories. Here we report a case of A highly sensitized male patient who underwent a cLKTx and received everolimus with low-dose tacrolimus (once-daily prolonged-release formulation) as ab initio immunosuppressive treatment. The pretransplant panel-reactive antibody estimate was 97%, and multiple anti-HLA antibodies were detected at the time of transplantation. Thus far, patient and allograft survival have reached 2 years, with the recipient remaining on a regimen of immunosuppression with everolimus and low-dose tacrolimus, with no episodes of rejection.

Background & aims We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Methods Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N = 18) or liver resection (N = 4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/106 liver-cells, respectively. Results HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho = 0.544, p = 0.024). Three DAA-treated patients were HCV-RNA “undetectable” in serum, but still “detectable” in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA “undetectability” in liver-tissue. Conclusions HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was “undetectable” in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available

Background and aim Everolimus (EVR) use in liver transplantation (OLT) has been prescribed with calcineurin inhibitors (CNIs), steroids, and monoclonal antibodies. The aim of our study was to evaluate the safety, feasibility, and impact on renal function of EVR ab initio, in combination with enteric-coated mycophenolate sodium (EC-MPS) without the use of induction treatment, steroids, or CNIs. Patients and methods We retrospective analyzed nine consecutive patients who underwent OLT at our institution. The initial dose of EVR (1.5 mg/d) was adjusted to achieve trough levels of 8 to 12 ng/mL. EC-MPS introduced at 1080 mg/d was maintained at the same dose over time. Results At a mean follow-up of 21.48 (standard deviation [SD] 1.4) months from OLT, 7/9 recipients were alive with stable graft function. The 2-year patient and graft survivals were 77%. One recipient died due to cerebral hemorrhage and one, lung failure. No clinical evidence of an acute rejection episode was observed. Mean estimated glomerular filtration rate value, according to the Modification of Diet in Renal Disease formula increased from 59.5 (SD 9.89) mL/min/1.73 m 2 at OLT to 100.2 (SD 47.5) mL/min/1.73 m 2 ( P = .03) after 12 months and 98.71 (SD 33.74) mL/min/1.73 m 2 ( P = .03) after 24 months' follow-up. Conclusion A double immunosuppression therapy with EVR and EC-MPS ab initio seemed to be efficacions and safe, representing a valid alternative to CNIs to prevent renal failure after OLT.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

Sofosbuvir (SOF) treatment ± ribavirin (RBV) prior to LT has the potential to change the HCV recurrence after Liver Transplantation (LT). This approach has been reported to avoid graft reinfection in compensated patients with hepatocellular carcinoma (HCC), but only among those who reached and maintained undetectable HCV-RNA (TND) before LT. Since the time to obtain this result in decompensated cirrhotics is unknown, we sought to investigate the early HCV-RNA decay in this setting. Sixteen decompensated patients (M/F 12/4, median age 55.3, CPT score>=B7), infected by HCV genotype 1a, 1b, 3 and 4 (2-8- 4-2), 4 of whom with HCC, were treated with SOF 400mg/day and RBV (200-1000 mg/day), except 2 who received SOF alone, for a median(IQR) of 12(11-16) weeks awaiting LT. HCV-RNA levels were measured weekly and safety and clinical parameters were analyzed. No serious adverse events were reported. The median(IQR) RBV dose was 600(400-800). Despite 11/16 patients had low baseline viremia (

Background There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line. Methods We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation. The primary endpoint was the incidence of SSI; the assessment of other infection in the first postoperative month was the secondary endpoint. Results Two hundred five patients were enrolled and randomized to receive either a single (n = 103) or multidose antibiotic regimen (n = 102) for prophylaxis. The incidences of SSI and urinary tract infection were similar in both groups. Conclusion As the dramatic increase in antibiotic resistance has mandated the implementation of global programs to optimize the use of antibiotic agents in humans, we believe that the single dose regimen is preferred, at least in nondiabetic, non-morbidly obese, adult renal transplant recipients.

Immunologic alterations, such as cryoglobulinemia, have been described in the acute phase of primary cytomegalovirus (CMV) infections in immunocompetent patients. There are few references about these influences of a primary CMV infection in an at-risk kidney transplant recipient (donor positive/recipient negative-D(+)/R(-)). Herein we have described the case of a 46-year-old man, who was naive for CMV and underwent renal transplantation from a CMV+ cadaveric donor, thereby at high risk for disease transmission. The immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. The recipient was not treated with CMV prophylaxis, but rather regularly screened for possible pre-emptive treatment. At 35 days after transplantation, he was admitted because of deep vein thrombosis (DVT) in the transplant ipsilateral lower limb accompanied by oliguria, fever, and epigastric pain accompanied by type II cryoglobulinemia and acute CMV infection. The direct antiglobulin test (DAT) for C3d was positive. The cryoglobulins displayed anti-red blood cell specificity, with maximum activity at 4°C. The DVT was successfully treated with locoregional thrombolysis in combination with anticoagulant therapy. The DAT improved with CMV treatment and increased steroid therapy. The urine output and renal function tests improved with resolution of the thrombosis, achieving complete recovery without sequelae. Our hypothesis was that CMV infection triggered cryoglobulinemia. The blood disorder caused hyperviscosity, inducing DVT. This case, of CMV infection showed associated cryoglobulinemia presenting with antierythrocyte specificity in a kidney transplant recipient.

AIM: To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients. METHODS: We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors (CNI group, n = 21) and mycophenolate (MMF group, n = 15) monotherapy, with those patients who successfully withdrawn immunosuppression (IS) therapy from at least 3 years (TOL group, n = 10). To perform the well-matched analysis, all HCV transplanted patients from December 1993 were screened. Only those HCV patients who reached the following criteria were considered for the analysis: (1) at least 3 years of post-operative follow-up; (2) patients with normal liver graft function under low dose CNI monotherapy (CNI group); (3) patients with normal liver graft function under antimetabolite (Micophenolate Mofetil or coated mycophenolate sodium) monotherapy (MMF group); and (4) recipients with normal liver function without any IS. We excluded from the analysis recipients who were IS free or under monotherapy for < 36 mo, recipients with cirrhosis or with unstable liver function tests. RESULTS: Thirty six recipients were enrolled in the study. Demographics, clinical data, time after LT and baseline liver biopsies were comparable in the three groups. After six years of follow-up, there was no worsening of hepatic fibrosis in the MMF group (2.5 ± 1.5 Ishak Units vs 2.9 ± 1.7 Ishak Units, P = 0.5) and TOL group (2.7 ± 10.7 vs 2.5 ± 1.2, P = 0.2). In contrast, a significant increase in the fibrosis score was observed in the CNI group (2.2 ± 1.7 vs 3.9 ± 1.6, P = 0.008). The yearly fibrosis progression rate was significantly worse in the CNI group (0.32 ± 0.35) vs MMF group (0.03 ± 0.31, P = 0.03), and TOL group (-0.02 ± 0.27, P = 0.02). No differences have been reported in grading scores for CNI group (2.79 ± 1.9, P = 0.7), MMF group (3.2 ± 1.5, P = 0.9) and TOL group (3.1 ± 1.4, P = 0.2). Twenty four patients were treated with low dose ribavirin (8 TOL, 7 MMF, 9 CNI). The hepatitis C titers were comparable in the three groups. No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period. CONCLUSION: IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients.

Objective The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. Methods Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990–2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/103 PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2–1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. Conclusions These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

Advagraf is a new modified-release once-daily formulation of tacrolimus. The aim of this study was to define the efficacy and safety of switching from Prograf to Advagraf immunosuppression in kidney transplant recipients. The switched dose ratio of Prograf to Advagraf was 1:1. Forty-one patients (34 men and 7 women) were switched at 36.6 ± 16.1 months after kidney transplantation. All patients maintained stable renal function and the conversion. In 16 subjects it was possible to withdraw steroid administration after obtaining adequate Advagraf blood levels, among whom 14 remained steroid free. Adverse events, including dizziness and tinnitus, were reported in 1 patient, who was reverted to Prograf. One patient who was receiving triple therapy with low tacrolimus blood levels experienced are acute rejection episode. The switch to Advagraf was safe and efficacious in kidney transplant recipients with or without steroid administration. Moreover, interruption of steroid was possible and well tolerated after achieving adequate stable blood levels with Advagraf.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

Herein, we report the case of a 52-year-old man with a spermatic cord liposarcoma that developed 4 years after renal transplantation. The patient was admitted with a diagnosis of inguinal hernia. During surgical exploration, a solid mass was found arising from the spermatic cord. Histologic analysis demonstrated a well-differentiated sclerosing liposarcoma.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal; cirrhosis develops in up to 30% of cases. Currently there is interest in the midterm outcomes of HCV patients with concomitant hepatitis B virus (HBV) infection among OLT recipients. We therefore retrospectively analyzed our database of patients who underwent OLT for HCV-HBV-related cirrhosis. Between April 1992 and December 2008, 350 patients underwent OLT, including 20 (5.7%) transplanted for HBV-HCV cirrhosis. We assessed patient and graft survivals at 1 and 5 years, as well as the progression of fibrosis. Protocol liver biopsies were available yearly after OLT. The survival curves were analyzed by the Kaplan-Meier approach and chronic hepatitis evaluated according to the Ishak scoring system. At a median follow-up of 68.4 +/- 53 months, the 1- and 5-year patient and graft survival rates were 80% and 70%, respectively. The 5-year fibrosis progression rate was 0.17 +/- 0.08 units of fibrosis. The only patient who developed histologic cirrhosis within 10 years of follow-up showed a lamivudine-resistant HBV recurrence. Patients transplanted for HBV-HCV coinfection showed a lower fibrosis progression rate compared with HCV monoinfected subjects.

Introduction Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. Methods Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10–252) after kidney transplantation: metastatic gastric cancer ( n = 1), metastatic colon cancer ( n = 1), bilateral nephrourothelioma ( n = 1), skin cancer ( n = 2), Kaposi's sarcoma ( n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 ( n = 1), MALT lymphoma ( n = 1), intramucous colon carcinoma ( n = 1), liposarcoma of the spermatic cord ( n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids ( n = 6) or with mycophenolate mofetil ( n = 6). Results Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7–56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up. Conclusion Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.

Introduction Breast fibroadenomas may result from exposure to cyclosporine (CsA). The aim of this prospective study was to assess the reversibility of breast fibroadenomas following conversion from CsA to tacrolimus among a small cohort of female renal transplant recipients. Methods Following renal transplantation, fibroadenomas either developed or progressed in eight Caucasian female patients with CsA-based immunosuppression. These patients were enrolled in a pilot study assessing whether conversion from a CsA-based to a tacrolimus-based regimen prevented progression of breast disease or reversed existing lumps. Patients underwent a baseline visit in which we assessed the clinical history, number and dimension of fibroadenomas, graft function and hormonal profile (FSH prolactin, estradiol and progesterone). Twenty-one lumps were described in six patients; in addition, two patients had “grapes of fibroadenomas,” of nondefinable numbers. Results Patients underwent conversion to tacrolimus after a mean of 63.8 ± 37.4 months after renal transplantation. Of the 21 clearly described lumps complete reversibility was observed for eight fibroadenomas. Other fibroadenomas either decreased in size or remained stable without further progression. These changes were reported within 1 year following conversion to tacrolimus. Conclusion A switch from CsA to tacrolimus was effective to prevent the progression of fibroadenomas. In female renal transplant recipients with CsA-based immunosuppression suffering from breast fibroadenomas, early CsA withdrawal may avoid the need for breast surgery.

Introduction. Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. Methods. Eight patients developed the following malignancies after kidney transplantation (mean 102.6 months; range 12 to 252): metastatic gastric cancer (n 1), metastatic colon cancer (n 1), bilateral nephrourothelioma (n 1), skin cancer (n 1), Kaposi’s sarcoma (n 2), posttransplant lymphoproliferative disorder (PTLD) (n 2). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n 2), associated with steroids (n 4) or mycophenolate mofetil (n 2). Results. Both patients with metastatic cancer underwent chemotherapy and then succummbed after 6 and 13 months. After a mean follow-up of 20.3 months (range 2 to 47), the remaining six patients are free from cancer disease. Renal graft function was unchanged from diagnosis throughout the follow-up. Conclusion. Our observations suggested that rapamycin-based immunosuppression offered the possibility of regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was attributed to Rapamycin treatment or to the reduced immunosuppression.

A 72-year-old male patient was admitted to our hospital for he onset of epigastric and right upper quadrant abdominal pain, omiting, chills and fever. Previous history was unremarkable. aboratory tests were normal except for a slight increase in ransaminases. After abdominal ultrasonography, he underwent ntravenous and oral contrast enhanced computed tomography, howing a gastric fistula with an abscess (maximum dimensions 3 cm × 9 cm) in segment II and IV of the liver (Fig. 1). The esophagogastroduodenoscopy revealed a foreign body odged in a pre-pyloric wall fistula (Fig. 2) most likely a toothpick, esponsible for the gastric lesion and liver collection. Percutaneous adiological collection drainage was performed and the fistula was

Background In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. Methods A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998–2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15–1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42–2.45 for age 40–59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89–10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06–4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46–2.22), oral cavity (SIR = 2.42, 95% CI: 1.36–4.00), and Kaposi’s sarcoma (SIR = 10.29, 95% CI: 1.25–37.16). Conclusions The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.