Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

BACKGROUND: The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. METHODS: A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2) were also utilized. RESULTS: Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. CONCLUSION: This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Neurological complications after liver transplantation as a consequence of immunosuppression: univariate and multivariate analysis of risk factors.

Neurological complications (NCs) can frequently and significantly affect morbidity and mortality of liver transplant (LT) recipients. We analysed incidence, risk factors, outcome and impact of the immunosuppressive therapy on NC development after LT. We analysed 478 LT in 440 patients, and 93 (19.5%) were followed by NCs. The average LOS was longer in patients experiencing NCs. The 1-, 3- and 5-year graft survival and patient survival were similar in patients with or without a NC. Multivariate analysis showed the following as independent risk factors for NC: a MELD score ≥20 (OR = 1.934, CI = 1.186-3.153) and an immunosuppressive regimen based on calcineurin inhibitors (CNIs) (OR = 1.669, CI = 1.009-2.760). Among patients receiving an everolimus-based immunosuppression, the 7.1% developed NCs, vs. the 16.9% in those receiving a CNI (P = 0.039). There was a 1-, 3- and 5-year NC-free survival of 81.7%, 81.1% and 77.7% in patients receiving a CNI-based regimen and 95.1%, 93.6% and 92.7% in those not receiving a CNI-based regimen (P < 0.001). In patients undergoing a LT and presenting with nonmodifiable risk factors for developing NCs, an immunosuppressive regimen based on CNIs is likely to result in a higher rate of NCs compared to mTOR inhibitors.

Results of salvage liver transplantation.

BACKGROUND & AIMS: Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). METHODS: Between 2000 and 2011, 125 patients (72 transplantable) underwent LR and 226 underwent LT in our unit. The outcome of SLT was analysed in a two-step fashion: firstly, SLT (n = 28) was compared with PLT (n = 198), secondly an intention-to-treat analysis was performed on all transplantable HCC patients who underwent LR (LRT group = 72) compared to PLT (n = 198). RESULTS: The five-year overall survival (OS) was 65.4% vs. 49.2% (P = 0.63), and disease-free survival (DFS) was 89.7% vs. 80.6% (P = 0.31) for PLT and SLT respectively. Predictive factors for DFS after LT included HCC total diameter [hazard ratio (HR) 1.29 P = 0.003], alpha-foetoprotein (HR 1.002 P < 0.001) and number of HCC nodules (HR 1.317 P = 0.035), whereas viral hepatitis C positivity (HR 1.911 P = 0.03) and outside Up-to-seven criteria (HR 2.652 P < 0.001) were negative independent prediction factors of OS. Intention-to-treat analysis showed that OS at 5 years was improved in PLT vs. LRT (LRT n = 72 including SLT plus LR group) and was 69.4% vs. 42.2% (P < 0.004), with an additional increase in DFS (89.2% vs. 54.5% respectively P < 0.001). CONCLUSION: Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.

Multicenter italian experience in liver transplantation for hepatocellular carcinoma in HIV-infected patients.

BACKGROUND: The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS: We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS: HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION: LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

A national survey on the current status of minimally invasive gastric practice on behalf of GIRCG.

Italian Research Group for Gastric Cancer (GIRCG), during the 2013 annual Consensus Conference to gastric cancer, stated that laparoscopic or robotic approach should be limited only to early gastric cancer (EGC) and no further guidelines were currently available. However, accumulated evidences, mainly from eastern experiences, have supported the application of minimally invasive surgery also for locally advanced gastric cancer (AGC). The aim of our study is to give a snapshot of current surgical propensity of expert Italian upper gastrointestinal surgeons in performing minimally invasive techniques for the treatment of gastric cancer in order to answer to the question if clinical practice overcome the recommendation. Experts in the field among the Italian Research Group for Gastric Cancer (GIRCG) were invited to join a web 30-item survey through a formal e-mail from January 1st, 2020, to June 31st, 2020. Responses were collected from 46 participants out of 100 upper gastrointestinal surgeons. Percentage of surgeons choosing a minimally invasive approach to treat early and advanced gastric cancer was similar. Additionally analyzing data from the centers involved, we obtained that the percentage of minimally invasive total and partial gastrectomies in advanced cases augmented with the increase of surgical procedures performed per year (p = 0.02 and p = 0.04 respectively). It is reasonable to assume that there is a widening of indications given by the current national guideline into clinical practice. Propensity of expert Italian upper gastrointestinal surgeons was to perform minimally invasive surgery not only for early but also for advanced gastric cancer. Of interest volume activity correlated with the propensity of surgeons to select a minimally invasive approach.

Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation.

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no-IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.

Development and Multicenter Validation of a Novel Immune-Inflammation-Based Nomogram to Predict Survival in Western Resectable Gastric and Gastroesophageal Junction Adenocarcinoma (GEA): The NOMOGAST.

Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation cohort (VC) of patients undergoing radical surgery for c/uT2-T4 and/or node-positive GEA were retrieved, and potentially interesting variables were collected. Cox proportional hazards in univariate and multivariate regressions were used to assess the effects of the prognostic factors on OS. A graphical nomogram was constructed using R software's package Regression Modeling Strategies (ver. 5.0-1). The performance of the prognostic model was evaluated and validated. Results. The TC and VC consisted of 185 and 151 patients. ECOG:PS > 0 (p < 0.001), angioinvasion (p < 0.001), log (Neutrophil/Lymphocyte ratio) (p < 0.001), and nodal status (p = 0.016) were independent prognostic values in the TC. They were used for the construction of a nomogram estimating 3- and 5-year OS. The discriminatory ability of the model was evaluated with the c-Harrell index. A 3-tier scoring system was developed through a linear predictor grouped by 25 and 75 percentiles, strengthening the model's good discrimination (p < 0.001). A calibration plot demonstrated a concordance between the predicted and actual survival in the TC and VC. A decision curve analysis was plotted that depicted the nomogram's clinical utility. Conclusions. We externally validated a prognostic nomogram to predict OS in a joint independent cohort of resectable GEA; the NOMOGAST could represent a valuable tool in assisting decision-making. This tool incorporates readily available and inexpensive patient and disease characteristics as well as immune-inflammatory determinants. It is accurate, generalizable, and clinically effectivex.

Short-term and long term morbidity in robotic pancreatic surgery: a systematic review.

BACKGROUND: Pancreatic cancer is one of the most aggressive and lethal tumours in Western society. Pancreatic surgery can be considered a challenge for open and laparoscopic surgeons, even if the accuracy of gland dissection, due to the close relationship between pancreas, the portal vein, and mesenteric vessels, besides the reconstructive phase (in pancreaticoduodenectomy), lead to significant difficulties for laparoscopic technique. Minimally invasive pancreatic surgery changed utterly with the development of robotic surgery. However, this review aims to make more clarity on the influence of robotic surgery on long-term morbidity. METHODS: A systematic literature search was performed in PubMed, Cochrane Library, and Scopus to identify and analyze studies published from November 2011 to September 2020 concerning robotic pancreatic surgery. The following terms were used to perform the search: "long term morbidity robotic pancreatic surgery". RESULTS: Eighteen articles included in the study were published between November 2011 and September 2020. The review included 2041 patients who underwent robotic pancreatic surgery, mainly for a malignant tumour. The two most common robotic surgical procedures adopted were the robotic distal pancreatectomy (RDP) and the robotic pancreaticoduodenectomy (RPD). In two studies, patients were divided into groups; on the one hand, those who underwent a robotic pancreaticoduodenectomy (RPD), on the other hand, those who underwent robotic distal pancreatectomy (RDP). The remaining items included surgical approach such as robotic middle pancreatectomy (RMP), robotic distal pancreatectomy and splenectomy, robotic-assisted laparoscopic pancreatic dissection (RALPD), robotic enucleation of pancreatic neuroendocrine tumours. CONCLUSIONS: Comparison between robotic surgery and open surgery lead to evidence of different advantages of the robotic approach. A multidisciplinary team and a surgical centre at high volume are essential for better postoperative morbidity and mortality.

Complication of Hirschsprung's disease immediately after pregnancy: A rare case report.

INTRODUCTION AND IMPORTANCE: Hirschprung's disease (HD) is a rare congenital colonic disorder that may develop in adult age, often determining a poor life quality with complications needing an emergency surgical setting. The disease rarely presents as an acute intestinal obstruction like SV, which represents an abdominal emergency issue. CASE PRESENTATION: A few days after discharge from gynecology unit because of her first childbirth, a young woman with HD developed colonic obstruction due to sigmoid volvulus, which was treated with Hartmann's procedure. CLINICAL DISCUSSION: Some months later, the patient underwent a two-stage Duhamel's procedure to restore the digestive tract's continuity. Both hospital periods were free of critical events. CONCLUSION: The woman regained a good quality of life: Duhamel's procedure revealed as a safe technique to use in HD adult.

The using of sealants in pancreatic surgery: A Systematic Review.

BACKGROUND: POPF derives from the pancreatic stump, which follows pancreatic resection and the pancreatoenteric anastomosis following pancreaticoduodenectomy. Since 1978 sealants have been used in pancreatic surgery to prevent pancreatic fistula after resection of the pancreatic head and tail or for the management of trauma and the treatment of low-output pancreatic fistula. Different types of fibrin sealants have been evaluated for their potential to reduce the occurrence of POPF. METHODS: A systematic search of the electronic literature was performed using PubMed, Cochrane Library, and Scopus databases to obtain access to all publications, especially clinical trials, randomised controlled trials, and systematic reviews concerning fibrin sealants pancreatic surgery. Searching for "fibrin sealants pancreas," we found a total of 73 results on Pubmed, 61 on Scopus, and 14 on Cochrane Library (148 total results). RESULTS: Eighteen studies were found on literature, following the criteria already described, concerning the use of fibrin sealants in pancreatic surgery. All articles described were published in the period between 1989 and 2019.Most of these were single centre studies. A total of 1032 patients were enrolled in this review. In the studies, sealants were used to reinforce pancreatic anastomoses and for the occlusion of the main pancreatic duct. CONCLUSION: CR-POPF is a fearful complication of pancreatic surgery; among the possible solutions to reduce the risk of onset, sealants were used on the pancreatic stump; today the sealants should be considered such as an option to reduce the CR-POPF, but the routine use in clinical practice has to be validated.

Sirolimus monotherapy effectiveness in liver transplant recipients with renal dysfunction due to calcineurin inhibitors.

INTRODUCTION: Among the adverse effects of different calcineurin inhibitors (CIs), nephrotoxicity is the most common (incidence: 18.1% at 13 y from liver transplantation) and depends on a variable degree of tubular-interstitial injury accompanied by focal glomerular sclerosis. A new immunosuppressive drug was introduced in solid organ transplant management, Sirolimus (SRL). It is a nonnephrotoxic immunosuppressor. METHODS: Twenty-six patients who developed nephrotoxicity owing to CIs, showing an increment of serum creatinine levels (>1.8 mg/dL) were switched to SRL monotherapy, initially at a dosage between 3 and 5 mg/d, and subsequently adapted to achieve trough level between 8 to 10 ng/mL. RESULTS: Patients were followed-up for a mean period of 40.3 months (range, 8.4 to 76.7) from liver transplantation. Mean follow-up after switch was 27.5 months (range, 2 to 71.2). Immunosuppression therapy was converted after a mean period of 12.8 months (range, 0.2 to 43.4). Serum creatinine, urea, and estimated glomerular filtration rate were significantly improved. DISCUSSION: Patients developing renal dysfunction after liver transplantation may be successfully treated by conversion from CI to SRL. Hypertriglyceridemia and hypercholesterolemia represent the principal side effects from SRL, but are treatable. Furthermore, SRL can significantly improve glucose tolerance.

Kaposi's sarcoma after liver transplantation.

INTRODUCTION: Kaposi's Sarcoma (KS) is a malignant neoplasm arising from endothelial cells. HHV8-infection represents a key pathogenic determinant for the development of KS. There are no standard criteria to treat KS in immunosuppressed-individuals. Six cases (2.1%) of KS occurred in our Center among 285-recipients who underwent liver transplantation (LT) between October 2000 and November 2006. METHODS: Patients were four males and two females. Mean age was 57 years (range 44-65). Indication for LT was ESLD associated/non-associated with hepatocellular carcinoma (HCC). The immunosuppressive regimen consisted of cyclosporine/tacrolimus associated with steroids or daclizumab. HHV8-detection was performed by the serological method before LT, and by polymerase chain reaction (PCR)-analysis after KS. RESULTS: One patient had HCV-related cirrhosis and coinfection from HIV, three had HBV-related cirrhosis, two of these with coexistent HCC. The last two patients had alcoholic-cirrhosis, one with coexistent HCC. Mean time from transplantation to KS was 6.2 months (range 3.8-8.8). Three patients were treated with doxorubicin and three with switch from calcineurin-inhibitors to sirolimus. Three patients expired after 11.5, 8.8, and 7.4 months from KS diagnosis. DISCUSSION: KS should be treated by a multidisciplinary approach to obtain an early diagnosis and best management. Effective treatment with immunosuppression reduction or switch to sirolimus is mandatory and can induce complete regression.

High dose rabbit antithymocyte globulin induction in living related liver transplantation.

BACKGROUND/AIMS: Induction with rabbit antithymocyte globulin (RATG) has been reported to be effective in cadaveric liver transplantation. The aim of this study was to compare two immunosuppressive protocols in adult living-related liver transplantation (LRLT). METHODOLOGY: From May 2001 through May 2003, 34 LRLT were performed. The first 17 patients (group 1) were treated with tacrolimus (TAC) and steroids. The next 17 patients (group 2) were treated with a steroid-sparing protocol using RATG. RESULTS: The one-year patient and graft survival was respectively 76.5% and 64.7% for group 1 and 88.2 and 76.5% for group 2 (p = 0.037 and p = NS, respectively). Incidence of acute cellular rejection was 41.2% in group 1 compared to 47% in group 2 (p = NS). Mean daily TAC dose at 6 months was 6.5 +/- 1.1 mg/day in group 1 and 3.2 +/- 0.9 mg/day in group 2 (p < 0.001). In group 1, 41.1% experienced CMV infection compared to 11.7% in group 2 (p = NS). CONCLUSIONS: These results suggest that this approach of RATG induction followed by postoperative, steroid-free, and low-dose TAC is safe and provides for adequate immunosuppression and similar outcome when compared to controls treated with standard TAC and steroid immunosuppression.

Multicenter Prospective Study for Laboratory Diagnosis of HHV8 Infection in Solid Organ Donors and Transplant Recipients and Evaluation of the Clinical Impact After Transplantation.

BACKGROUND: We performed serological and molecular pretransplant screening in solid organ transplant (SOT) donors and recipients in north central Italy and a surveillance program for human herpesvirus 8 (HHV8) infection after transplant, aiming to establish an optimal management of HHV8 infection in SOT recipients. METHODS: For pretransplant HHV8 screening in both donors and recipients, 6 serological (4 indirect immunofluorescent assays [IFA] and 2 enzyme-linked immunosorbent assays-both HHV8 lytic and latent antigen based) and 2 molecular assays were used. A reference standard to identify HHV8-positive patients was defined by at least 2 positive assays. All transplant patients at risk to develop HHV8-related disease underwent virological posttransplant monitoring by quantitative real-time polymerase chain reaction (PCR) assay. RESULTS: Human herpesvirus 8 seroprevalence was 4% (10/249) in donors and 18% (93/517) in organ recipients. The best performance was obtained by 2 lytic antigen-based IFAs that showed almost perfect agreement to the reference standard (0.943 and 0.931 Cohen kappa). Human herpesvirus 8-DNA was detected in 6.8% and 2.9% of HHV8-seropositive donor samples by in-house nested PCR and quantitative real-time PCR assays, respectively. After transplant, 3 (25%) of 12 HHV8-mismatch patients (seropositive donor/seronegative recipient) developed a primary infection, one of whom developed a lethal nonmalignant illness. Two of 93 HHV8-seropositive recipients (2.1%) had viral replication in posttransplant period, one of whom developed Kaposi sarcoma. CONCLUSIONS: Serological assays, specifically lytic IFAs, were the best methodological approach to identify HHV8-infected SOT donors and recipients. A very low incidence (1.9%) of posttransplant HHV8-related disease was observed.

Simultaneous bilateral laparoscopic adrenalectomy is safe for synchronous large adrenal tumors.

Laparoscopy is now considered the gold standard for treating benign monolateral adrenal lesions. We present the case of a patient affected by Cushing's syndrome due to large bilateral adrenal adenomas (7.5 cm) who underwent simultaneous laparoscopic bilateral adrenalectomy. An anterior, lateral transperitoneal approach was used. Operative time was 200 minutes, and blood loss was 200 mL. No intraoperative complications were encountered. The postoperative course was uneventful, and the patient was discharged after 3 days. Laparoscopic bilateral adrenalectomy is a safe, effective procedure when performed by experienced hands and may be an alternative treatment for large adrenal lesions.

Outcome, incidence, and timing of infectious complications in small bowel and multivisceral organ transplantation patients.

BACKGROUND: Infectious complications still represent a major cause of morbidity and mortality in patients with organ transplantation. In particular, small bowel or multivisceral transplantation is complicated to a greater extent than other grafts as a consequence of infectious complications including sepsis. METHODS: This prospective study assessed outcome, incidence, and timing of infections in sequential patients undergoing small bowel or multivisceral transplantation (SB/MVTx) performed at a university transplant center between January 2001 and October 2003. Nineteen patients underwent transplantation during this period, 13 of whom (68%) undergoing isolated SB and 6 (32%) MV grafts with or without liver. RESULTS: The median follow up was 524 days (interquartile range=252-730) with an overall 24.4 person/year of observation. Postoperative mortality rate was 0.1 death/person/year; all patients, except one who died intraoperatively, were alive 6 months postsurgery. There were 100 documented infections including: 59 bacterial (2.4 events/person/year), 35 viral (1.4 events/person/year) and 6 fungal (0.2 events/person/year). Patients developed at least one episode of bacterial infection in 94% of the cases, viral infection in 67%, and fungal infection in 28%. CONCLUSIONS: This cohort describes the very common and complex nature of infectious complications in this challenging group of transplantation patients. Larger cohorts are needed to specifically address infection risk factors and longer term outcomes.