Mesenteric Cyst with GI Symptoms: A Fluid Approach to Treatment-Case Report and Literature Review.

Mesenteric cysts are defined as a heterogeneous group of intra-abdominal cystic lesions of the mesentery or omentum that may be found in any portion of the gastrointestinal tract from the duodenum to the rectum. The clinical condition is entirely asymptomatic in many patients, particularly with small cysts. The diagnosis is typically incidental and secondary to imaging performed for other purposes. In symptomatic patients, the clinical picture is characterized by nonspecific gastrointestinal signs and symptoms. Treatment may be surgical or via interventional radiology. We report the case of a 55-year-old female patient complaining of left-sided abdominal discomfort and constipation lasting three months. An abdominal ultrasound showed the presence of a 10 × 14 × 16 cm anechoic cystic mass filling the whole anterior and left abdominal cavity, confirmed by CT and MRI. The cyst, removed laparoscopically, was histologically a simple mesothelial cyst. We reviewed the international literature over the last 10 years of all cases with mesenteric cysts > 10 cm in evaluating gastrointestinal symptoms at diagnosis, histology, performed treatment, and outcome.

Brain death in pregnancy: a systematic review focusing on perinatal outcomes.

OBJECTIVE: Brain death (BD) during pregnancy might justify in select cases maternal somatic support to obtain fetal viability and maximize perinatal outcome. This study is a systematic review of the literature on cases of brain death in pregnancy with attempt to prolong pregnancy to assess perinatal outcomes. DATA SOURCES: We performed a systematic review of the literature using Ovid MEDLINE, Scopus, PubMed (including Cochrane database), and CINHAIL from inception to April 2020. STUDY ELIGIBILITY CRITERIA: Relevant articles describing any case report of maternal brain death were identified from the aforementioned databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described at least 1 case of maternal brain death. METHODS: Only cases of brain death in pregnancy with maternal somatic support aimed at maximizing perinatal outcome were included. Maternal management strategy, diagnosis, clinical course, fetal monitoring, delivery, and fetal and neonatal outcome data were collected. Mean, range, standard deviation, and percentage calculations were used as applicable. RESULTS: After exclusion, 35 cases of brain death in pregnancy were analyzed. The mean gestational age at diagnosis of brain death was at 20.2±5.3 weeks, and most cases (68%) were associated with maternal intracranial hemorrhage, subarachnoid hemorrhage, and hematoma. The most common maternal complications during the study were infections (69%) (eg, pneumonia, urinary tract infection, sepsis), circulatory instability (63%), diabetes insipidus (56%), thermal variability (41%), and panhypopituitarism (34%). The most common indications for delivery were maternal cardiocirculatory instability (38%) and nonreassuring fetal testing (35%). The mean gestational age at delivery was 27.2±4.7 weeks and differed depending on the gestational age at diagnosis of brain death. Most deliveries (89%) were via cesarean delivery. There were 8 cases (23%) of intrauterine fetal demise in the second trimester of pregnancy (14-25 weeks), and 27 neonates (77%) were born alive. Of the 35 cases of brain in pregnancy, 8 neonates (23%) were described as "healthy" at birth, 15 neonates (43%) had normal longer-term follow-up (>1 month to 8 years; mean, 20.3 months), 2 neonates (6%) had neurologic sequelae (born at 23 and 24 weeks of gestation), and 2 neonates (6%) died (born at 25 and 27 weeks of gestation). Mean birth weight was 1,229 grams, and small for gestational age was present in 17% of neonates. The rate of live birth differed by gestational age at diagnosis of brain death: 50% at <14 weeks, 54.5% at 14 to 19 6/7 weeks, 91.7% at 20 to 23 6/7 weeks, 100% at 24 to 27 6/7 weeks, and 100% at 28 to 31 6/7 weeks. CONCLUSION: In 35 cases of brain death in pregnancy at a mean gestation age of 20 weeks, maternal somatic support aimed at maximizing perinatal outcome lasted for about 7 weeks, with 77% of neonates being born alive and 85% of these infants having a normal outcome at 20 months of life. The data of this study will be helpful in counseling families and practitioners faced with such rare and complex cases.

Chronic Rejection After Intestinal Transplant: Where Are We in Order to Avert It?

Chronic rejection affects the long-term survival of all solid organ transplants and, among intestinal allografts, occurs in up to 10% of the recipients. The insidious clinical evolution of the chronic allograft enteropathy, the absence of noninvasive biomarkers, and the late endoscopic findings delay its diagnosis. No pharmacological approach has been proven effective, and allograft removal nowadays still represents the only available therapy. The inclusion of the liver in the visceral allograft appears to be the only intervention affecting the development of chronic rejection, as revealed by large-center studies and registry reports. A significant body of evidence emerged from the experimental setting and provided essential knowledge on the complex mechanisms behind the development of chronic allograft enteropathy. More recently, donor-specific antibodies have been suggested as an early, key element in the natural history of chronic allograft enteropathy and several novel approaches, tackling the antibody-mediated graft injury, have gained acceptance in clinical settings and are believed to impact on chronic rejection. The inclusion of a liver allograft is advocated when re-transplanting a sensitized recipient, due to its protective effect against humoral immunity. Multicenter trials are required to understand and tackle chronic rejection, and find the therapeutic answer to this clinical dilemma.

Pre-emptive Intestinal Transplant: The Surgeon's Point of View.

Pre-emptive transplantation is a well-established practice for certain types of end-organ failure such as in the use of kidney transplantation. For irreversible intestinal failure, total parenteral nutrition (TPN) remains the gold standard, due to the suboptimal long-term results of intestinal transplantation. As such, the only role for pre-emptive transplantation, if at all, will be for patients identified to be at high risk of complications and mortality while on definitive long-term TPN. In these patients, the timing of early listing and transplantation could become life-saving, taking into account that mortality on the waiting list is still the highest for intestinal candidates. The development of simulation models or pre-transplant scoring systems could help in selecting patients based on potential outcome on TPN or with transplantation, and recent reports from high-volume centers identify few underlying pathologic conditions and some TPN complications as at higher risk of increased morbidity and mortality. A pre-emptive transplant could be used as a rehabilitative procedure in a well-selected case-by-case scenario, among TPN patients at risk of liver failure, repeated central line infections, mesenteric infarction, short bowel syndrome (SBS) <50 cm or with end stoma, congenital mucosal disease, desmoid tumors: These conditions must be carefully evaluated, not to underestimate the clinical stage nor to over-estimate the impact of a temporary situation. At the present time, diseases with a variable and unpredictable course, such as intestinal dysmotility disorders, or quality of life and financial issues are still far from being considered as indications for a pre-emptive transplant.

Advances in allograft monitoring after intestinal transplantation.

PURPOSE OF REVIEW: The intestinal allograft, with an enormous lymphoid load, is a highly immunogenic organ which elicits a strong alloimmune response. In the early posttransplant period, a robust graft biopsy protocol via a temporary ileostomy is utilized for surveillance to detect rejection. In the later posttransplant period, after enteral continuity is reestablished, graft biopsies via a colonoscopy become more cumbersome. Alternative methods for intestinal allograft monitoring other than graft biopsy are of particular interest. RECENT FINDINGS: Biomarkers and diagnostic tools, such as granzyme B, perforin, fecal calprotectin, citrulline, donor-specific antibody, and zoom video endoscopy have all been studied for application as reliable methods of performing intestinal allograft surveillance. Each modality has the capability to monitor a separate and unique process in the host-allograft immune response. SUMMARY: The goal to find a reliable, reproducible, and noninvasive method for intestinal graft monitoring remains an elusive one. Many of the current modalities available only serve to act as complementary tests in conjunction with astute clinical observations. Graft biopsy remains the gold standard for monitoring the intestinal allograft.

A commentary on iPS cells: potential applications in autologous transplantation, study of illnesses and drug screening.

Undoubtedly, the focus of the field of stem cell research is predominantly aimed at the artificial reprogramming of human somatic cells for the production of induced pluripotent stem (iPS) cells. This relatively new technology may circumvent the ethical issues of using human embryonic stem (hES) cells for the potential applications in cell replacement therapy. Besides such ethical issues, iPS cell technology offers the advantage of obtaining patient-derived tissues and/or cells, which may be utilized for autologous transplantation and tissue regeneration, investigation of a variety of human illnesses and for the screening of new drugs. The field of stem cell research has placed a major emphasis in understanding the genetic and epigenetic codes for pluripotency, in order to control and optimize autologous transplantation techniques and avoid teratoma formation.

The state of research in Europe and in Italy: the risks of short-sighted decisions.

Research is facing declining funding rates everywhere, affecting the cultural and economic growth of some of major world powers. We looked at the choices on funding allocation made by the USA and by Europe, to compare priorities and analyze consequences. Also, within Europe, we focused on Italy and on its consistent brain-drain phenomenon, as an example of short-sighted research policies that appear to require not only the urgent infusion of monetary resources and the creation of new job opportunities, but also and especially a general change of cultural approach.

Completely steroid-free immunosuppression in liver transplantation: a randomized study.

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT. METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and six months post-OLT. Protocol liver biopsies were performed at OLT, 2 and 24 wk post-OLT or when indicated. RESULTS: Rejection occurred in two patients. Patient survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (80% vs. 63%) post-OLT were similar between CS and CS-free group, respectively. Death-censored graft survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (75% vs. 63%) were also similar. The risk of new-onset DM, hypertension, hypercholesterolemia, and weight gain was similar between groups. CONCLUSION: CS avoidance with basiliximab, calcineurin inhibitor, and EC-MPS is safe and effective as CS- containing immunosuppression in adult OLT.

A Hypothetical New Challenging Use for Indocyanine Green Fluorescence during Laparoscopic Appendectomy: A Mini-Series of Our Experience and Literary Review.

Laparoscopic appendectomy (LA) is a well-standardized surgical procedure, but there are still controversies about the different devices to be used for the appendiceal stump closure and the related postoperative complications. Indocyanine green (ICG) fluorescence angiography (FA) has already been shown to be helpful in elective and emergency surgery, providing intraoperative information on tissue and organ perfusion, thus guiding the surgical decisions and the technical strategies. According to these two aspects, we report a mini-series of the first five patients affected by gangrenous and flegmonous acute appendicitis intraoperatively evaluated with ICG-FA during LA. The patients were admitted to the Emergency Department with an usual range of symptoms for acute appendicitis. The patients were successfully managed by fully LA with the help of a new hypothetical challenging use of ICG-FA.

Autocrine IGF-II-Associated Cancers: From a Rare Paraneoplastic Event to a Hallmark in Malignancy.

The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging in the last few decades, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IRA) content, with (b) an increase in IGF-II high-molecular weight cancer-variants (big-IGF-II), and (c) a stage-progressive increase in the IGF-II autocrine signal in the cancer cell, mostly during the transition from benign to malignant growth. An increasing and still under-exploited combinatorial pattern of the IGF-II signal in cancer is shaping up in the literature with respect to its transducing receptorial system and effector intracellular network. Interestingly, while surgical and clinical reports have traditionally restricted IGF-II secretion to a small number of solid malignancies displaying paraneoplastic hypoglycemia, a retrospective literature analysis, along with publicly available expression data from patient-derived cancer cell lines conveyed in the present perspective, clearly suggests that IGF-II expression in cancer is a much more common event, especially in overt malignancy. These findings strengthen the view that (1) IGF-II expression/secretion in solid tumor-derived cancer cell lines and tissues is a broader and more common event compared to the reported IGF-II association to paraneoplastic hypoglycemia, and (2) IGF-II associates to the commonly observed autocrine loops in cancer cells while IGF-I cancer-promoting effects may be linked to its paracrine effects in the tumor microenvironment. Based on these evidence-centered considerations, making the autocrine IGF-II loop a hallmark for malignant cancer growth, we here propose the functional name of IGF-II secreting tumors (IGF-IIsT) to overcome the view that IGF-II secretion and pro-tumorigenic actions affect only a clinical sub-group of rare tumors with associated hypoglycemic symptoms. The proposed scenario provides an updated logical frame towards biologically sound therapeutic strategies and personalized therapeutic interventions for currently unaccounted IGF-II-producing cancers.

The Risk of Malignant Degeneration of Müllerian Derivatives in PMDS: A Review of the Literature.

Persistent Müllerian Duct Syndrome (PMDS) is a rare autosomal recessive disorder of sex development characterized by the presence of fallopian tubes, uterus and upper one-third of the vagina in individuals with XY genotype and normal male phenotype. The main complications of PMDS are infertility and the rare risk of malignant degeneration of both testicular and Müllerian derivatives. We report the case of a 49-year-old man who, during repair of an incisional hernia, was incidentally found to have a uterine-like structure posterior to the bladder. In the past at the age of 18 months, he had undergone bilateral orchidopexies for bilateral cryptorchidism. The intraoperative decision was to preserve the uterine-like structure and make a more accurate diagnosis postoperatively. Evaluation revealed an XY chromosome and imaging consistent with PMDS. The patient was informed about the risk of neoplastic transformation of the residual Müller ducts and was offered surgical treatment, which he declined. Subsequent follow-up imaging studies, including testicular and pelvic ultrasound, were negative for findings suggestive of malignant testicular and Mullerian derivative degeneration. A review of the international literature showed that, when a decision is taken to remove the Mullerian derivatives, laparoscopy and especially robotic surgery allow for the successful removal of Müllerian derivatives. Whenever the removal of these structures is not possible or the patient refuses to undergo surgery, it is necessary to inform the patient of the need for adequate follow-up. Patients should undergo regular pelvic imaging examination and MRI might be a better method for that purpose.

Living Kidney Donor Transplantation and Global Kidney Exchange.

Global kidney exchange offers an opportunity to expand living donor kidney transplants internationally to patients with immunologic barriers. The concept has been proven to be successful in a limited number of transplants. However, a number of misconceptions have created obstacles to its development. We suggest that a systematic application of this innovative tool would offer opportunities to treat thousands of patients worldwide who are presently denied a transplant and often even access to dialysis.

Benign Hepatic Tumors and Liver Transplantation: A Literature Review.

Management of benign liver tumors represents still an open debate, with no clear guidelines for patient selection,treatment options, and indications to surgical intervention. Usually, most of these diseases are conservatively treated, in view of their low potential malignancy and incidental diagnosis. However, when the lesions are symptomatic, with a major hepatic parenchyma involvement or life-threatening complications, liver transplant represents the only curative option. The scope of this review is to present an up-to-date state of the art of transplantable benign hepatic neoplasms.

Pediatric Liver Transplantation: Long-Term Follow-Up Issues.

Pediatric liver transplant is an established life-saving procedure for children with end-stage liver diseases, achieving excellent graft and patient survival but with effects on quality of life and psychological welfare in the long-term. With the natural increase in the number of pediatric transplant patients becoming adults, it is essential to successfully plan and manage issues affecting late outcomes in the vulnerable pediatric transplant population. This study offers an overview of the long-term surgical complications, the consequences of immunosuppression (such as posttransplant diabetes, hypertension, cardiovascular disease, and renal dysfunction), and the infection and malignancy risks. Finally, because quality of life is now an inclusive measurement of patient satisfaction, guidance on how to facilitate the transition to adulthood, empowering transplant recipients, is also provided.

Insertional mutagenesis and development of malignancies induced by integrating gene delivery systems: implications for the design of safer gene-based interventions in patients.

Effective gene-based interventions for the treatment of genetic disorders, neurodegenerative diseases and cardiovascular maladies require longterm transgene expression in target cells. Integrating viral vector systems based on the genera of the retroviridae and on adeno-associated virus are suitable tools, as the integration of viral vector genomes into the cellular chromosomal DNA allows for a more stable and long-lasting transgene expression than episomal gene-delivery models. Two nonviral gene-delivery systems with integrating properties have also been developed. These are based on the Sleeping Beauty DNA transposon system and on the Streptomyces bacteriophage integrase phiC31. However, the integration of recombinant vector systems may damage the natural genetic arrangement of the target cell. Such genetic alterations are termed insertional mutagenesis, which might result in malignant cell transformation. Insertional mutagenesis caused leukemia in five patients who participated in clinical trials for the treatment of severe combined immunodeficiency (SCID)-X1; sadly, one of the patients died. Gene therapists had to assess the real risk-versus-benefit ratio for the use of retroviral vectors in patients and devise novel strategies to minimize the occurrence of insertional mutagenesis-related malignancies. In this respect, a particular emphasis was placed on the engineering of enhancer-less self-inactivating retroviridae-based systems.

Use of enteric-coated mycophenolate sodium in liver transplant patients with intestinal intolerance caused by mycophenolate mofetil.

BACKGROUND: Post-transplant gastrointestinal (GI) side effects can impair a patient's quality of life (QoL). This study investigates the improvement in GI side effects and related QoL changes in recipients of liver transplantation (OLT) after converting patients from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS). METHODS: Thirty-four patients who underwent OLT and suffered from GI intolerability were included in this study. Infectious causes of GI intolerability were excluded. QoL assessed by the Gastrointestinal Quality of Life Index was evaluated before conversion and at months 3, 6 and 12 post-conversion. All patients received baseline immunosuppression of one calcineurin inhibitor, MMF, with or without steroids. Patients were converted from MMF to EC-MPS on an equimolar basis. Paired t-test was used to assess differences in mean score changes over time. RESULTS: Conversion from MMF to EC-MPS for GI intolerability post-OLT shows statistically significant improvement in GI-related QoL at 3, 6, and 12 months when compared to baseline assessments (p < 0.05 for total mean score); nonetheless, one-third of patients discontinued EC-MPS. No rejection episodes, deaths or graft loss were seen during the study period. CONCLUSION: OLT recipients who develop GI side effects caused by MMF can be safely converted to EC-MPS with improvement to their QoL.