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The aim of this review is to compare the outcomes of surgical repair versus watchful waiting in asymptomatic or minimally symptomatic inguinal hernias.Preferred reporting items for systematic reviews and meta-analyses guidelines were employed. We analysed primary outcomes: pain, quality of life, pain during daily activities and visual analogue scale (VAS that measures pain at rest and on movement) and secondary outcomes: postoperative complications and recurrence.Pain and quality of life were not comparable due to differences in the parameters used in different articles. Pain interfering with normal daily activity was evaluated in one study and appears more favourable in the post-repair group respect to the watchful waiting (WW) group (5.1% versus 2.2%). VAS, measured in one study, at 6 months was more favourable in the surgery group (37% versus 44%). After 12 months the outcome was better in the control group than in the repair group (28% versus 30%). Conversion rate of the patient cohorts from watchful waiting to elective surgery was between 35.03% and 57.8%. The meta-analysis did not find significant statistical differences in the two groups examined for postoperative complications [RR = 0.95, 95% CI (0.50, 1.80), P = 0.88], as for hernia recurrence [RR = 1.01, 95% CI (0.50, 2.02), P = 0.98].WW seems to be an acceptable option for the patient with asymptomatic or minimally symptomatic inguinal hernias. Delaying surgical repair until symptoms appear is safe. Acute hernia incarcerations are not particularly frequent. The incidence of chronic pain after the repair is high. Physicians must select patients carefully and explain to them the risks and benefits of surgery.

Carl Wernicke described the disease bearing his name in 1881 and reported three cases characterized by the presence of mental confusion, ataxia, and ophthalmoplegia. Wernicke’s disease is mainly observed in alcoholic patients, due to decreased vitamin intake as a consequence of an unbalanced diet, and a reduction of absorption due to the effects of alcohol. Likewise, inadequate vitamin intake is prevalent in older patients. Wernicke’s encephalopathy due to inappropriate total parenteral nutrition (TPN) occurs infrequently; recently, there is an increase in the literature concerning Wernicke’s encephalopathy in patients after general and bariatric surgeries. We present two cases of Wernicke’s encephalopathy after oncologic gastrointestinal surgery by failure to administer vitamin B1 during TPN; to our knowledge, these are the first two cases of Wernicke’s encephalopathy after colorectal surgery for cancer. In our opinion, timely diagnosis and treatment are mandatory to avoid nonfunctional recovery and consequent malpractice legal actions as well as an increase in the health-care costs correlated with the prolonged hospital stay and with the nonfunctional recovery.

The use of meshes in inguinal hernia repair (IHR) has gained popularity but new complications have been observed. Mesh-related visceral complications (MRVCs) are generally considered rare and hence are not studied in depth. We carried out a thorough literature search and collected 101 clinical reports published from 1992 to 2018. The reported complications seem to have tripled in the last decade. Ninety-seven cases met the inclusion criteria and they were subdivided into four groups (group A-onlay IHR, group B-3-D IHR, group C-preperitoneal IHR, group D-laparoscopic IHR) to be analyzed, according to the herniorraphy technique. Every prosthetic IHR can be followed by MRVCs but, according to the present review, the highest incidence is related to laparoscopic repairs, the lowest to Lichtenstein technique. Time-to-event was shorter in case of preperitoneal position of the prosthesis than when the mesh was implanted over the transversalis fascia. Urinary bladder involvement predominantly occurred after laparosopic IHR. A pathogenic correlation between the most frequently complained clinical signs and the previous mesh herniorraphy was rarely reported. The diagnosis was generally made at laparotomy, which was usually performed as an emergency. Removing the infected mesh and resecting or suture repairing the involved viscera was the challenging surgical treatment. Prevention of MRVCs after inguinal hernia repair appears to be an important significant issue. It is important to pay attention to the choice of a proper implantation site, avoiding direct contact between the mesh and viscera, and to select a proper device.

In the last two decades, studies of lymphoscintigraphy imaging in lymphatic mapping reported an extreme heterogeneity of skin lymphatic drainage of some skin area, in contrast with the previous scientific literature. The aim of this study was to investigate the presence of any correlations between the topographical location of cutaneous melanoma and the topographical location of sentinel lymph nodes. Data from 165 patients undergoing sentinel lymph node biopsy between January 2013 and May 2021 were analyzed, demonstrating that melanomas in the Lumbar region presented a significant more heterogeneous drainage by site than those in the Scapular region (p < 0.01) and that melanomas in the Subscapular region were significantly more heterogeneous by laterality (unilateral vs. bilateral) than those in the Scapular region (p < 0.05). Results of this study supported the evidence of multiple lymphatic drainage as regards the sentinel node biopsy performed in skin melanoma located on the dorsal subscapular region and lumbar region. For this reason, the association of preoperative lymphoscintigraphy with another imaging evaluation is needed in these critical cutaneous areas. Recent technical developments enabling fluorescence lymphography together with indocyanine green have significantly improved the visualization of lymphatic drainage patterns at a microscopic level. In the preoperative phase, any doubt can be resolved by associating the SPET-CT scan to lymphoscintigraphy, while during the intraoperative phase, an additional evaluation with indocyanine green can be performed in doubtful cases. The aim of the duplex lymphatic mapping (pre and/or intraoperative) is an accurate search of sentinel nodes, in order to reduce the rate of false negatives.

ObjectiveThis study aimed to evaluate the incidence of chronic groin pain (primary outcome) and alterations of sensitivity (secondary outcome) after Lichtenstein inguinal hernia repair, comparing neurectomy with ilioinguinal nerve preservation surgery.Summary background dataThe exact cause of chronic groin postoperative pain after mesh inguinal hernia repair is usually unclear. Section of the ilioinguinal nerve (neurectomy) may reduce postoperative chronic pain.MethodsWe followed PRISMA guidelines to identify randomized studies reporting comparative outcomes of neurectomy versus ilioinguinal nerve preservation surgery during Lichtenstein hernia repairs. Studies were identified by searching in PubMed, Scopus, and Web of Science from April 2020. The protocol for this systematic review and meta-analysis was submitted and accepted from PROSPERO: CRD420201610.ResultsIn this systematic review and meta-analysis, 16 RCTs were included and 1550 patients were evaluated: 756 patients underwent neurectomy (neurectomy group) vs 794 patients underwent ilioinguinal nerve preservation surgery (nerve preservation group). All included studies analyzed Lichtenstein hernia repair. The majority of the new studies and data comes from a relatively narrow geographic region; other bias of this meta-analysis is the suitability of pooling data for many of these studies.A statistically significant percentage of patients with prosthetic inguinal hernia repair had reduced groin pain at 6 months after surgery at 8.94% (38/425) in the neurectomy group versus 25.11% (113/450) in the nerve preservation group [relative risk (RR) 0.39, 95% confidence interval (CI) 0.28–0.54; Z = 5.60 (P P = 0.08)]. At 12 months after surgery, there is no advantage of neurectomy over chronic groin pain; no significant differences were found in the 12-month postoperative groin pain rate at 9% (9/100) in the neurectomy group versus 17.85% (20/112) in the inguinal nerve preservation group [RR 0.50, 95% CI 0.24–1.05; Z = 1.83 (P = 0.07)]. One study (115 patients) reported data about paresthesia at 12 months after surgery (7.27%, 4/55 in neurectomy group vs. 5%, 3/60 in nerve preservation group) and results were not significantly different between the two groups [RR 1.45, 95% CI 0.34, 6.21;Z = 0.51 (P = 0.61)]. The subgroup analysis of the studies that identified the IIN showed a significant reduction of the 6th month evaluation of pain in both groups and confirmed the same trend in favor of neurectomy reported in the previous overall analysis: statistically significant reduction of pain 6 months after surgery at 3.79% (6/158) in the neurectomy group versus 14.6% (26/178) in the nerve preservation group [RR 0.28, 95% CI 0.13–0.63; Z = 3.10 (P = 0.002)].ConclusionIlioinguinal nerve identification in Lichtenstein inguinal hernia repair is the fundamental step to reduce or avoid postoperative pain. Prophylactic ilioinguinal nerve neurectomy seems to offer some advantages concerning pain in the first 6th month postoperative period, although it might be possible that the small number of cases contributed to the insignificancy regarding paresthesia and hypoesthesia.Nowadays, prudent surgeons should discuss with patients and their families the uncertain benefits and the potential risks of neurectomy before performing the hernioplasty.

Sentinel lymph node biopsy is fundamental in the staging of primary cutaneous melanoma (PCL), but reported lymphoscintigraphic patterns are very heterogeneous. In this systematic review, we evaluated the role of the popliteal station in below-knee PCL. A systematic search of literature through was conducted on the electronic databases PubMed, SCOPUS, and Web of Science (WOS) to identify eligible studies. A total of 22 studies (n=5673 patients) were included. During the analysis of the included articles, it was not possible to classify patients into the 3 Menes popliteal drainage pattern, obtained by lymphoscintigraphy. The analysis of lymphatic drainage in patients undergoing lymphoscintigraphy for melanoma of the lower extremities below the knee was reported in 5637 patients and the type of lymphatic popliteal drainage was reported only in 5.64% (320 patients). The rate of popliteal lymph nodes melanoma metastases was 1.49%: they were located exclusively at the popliteal level in 0.60%, at the popliteal and inguinal levels in 0.39%, at the popliteal and iliac level in 0.02%, and at the groin level in 0.48%. In conclusion, the most common lymphoscintigraphic pattern is represented by popliteal nodes in-transit or interval nodes, so metastases from below-knee melanomas commonly transit through popliteal nodes stations and arrive to inguinal nodes stations. The popliteal nodes are the primary station in about 5.64% of cases. Larger studies are needed to corroborate these findings.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The &ldquo, cytokine storm&rdquo, (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes. We retrospectively analyzed 31 patients admitted to Infectious Disease Department in &ldquo, St. Maria&rdquo, Hospital in Terni with confirmed SARS-CoV-2 infections, and analyzed the &ldquo, CS score&rdquo, (CSs) and the severity of COVID-19. Then we conducted a prospective study of COVID-19 patients admitted after the definition of the CSscore. This is the first study that proposes and applies a new score to quickly identify COVID-19 patients who are in a hyperinflammation stage, to rapidly treat them in order to reduce the risk of intubation. CSs can accurately identify COVID-19 patients in the early stages of a CS, to conduct timely, safe, and effect administration of immunomodulators, corticosteroids, and cytokine antagonists, to prevent progression and reduce mortality.

The Italian burden of disease associated with infections due to antibiotic-resistant bacteria has been very high, largely attributed to Carbapenem-Resistant Klebsiella pneumoniae (CR-Kp). The implementation of infection control measures and antimicrobial stewardship programs (ASP) has been shown to reduce healthcare-related infections caused by multidrug resistance (MDR) germs. Since 2016, in our teaching hospital of Terni, an ASP has been implemented in an intensive care unit (ICU) setting, with the &ldquo, daily-ICU round strategy&rdquo, and particular attention to infection control measures. We performed active surveillance for search patients colonized by Carbapenem-Resistant Enterobacteriaceae (CRE). In March 2020, coronavirus disease 2019 (COVID-19) arrived and the same ICU was reserved only for COVID-19 patients. In our retrospective observational study, we analyzed the bimonthly incidence of CRE colonization patients and the incidence of CRE acquisition in our ICU during the period of January 2019 to June 2020. In consideration of the great attention and training of all staff on infection control measures in the COVID-19 era, we would have expected a clear reduction in CRE acquisition, but this did not happen. In fact, the incidence of CRE acquisition went from 6.7% in 2019 to 50% in March&ndash, April 2020. We noted that 67% of patients that had been changed in posture with prone position were colonized by CRE, while only 37% of patients that had not been changed in posture were colonized by CRE. In our opinion, the high intensity of care, the prone position requiring 4&ndash, 5 healthcare workers (HCWs), equipped with personal protective equipment (PPE) in a high risk area, with extended and prolonged contact with the patient, and the presence of 32 new HCWs from other departments and without work experience in the ICU setting, contributed to the spread of CR-Kp in our ICU, determining an increase in CRE acquisition colonization.

BackgroundNerve identification is recommended in inguinal hernia repair to reduce or avoid postoperative pain. The aim of this prospective observational study was to identify nerve prevalence and find a correlation between neuroanatomy and chronic neuropathic postoperative inguinal pain (CPIP) after 6 months.MaterialA total of 115 patients, who underwent inguinal hernia mesh repair (Lichtenstein tension-free mesh repair) between July 2018 and January 2019, were included in this prospective observational study. The mean age and BMI respectively resulted 64 years and 25.8 with minimal inverse distribution of BMI with respect to age. Most of the hernias were direct (59.1%) and of medium dimension (47.8%). Furthermore, these patients were undergoing Dermatome Mapping Test in preoperatively and postoperatively 6 months evaluation.ResultsIdentification rates of the iliohypogastric (IH), ilioinguinal (II) and genitofemoral (GF) nerves were 72.2%, 82.6% and 48.7% respectively. In the analysis of nerve prevalence according to BMI, the IH was statistically significant higher in patients with BMI ConclusionThe anatomy of inguinal nerve is very heterogeneous and for this reason an accurate knowledge of these variations is needed during the open mesh repair of inguinal hernias. The new results of our analysis is the statistically significant higher IH nerve prevalence in patients with BMI

Surgical site infections (SSIs) are the most common healthcare-associated infections. The appropriate use of Surgical Antibiotic Prophylaxis (SAP) is a key component to reduce SSIs, while its inappropriate application is a major cause of some emerging infections and selects for antibiotic resistance. We describe an Antimicrobial Stewardship (AMS) intervention on SAP appropriateness. The prospective study was conducted in an Italian hospital, in 12 main surgical units, and was organized in three subsequent phases, as follows. Phase 0: Definition of hospital evidence-based guidelines and a new workflow to optimize the process of ordering, dispensing, administering and documenting the SAP. Phase 1: We analysed 2059 elective surgical cases from January to June 2018 for three SAP parameters of appropriateness: indication, choice and dose. Phase 2: In July 2018, an audit was performed to analyse the results, we reviewed 1781 elective surgical procedures from July to December 2018 looking for the same three SAP appropriateness parameters. The comparative analysis between phases 1 and 2 demonstrated that the correct indication, the correct dose and the overall compliance significantly improved (p-value 0.00128, p-value &lt, 2.2&middot, 1016 and p-value &lt, 5.6&middot, 1012 respectively). Our prospective study demonstrates a model of successful antimicrobial stewardship intervention that improves appropriateness on SAP.

Millions of abdominal wall repair procedures are performed each year for primary and incisional hernias both in the European Union and in the United States with extremely high costs. Synthetic meshes approved for augmenting abdominal wall repair provide adequate mechanical support but have significant drawbacks (seroma formation, adhesion to viscera, stiffness of abdominal wall, and infection). Biologic scaffolds (i.e., derived from naturally occurring materials) represent an alternative to synthetic surgical meshes and are less sensitive to infection. Among biologic scaffolds, extracellular matrix scaffolds promote stem/progenitor cell recruitment in models of tissue remodeling and, in the specific application of abdominal wall repair, have enough mechanical strength to support the repair. However, many concerns remain about the use of these scaffolds in the clinic due to their higher cost of production compared with synthetic meshes, despite having the same recurrence rate. The present review aims to highlight the pros and cons of using biologic scaffolds as surgical devices for abdominal wall repair and present possible improvements to widen their use in clinical practice.

The aim of this study is to evaluate the safety and efficacy of endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) after R1 endoscopic resection or local recurrence of early rectal cancer after operative endoscopy.Twenty patients with early rectal cancer were enrolled, including patients with incomplete endoscopic resection, or complete endoscopic resection of a tumor with unfavorable prognostic factors (group A, ten patients), and local recurrence after endoscopic removal (group B, ten patients). At admission, histology after endoscopic polypectomy was: TisR1(4), T1R0G3(1), T1R1(5) in group A, and TisR0(8), T1R0(2) in group B. All patients underwent ELRR by TEM with nucleotide-guided mesorectal excision (NGME).Mean operative time was 150 minutes. Complications occurred in two patients (10%). Definitive histology was: moderate dysplasia(4), pT0N0(3), pTisN0(5), pT1N0(6), pT2N0(2). Mean number of lymph-nodes was 3.1. Mean follow-up was 79.5 months. All patients are alive and disease-free.ELRR by TEM after R1 endoscopic resection of early rectal cancer or for local recurrence after operative endoscopy is safe and effective. It may be considered as a diagnostic procedure, as well as a curative treatment option, instead of a more invasive TME.

Central Mesh Failure (CMF) after abdominal wall repair (AWR) is uncommon but should be considered in case of recurrence. The mechanism is unclear and different theories are actually proposed, as the action of opposite forces acting in the abdominal wall on the prosthesis, and the characteristics of the device to be implanted. The use of lightweight meshes in some cases could be inadequate to withstand the bursting strenght of the abdominal wall. Three cases of incisional hernia recurrence due to central mesh failure are here reported. KEY WORDS: Abdominal wall repair (AWR), Central mesh failure (CMF), Hernia recurrence, Lightweight mesh.La rottura della protesi usata per la riparazione dei difetti della parete addominale è un evento poco comune che andrebbe, tuttavia, considerato tra le cause di recidiva. I meccanismi alla base di tale evento, che si verifica solitamente nella parte centrale della protesi, sono ancora poco chiari. Sono state proposte diverse teorie che considerano le forze antitetiche che agiscono sulla protesi impiantata nella parete addominale e le caratteristiche strutturali dei materiali impiantati. Protesi “leggere”, potrebbero essere insufficienti, in alcuni casi, a resistere alla tensione che si sviluppa a livello della parete addominale. In questo lavoro vengono presentati tre casi di ernia incisionale recidiva causata da una rottura centrale di protesi.

Aim of the present study is to propose a clinic-therapeutic course for the treatment of hemorrhoidal disease able to combine radical anatomic surgery with a painless postoperative path.The present study is based on the evaluation of 20 selected patients who underwent radical hemorrhoidectomy for very high grade hemorrhoidal disease. The clinical course was characterized by careful bowel cleansing, hemorrhoidectomy according to Milligan-Morgan using LigaSure, intraoperative perianal infiltration of Ropivacaine and postoperative use of analgesic drugs.A low postoperative pain may descend from a scheduled timing of clinical procedures. Preoperative bowel cleansing delays the first postoperative evacuation, thus avoiding the perianal nerve stimulation. The use of LigaSure allows to perform surgical excision in a perfect way: lack of hemostatic stitches, less tissue trauma, very low early morbidity. A rational and scheduled intra and postoperative drug administration offers a highly significant contribution to the pain control. The intra and postoperative use of drugs makes it possible to perform the so-called "preventive anesthesia with activation of the pain memory" and postoperative evacuations with low pain perception. All patients, in fact, reported low and well tolerated pain, satisfaction and return to normal activities in a short period.Radical hemorrhoidectomy with LigaSure and attention to pre, intra and postoperative protocol makes the procedure painless, safe and with low morbidity.Hemorrhoidectomy, LigaSure, Painless procedure.Gli autori propongono una procedura clinica, che consente di praticare un intervento anatomico di emorroidectomia radicale ben sopportato dal paziente, in funzione del dolore molto contenuto nel periodo post operatorio. Come è noto, negli interventi di emorroidectomia, in tutte le tecniche chirurgiche praticate, il dolore è legato alla complessità dell’intervento e, quindi, allo stadio di malattia. Per tale motivo abbiamo valutato nel nostro studio, i risultati relativi ad un gruppo selezionato di 20 pazienti con malattia emorroidaria avanzata ed sintomatica. Il protocollo clinico è stato caratterizzato da: accurata pulizia dell’intestino, emorroidectomia sec. Milligan- Morgan eseguita con LigaSure, infiltrazione intraoperatoria di Ropivacaina, uso postoperatorio di farmaci analgesici. La pulizia preoperatoria del colon, con assenza di evacuazione postoperatoria nelle successive 24-30 ore, evita in tale periodo una stimolazione nervosa perianale. L’uso del LigaSure consente di eseguire l’intervento in maniera ottimale: assenza di punti aggiuntivi per l’emostasi, minore trauma dei tessuti, morbilità immediata praticamente assente. Una programmata e razionale utilizzazione di farmaci in sede intra e postoperatoria permette un efficace controllo del dolore. L’uso di farmaci intraoperatori consente, inoltre, di attuare la “analgesia preventiva con attivazione della memoria del dolore” (paziente asintomatico sino alla prima evacuazione), mentre la somministrazione post operatoria permette di avere evacuazioni intestinali con bassa percezione del dolore. Applicando il protocollo descritto, abbiamo ottenuto, nei 20 casi selezionati, i seguenti risultati: tempo operatorio contenuto, assenza di sanguinamento intra e postoperatorio, assenza di ano fibroso o stenosi nei controlli a distanza, ritenzione urinaria, nel 35% dei soggetti, transitoria e reversibile (una singola cateterizzazione), dolore postoperatorio contenuto e ben tollerato in tutti i pazienti, rapido ritorno alla normale attività e vita di relazione, con buona soddisfazione dei pazienti.

In selected patients with N0 rectal cancer, endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) may be an alternative treatment option to laparoscopic total mesorectal excision (LTME). Aim of this study is to evaluate the short- and medium-term quality of life (QoL) from a retrospective analysis of prospectively collected data in patients with iT2–iT3 N0-N+ rectal cancer, who underwent ELRR by TEM or LTME after neoadjuvant radio-chemotherapy (n-RCT). Thirty patients with iT2–iT3 rectal cancer who underwent ELRR by TEM (n = 15) or LTME (n = 15) were enrolled in this study. The choice for one operation or the other was made on the basis of predefined criteria. QoL was evaluated by EORTC QLQ-C30 and QLQ-CR38 questionnaires at admission, after n-RCT and 1, 6, and 12 months after surgery. No statistically significant differences in QoL evaluation were observed between the two groups, both at admission and after n-RCT. At 1 month after surgery, significantly better results in the ELRR group were observed by QLQ-C30 in: Nausea/Vomiting (p = 0.05), Appetite Loss (p = 0.003), Constipation (p = 0.05), and by QLQ-CR38 in: Body Image (p = 0.05), Sexual Functioning (p = 0.03), Future Perspective (p = 0.05) and Weight Loss (p = 0.036). At 6 months after surgery, a statistically significant worse impact after LTME was observed by QLQ-C30 in: Global Health Status (p = 0.05), Emotional Functioning (p = 0.021), Dyspnea (p = 0.008), Insomnia (p = 0.012), Appetite Loss (p = 0.014) and by QLQ-CR38 in Body Image (p = 0.05) and Defecation Problems (p = 0.001). At 1 year, the two groups were homogenous as assessed by QLQ-C30, whereas the QLQ-CR38 still showed better results of ELRR versus LTME in Body Image (p = 0.006), Defecation Problems (p = 0.01), and Weight Loss (p = 0.005). Based on the present series, in selected patients, earlier restoration of patients’ functions is observed after ELRR by TEM than after LTME.

In the last decade new immunosuppression strategies have been developed, with the introduction of new pharmacological agents that act on different stages of the cell cycle (including for example sirolimus and brequinar). Nevertheless, in transplantation management there are still many controversies concerning medicolegal aspects. This article examines the Italian normative on transplantation, underlining the debate about the meaning of the term “brain death” as a description of the clinical condition of patients’ status as living or dead.

This investigation describes some morphological, age-related changes in different compartments and cells of the human thymus. Scanning electron microscopic observations were done on human thymus samples obtained from four young and eight elderly patients during thoracic surgery and/or diagnostic biopsy of the thymus, after receiving authorization from the Ethical Committee of our university. The morphological data were submitted to quantitative image analysis so as to obtain quantitative results. Subsequently, the related values were used for statistical analysis. Our findings demonstrate that (1) all thymus compartments (subcapsular spaces, cortical, medullar, thymus microenvironment) contain numerous thymocytes even after the thymus has aged. (2) In older humans, residual thymus lymphoid islets contain, in addition to fatty cells and/or fibrous cells, also the same types of resident and nonresident cells (permanent and moving cells) that are found in young and adult subjects. (3) Endothelial cells of thymus microvessels contain numerous gaps. These gaps are tight in young subjects and become loose with age. (4) Thymocytes, in older subjects, are always found near these loose endothelial gaps of thymus microvessels. (5) While thymus cortical microvessels are provided with pericytes and/or periarteriolar spaces, microvessels of the thymus medullar are free of such spaces. Our morphological and quantitative results lead us to consider the possibility that the thymus fraction of resident and permanent cells (including thymocytes and reticular epithelial cells) is larger in younger subjects compared with older ones. The endothelial loose gaps of thymus microvessels, in older subjects, can allow the bidirectional transit of thymocytes through the wall of the said microvessels. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc.

No religion formally forbid donation or receipt of organs or is against transplantation from living or deceased donors. Only some orthodox jews may have religious objections to "opting in." However, transplantation from deceased donors may be discouraged by Native Americans, Roma Gypsies, Confucians, Shintoists, and some Orthodox rabbis. Some South Asia Muslim ulemas (scholars) and muftis (jurists) oppose donation from human living and deceased donors because the human body is an "amanat" (trusteeship) from God and must not be desecrated following death, but they encourage xenotransplantation research. No religion formally obliges one to donate or refuse organs. No religion formally obliges one to consider cadaveric organs "a societal resource" or considers organ donation "a religious duty" (except some rabbis and isolated Muslim and Christian scholars) No religion has a formal position on "bonus points," which is priority on the waiting list. Living organ donation is strongly encouraged only between jesus christians (15 of 28 jesus christians worldwide have donated a kidney). No religion forbid this practice. Directed organ donation to people of the same religion has been proposed only by some Orthodox Jews and some Islamic Ulemas/Muftis. Only some Muslim Ulemas/Muftis and some Asian religions may prefer living donation over cadaveric donation. No religion prefers cadaveric over living donation. No religion formally forbid non-heart-beating donors (nhbd) cadaveric donation or cross-over donation. Due to the sacrad of human life, the Catholic Church is against donation from anencephalic donors or after active euthanasia. No religion formally forbid xenotransplantation. Addressing the participants of the First International Congress of the Society for Organ Sharing in 1991, Pope John Paul II said "There are many questions of an ethical, legal and social nature which need to be more deeply investigated. There are even shameful abuses which call for determined action on the part of medical association and donor societies, and especially of competent legislative bodies" and later on "In effect, the human body is always a personal body, the body of a person. The body cannot be treated as a merely physical or biological entity, nor can its organs and tissues ever be used as item for sale or exchange". Addressing the participants at the XVIII International Congress of the Transplantation Society in 2000, Pope John Paul II said "Accordingly, any procedure which tends to commercialize human organs or to consider them as items of exchange or trade must be considered morally unacceptable, because to use the body as an object is to violate the dignity of the human person" and later on added "The criteria for assigning donated organs should in no way be discriminatory (i.e. based on age, sex, race, religion, social standing, etc.) or utilitarian (i.e. based on work capacity, social usefulness, etc.)." To conclude, according to the Catechism of the Catholic Church Compendium signed by Pope Benedict XVI on june 28, 2005, 476. Are allowed transplantation and organ donation, before and after death? Organ transplantation is morally acceptable with the consent of the donor and without excessive risks for him/her. For the noble act of organ donation after death, the real death of the donor must be fully ascertained.

A questionnaire concerning informed recipient's consent for "extended criteria liver donors"(ECD), after approval of the Institutional Review Board(IRB), was sent in different times by e-mail to members of 2 scientific societies, ELPAT (Ethical,Legal and Psychologic Aspects of Organ Transplantation) and ELITA (European Liver and Intestine Transplant Association)-ELTR(European Liver Transplant Registry.The results were published in different papers in Transplantation Proceedings.By comparing tables in the 2011 ELPAT and 2013 ELITA papers, in the most recent paper less Liver Transplant Centers(LTC) considered age as high as 80 years (p.002)and SGOT90 IU (p.02), or all criteria together (p.0001), as indicators of ECD.This may reflects the fact that more recently LTC have become less selective, due to the rising mortality in the increasing liver transplant waiting list. In all these studies we highlighted both a disparity of practice across centres and the relatively large contribution made by ECD livers to the transplantation effort.Therefore patients should receive all the required informations concerning the quality of the liver offered to them for transplantation, not only when they are enlisted, but also when the liver becomes available and is proposed to them. It is also possible to create a special waiting list of patients not accepting ECD, although this option could delay liver transplantation and consequently increase mortality.Un questionario riguardante il consenso informato del ricevente per i cosiddetti donatori marginali di fegato (“extended criteria donors”-ECD) è stato inviato, previa approvazione del Comitato Etico, via e-mail ai membri di 2 società scientifiche, ELPAT(Ethical,Legal and Psychologic Aspects of Organ Transplantation) ed ELITA (European Liver and Intestine Transplant Association)-ELTR(European Liver Transplant Registry). I risultati sono stati pubblicati in diversi lavori apparsi su Transplantation Proceedings. Analizzando statisticamente le tabelle negli articoli 2011 ELPAT e 2013 ELITA, nel lavoro più recente meno Centri Trapianto di fegato (LTC) hanno considerato l’età fino a 80 anni (p.002) e SGOT90 IU (p.02), o tutti i criteri insieme (p.0001), come indicatori di donatore marginale. Ciò potrebbe riflettere il fatto che nel tempo i LTC sono divenuti meno selettivi, a causa della crescente mortalità dei pazienti in lista di attesa. Considerando che in tutti i nostri studi abbiamo riscontrato un notevole ricorso agli ECD, è necessario che i pazienti ricevano tutte le informazioni che vogliano richiedere sia al momento dell’iscrizione in lista di attesa, sia quando il fegato di un donatore venga effettivamente loro proposto. E’ anche possibile creare una lista di attesa separata, per pazienti che non accettano ECD: tale scelta però ritarda in modo inevitabile il trapianto e quindi, potenzialmente, aumenta la mortalità in lista di attesa.

The European Liver and Intestine Transplant Association (ELITA) and the European Liver Transplant Registry (ELTR) coordinated the distribution to European liver transplantation centers of an electronic questionnaire, developed by the first author, concerning the definition of extended criteria liver donation (ECD) and the implication for informed consent of transplant recipients. Completed questionnaires were received from 35 centers. All centers accepted ECD liver donors. The criteria for defining a liver donor as ECD were as follows: steatosis in 33 centers (94%); age up to 80 years in 15 centers (43%); serum sodium >165 mmol/L in 25 centers (71%); intensive care unit (ICU) stay with ventilation longer than 7 days in 17 centers (48%); aspartate aminotransferase (AST) >90 U/L, in 6 centers (17%); body mass index (BMI) >30 in 19 centers (54%); alanine aminotransferase (ALT) >105 U/L in 8 centers (23%); serum bilirubin >3 mg/dL in 15 centers (43%); and all criteria together in 2 centers (6%). Thirty-one centers informed the transplantation candidate of the ECD status of the donor, 20 (65%) when the patient registered for transplantation, 1 (3%) when an ECD liver became available, and 10 centers (32%) on both occasions. Thirteen centers required the liver transplantation candidate to sign a special consent form. Twenty centers informed the potential recipient of the donor's serology. Only 6 centers informed the potential recipient of any high-risk behavior of the donor.

Background: The cholinergic nerve fibers of coronary arteries, capillaries and veins were studied in younger and older humans by staining of acetylcholinesterase and cholineacetyltransferase activities on autopsy samples of coronary vessels with the aim of investigating age-related changes. Methods: Samples of human coronary vessels were harvested and exposed to the enzymatic staining for acetylcholinesterase, immunohistochemical staining for cholineacetyltransferase and quantitative analysis of images. Morphometric values were subjected to statistical analysis of data. Results: Our results demonstrated that both acetylcholinesterase and cholineacetyltransferase are localized in the coronary vessels of younger and older humans. Staining of these two enzymes showed specific age-related changes. Structures resembling cholinergic nerve fibers were located in coronary vessels, in the extra-parenchymal (large caliber) and intraparenchymal (small caliber) branches (arteries and veins), organized in a plexus. Coronary arterioles of large caliber (diameter > 150 µm) were found to have many cholinergic nerve fibers. The quantitative analysis of images and the statistical analysis of the data demonstrated that the cholinergic neurotransmitters of coronary vessels (especially the extra-parenchymal branches of coronary arteries) strongly decrease with age. Conclusions: The age-related changes of cholinergic nerve supply of the human coronary vessels may play a role in the control of coronary circulation. Further studies are needed in order to draw definite conclusions concerning the nervous control of coronary circulation under normal and/or pathological conditions.

Background: The functions of the bronchus-associated lymphoid tissue (BALT) are under the control of the autonomic nervous system (sympathetic and parasympathetic nerve fibers). Objectives: The relationships between the adrenergic nerve fibers and β-adrenergic receptors were studied in the human BALT with the aim to demonstrate a probable neuromodulation. Methods: Morphological observations (staining with hematoxylin-eosin and scanning electron microscopy images) were carried out on samples of human BALT harvested during autopsies. Moreover, histochemical staining for norepinephrine (adrenaline = adrenergic nerve fibers) as well as for other catecholamines was performed. Finally, β-adrenergic receptors were stained by means of a β-blocking, radiolabeled drug (pindolol 125I). All our data were submitted to morphometric analysis (quantitative analysis of images and statistical analysis of data). Results: Our results provide direct evidence of the presence and distribution of catecholaminergic nerve fibers and related β-adrenergic receptors in BALT. β-Adrenergic receptors are present above all in the most richly innervated part of the BALT, and are, therefore, in close relationship with their related adrenergic nerve fibers. Conclusions: Studies on the distribution of adrenergicneurotransmitters and related β-adrenergic receptors in the human BALT are the first step for the demonstration of a probable neuromodulation of BALT.

The relationship between catecholaminergic nerve fibers and beta-adrenergic receptors in the heart and in the coronary vessels was studied in humans. Only living tissues, harvested from brain-dead heart donors, were used in this experiment. Morphological observations and histochemical staining for norepinephrine and other catecholamines were carried out and beta-adrenergic receptors were stained by means of a beta-blocking fluorescent drug. All morphological data underwent quantitative analysis of images and statistical evaluation. This study provided direct evidence for the distribution of catecholaminergic nerve fibers and of beta-adrenergic receptors in the myocardium and in the coronary arteries. Catecholaminergic nerve fibers are located in the periadventitial tissue, in the adventitia and in the transitional zone between the intima and media. The beta-adrenergic receptors are mainly located in the more innervated part of the heart and coronary arteries but there is a major, although incomplete, overlap with related catecholaminergic nerve fibers. Moreover, using specific substrates and/or inhibitors, two types of beta-adrenergic receptors, beta(1) and beta(2), were demonstrated. Owing to the scarcity of available material (we used only four hearts), and objective difficulties in enrolling other patients, we are at this moment unable to draw general conclusions.

The pharmacological characteristics and the microanatomical localization of dopamine D(2)-like receptors, or more correctly spiroperidol binding sites, in the rabbit pulmonary circulation were studied using combined marker binding and light microscopy autoradiography with [((3))H]-spiroperidol (spiperone) as marker. The marker was bound to the samples of the pulmonary artery in a manner consistent with the labelling of dopamine D(2)-like receptors with an equilibrium dissociation constant (K(d)) of about 2.4+/-0.07 nmol/l and a maximum density of binding sites of 65+/-4.5 fmol/mg tissue. Samples of bronchial artery show the same results as those of the pulmonary artery. In contrast, binding experiments made with samples of rabbit lung (capillary of the microcirculation), of pulmonary veins and/or of bronchial veins did not allow the evaluation of specific binding.Autoradiography, observed with light microscopy, showed the development of specific silver grains within the whole wall of extraparenchymal branches of the pulmonary artery and/or of the bronchial artery. Development of silver grains was inhibited by compounds active on the dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, and bromocriptine than to displacement by N-propyl-nor-apomorphine, quinpirole and clozapine suggests that the binding sites observed in extraparenchymal, large and medium-sized branches of the rabbit pulmonary and bronchial arteries belong, likely, to the dopamine D(2) receptor subtype. Quantitative analysis of images let us count the amount of these receptors in many samples of the pulmonary and/or bronchial arteries.

The only countries that have allowed financial incentives for organ donation are Iran since 1988, and later on, Singapore and Saudi Arabia. In Europe, and of course in Italy, financial incentives for donors are prohibited. The author has completed extensive research via the Internet (PubMed) of worldwide scientific literature on paid organ donation, also researching studies concerning public opinion on organ commercialism and "regulated markets". Italian transplant laws also have been reported and analyzed.

Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after 1 day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1α, IL-1β, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase drammatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules.

The organization known as ELPAT (Ethical, Legal and Psychological Aspects of Organ Transplantation) coordinated the distribution of an electronic questionnaire concerning the definition of extended criteria liver donation (ECD) and the implication for informed consent of transplant recipients to European liver transplant centers. Completed questionnaires were received from 30 centers in 13 countries. Twenty-eight centers accepted ECD liver donors. The criteria for defining a liver donor as ECD were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%); serum sodium levels higher than 165 mmol/L in 17 centers (60%); intensive care unit stay with ventilation longer than 7 days in 16 centers (57%); serum glutamic oxalo-acitic transaminase levels higher than 90 U/L in 12 centers (42%); body mass indeces more than 30 in 10 centers (35%); serum glutamic pyruvic transaminase levels higher than 105 U/L in 10 centers (35%); serum bilirubin levels higher than 3 mg/dL in 10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers informed the transplant candidate of the ECD status of the donor: 10 centers (43%) when the patient registered for transplantation, 3 centers (14%) when an ECD liver became available, and 10 centers (43%) on both occasions. Ten centers required the liver transplant candidate to sign a special consent form. Ten centers informed the potential recipient of the donor's serology. Only three centers informed the potential recipient of any high risk behavior of the donor.

Financial incentives for organ donation (from living or brain-dead donors) have been considered ethically acceptable by some authors and have been accepted locally in some countries. In the United States of America, eight federal proposals have been rejected, while some kind of incentives have been approved at a local or state level. There is still a widespread concern that the acceptance of economic incentives could bring a commodification of the human body, constituting a "slippery slope" toward organ commercialism.

The present study first time detected D1-D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues, and revealed distribution features of dopamine receptor subtypes in the epicardium, myocardium, and endocardium. Samples from four native hearts coming from young brain-dead donors, which for technical reason were not used for transplants, were studied. Dopamine receptors were revealed by immunochemistry technique and immunoblot analysis. Morphometrical quantification of the density of each receptor subtype was performed by an image analyzer. Our results demonstrate that only four subtypes of dopamine receptors can be found in cardiac tissues: D1, D2, D4, and D5. These dopamine receptors have been detected in endocardium, myocardium, and epicardium. D1 receptors were stored primarily in the epicardial layer. Dopamine receptors are distributed in the wall of both atria and ventricles, and its transmural gradient can be described in the wall of the human heart. Sections of atria and ventricles exposed to antidopamine receptor antibodies showed fluorescent-positive reaction in the epicardium, myocardium and endocardium. D4 receptor immune reactivity was remarkably less intense than D2 receptor immune reactivity. All the subtypes of dopamine receptors are in close relationships with all cardiac structures. Our findings provide a favorable basis for researching the role of dopamine receptors in controlling functions of the human heart and in the pathogenesis of cardiovascular diseases.

Hepatocyte transplantation has been used for temporary metabolic support of patients in end-stage liver failure awaiting whole organ transplantation as a method to support liver function and facilitate regeneration of the native liver in cases of fulminant hepatic failure and as a "cellular therapy" for patients with genetic defects in vital liver functions. The aim of this paper was to discuss the basic research that led to clinical hepatocyte transplantation, the published clinical experience with this experimental technique, and some possible future uses of hepatocyte transplantation.

Background: Age-related changes of catecholaminergic nerve fibers supplying the myocardium and the coronary vessels were studied in adult and in old rats. Objective: The purpose of this study was to investigate whether there are quantitative changes in myocardial and/or coronary catecholaminergic nerve fibers and related neurotransmitters. Methods: Samples of myocardium and/or coronary vessels were studied by means of glyoxylic acid induced fluorescence, aldehyde-induced fluorescence, and neuropeptide Y immunoreactivity. All morphological results were submitted to quantitative analysis of images. Biochemical dosage of proteins and of norepinephrine was also performed, and morphological data were compared with biochemical ones. Finally, all data were subjected to statistical analysis. Results: Our findings are indicative of an age-related decrease of all types of fluorescent sympathetic nerve fibers in rat heart and coronary arteries. Moreover, our data show that aging induces a strong decrease of norepinephrine levels in tissue homogenates of rat heart and coronary vessels. The majority of the catecholaminergic nerve fibers that show strong age-related changes are not contiguous with contractile cells of myocardium and/or of vascular wall. In fact, these fibers are located in adventitial (or epicardial) and in endothelial (or endocardial) layers. Conclusion: The decrease of the catecholaminergic innervation of heart and coronary vessels of old rats can be in close relationships to the poor cardiac and/or coronary functions observed in old animals.

Our study population consisted of 402 Living Related Donors (LRD)--of which 344 pairs shared 1 haplotype (Group A) and of 209 Living Unrelated Donors (LURD) (Group B): 175 between spouse pairs (Group C)--132 from wife to husband (Group C1) and 43 from husband to wife (Group C2) as well as 32 between relatives in law or emotionally related patients and 2 between members of clergy (Group D). 199 pairs showed 3-6 HLA A B Dr mismatches (MM) with the donor and in 10 cases 0-2 MM. Donor and recipient mean age was 49 +/- 13.4 and 29 +/- 10.3 in Group A and respectively 46 +/- 11.2 and 48 +/- 9.6 in Group B. The post-transplant immunosuppression therapy was based on Cyclosporin A (CsA). Chi2 test was used to assess statistical significance. Donor mortality was 0%; perioperative morbidity was 15.2%. Graft function immediately started after surgery. The actuarial 1 yr, 5 yrs, 10 yrs and 15 yrs graft survival was in Group A: 94%, 86%, 84%, 75% vs. Group B: 89%, 78%, 71%, 70% (NS), Group C1: 90%, 75%, 67%, 69% vs. Group C2: 81%, 74%, 72%, 62% (NS) and Group C: 88%, 78%, 66%, 60% vs. Group D: 91%, 80%, 71%, 61% (NS). There was no statistically significant difference between LURD and LRD as far as graft survival. In conclusion, we certainly agree with the guidelines issued by the International Congress on Ethics in Organ Transplantation (Munich, December 10-13,2002): kidney transplantation from living donors is a safe and effective procedure and should not be discouraged.

ELPAT (Ethical, Legal, and Psychologic Aspects of Organ Transplantation) coordinated the distribution to European liver transplant centers of an electronic questionnaire regarding the definition of extended-criteria liver donation (ECD) and its implication for informed consent by transplant recipients. Completed questionnaires were received from 30 centers in 13 countries including 28 who accepted ECD liver donors. The criteria to define a liver donor as ECD were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%); serum sodium >165 mmol/L in 17 centers (60%); ICU stay with ventilation >7 days in 16 centers (57%); serum glutamic oxaloacetic transaminas >90 U/L, in 12 centres (42%); body mass index >30 kg/m 2 in 10 centers (35%); serum glutamate pyruvate transaminase >105 U/L in 10 centers (35%); serum bilirubin >3 mg/dL in 10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers informed the transplant candidate of the ECD status of the donor: 10 (43%) when the patient registered for transplantation, 3 (14%) when an ECD liver became available, and 10 (43%) on both occasions. Ten centers required the liver transplant candidate to sign a special consent form. Ten centers informed the potential recipient of the donor's serology. Only 3 centers informed the potential recipient of any high-risk behavior of the donor.

The use of living donors, particularly if unrelated, in kidney transplantation is still not recommended although many transplant cen- ters have come to accept the procedure. Usually the main argument against this approach is ethical. Acknowledging this problem, we accept biologically unrelated donors only if they have an emotional closeness to the recipient. From November 1982 to November 1997, 527 kidney allo- grafts from living donors were performed at our institution. Of these 302 living donors were first-degree relatives of the recipient and shared one haplotype (LRD) and 172 were unrelated (LURD). Among the LURD group 146 donors were "emotionally related"—wife to husband 110 cases and husband to wife 35 cases and 1 case from a nun to a friar. Statistical analysis of the results was performed with the 2 method. Actuarial graft survival rates in the LRD and LURD groups were 91% and 87% at 1 year, 77% and 79% at 5 years, and 66% and 69% at 9 years (p n.s.). In conclusion kidney transplantation between unrelated donors and recipi- ents may be a valid alternative in view of the cadaver organ shortage. It is a procedure that can be performed successfully and that provides a "gift of life" for both the patient and the family. Since the beginning of kidney transplantation the use of living related donors (LRD) has been a regular and accepted phenom- enon in both the United States and Europe. Meanwhile, as kidney transplant programs became established and began to expand, the proportion of living donor transplants decreased, also as a conse- quence of the poor results obtained under conventional therapy. With the increasing availability of dialysis, most centers discour- aged transplantation from living donors, given that a cadaveric kidney provides an equal benefit to the recipient. The introduction of cyclosporine led to significant improvement in the results of cadaveric organ transplantation. This improve- ment, together with a dramatic growth in the number of patients on the waiting list because of the inadequate supply of cadaver kidneys, prompted renewed expansion of the criteria for accept- able living donors. The validity of kidney transplant from living donors (LD) is based on many ethical and clinical considerations, among them the free will of the donor, limits to the risks to donor's health, and the results, which in most reports are better than with cadaver donor (CD) kidney transplantation. The use of living unrelated donors (LURD) in kidney transplantation is highly debated; in the United States it accounts for only 2% of all kidney transplants performed yearly. Among the unrelated donors, those who are emotionally re- lated are more frequently preferred. In this category the major group is represented by spouses, and a minor number can be recruited among acquired relatives such as in-laws.

TRANSPLANTATON has been the choice option to treat successfully an increasing number of acute and chronic human pathologies with declining morbidity and mortality. However, availability of organs from human donors is limited and dramatically inadequate with respect to patient requests. Xenotransplantation from large-sized mammals has thus been reconsidered as a tool to overcome the present unbalance between organ offers and requests. Pigs have been chosen because they can be easily and cheaply bred; they do not raise ethical questions—their use as alimentary resources is generally admitted; and they possess organs largely human compatible for size, anatomical organization, and physiology. Nevertheless, this option is usually compromised by the occurrence of an irreversible hyperacute vascular rejection of the animal transplanted organ as soon as it is perfused with human blood, mediated by natural preformed antibodies and by the activation of the complement cascade. Downregulating the complement system by expressing on the surface of the swine organs one or more species-specific negative modulators of the complement complexes, such as human decay accelerating factor (hDAF), could prevent the rejection of the graft. Our group has obtained a number of transgenic pigs for hDAF using sperm-mediated gene transfer (SMGT), an innovative and highly efficient and reproducible method. In SMGT, spermatozoa are employed as natural vectors of foreign DNA and are bound, captured, and internalized into recipient egg cells to generate a genetically modified progeny. Revealing the expression of the protein on the surface of the organs is an important confirmation for successful transgenesis. The aim of this report is to show, by immunohistochemical detection, the expression of hDAF in transgenic hearts, organs maximally eligible for xenotransplantation.