Diet and pancreatic cancer: many questions with few certainties.

UNLABELLED: BACKGROUND, OBJECTIVES: Pancreatic cancer ranks fourth for cancer mortality for men and women in the United States. This is a particularly devastating cancer since the case-fatality proportion approaches 90% within 12 months following diagnosis. Therefore, understanding the etiology and identifying the risk factors are essential for the primary prevention of this deadly disease. Of the few potentially modifiable risk factors that have been identified, cigarette smoking, history of diabetes mellitus, and obesity seem to be among the most consistent, but the effect of dietary factors is still unclear. The aim of our study is to review of the literature examining the potential role of carbohydrates, fatty acids, meat, fruit and vegetables, alcohol. DISCUSSION: Although large prospective cohort studies with questionnaire based analyses will continue to have much to offer in defining predisposing factors for difficult diseases, such as pancreatic cancer, unfortunately dietary questionnaires do not reflect the bioavailability of the nutrients from various foods, the level of absorption from the digestive tract, or individual differences in metabolism. CONCLUSIONS: Greater use of participant-derived biological samples, banked plasma, germline DNA, and tumour tissue samples may help to the understanding of pancreatic cancer pathogenesis.

Sexual dysfunction after elective endovascular or hand-assisted laparoscopic abdominal aneurysm repair.

OBJECTIVE: To evaluate the incidence of sexual dysfunction and retrograde ejaculation after elective endovascular aneurysm repair (EVAR) and hand-assisted laparoscopic surgery (HALS) for abdominal aortic aneurysm (AAA). METHODS: A total of 100 patients eligible for elective repair of infrarenal AAAs were randomised in two groups: EVAR and HALS. The quality of sexual function was evaluated using the International Index of Erectile Function (IIEF), a 15-item questionnaire. Patients completed the IIEF preoperatively and at 12 months. The incidence of retrograde ejaculation was also evaluated. RESULTS: One- and 12-month mortality rates were zero. Three patients in the EVAR group (6%) and two patients in the HALS group (4%) reported an erectile dysfunction (p = NS). The quality of sexual function at 1 year was similar in both groups: total score of 66 in the EVAR group versus 68 in the HALS group (p = 0.66). Retrograde ejaculation was detected in three cases in the HALS group versus no case in the EVAR group. CONCLUSIONS: The HALS technique could be a minimally invasive alternative for sexually active males unsuitable for EVAR repair.

Visceral leishmaniasis in the early post-transplant period after kidney transplantation: clinical features and therapeutic management.

Visceral leishmaniasis (VL) is a rare complication of kidney transplantation, with <100 cases reported in the literature. It is a life-threatening condition and usually occurs as a late complication after transplantation, with a median delay of 18 months between transplantation and onset of disease. We report the clinical features and management of 5 kidney transplant recipients who presented with VL in the early post-transplant period. All patients were successfully treated with liposomal amphotericin B (L-AMB), but 2 patients experienced graft loss. VL should be considered in the differential diagnosis in kidney transplant recipients living in endemic areas, who present with unexplained fever and pancytopenia in the early post-transplant period. Leishmania serology should be included in the screening of all transplant recipients, in order to identify a group of patients who could benefit from preemptive anti-Leishmania therapy. Therapy with L-AMB is highly effective and well tolerated in kidney transplant recipients with VL.

Differentiated thyroid cancer: role of the lymph node dissection.

Thyroid cancer is the most common endocrine malignancy with the highest mortality, so it has generated considerable debate and voluminous literature by endocrinologists, surgeons, and nuclear physicians. If total thyroidectomy is the primary treatment for patients with differentiated thyroid cancers (DTC) and it has proven to be effective and safe, the extent of lymph nodes dissection remains controversial among experts in the field. This controversy persists largely due to the lack of a prospective randomized controlled trial to define whether the addition of central lymph node dissection (CLND) to total thyroidectomy for papillary thyroid cancer (PTC) confers an increased risk of permanent hypoparathyroidism and permanent nerve injury. According to the Consensus Conference of the UEC's Club therapeutic modified radical neck dissection (MRND) should be performed only in the patients with evidence of neoplastic multiple lymph node involvement. Although central lymph node dissection may increase the risk of hypoparathyroidism and nerve injury when compared with total thyroidectomy without CLND, it may decrease recurrence of PTC and likely improves disease specific survival and offers a sufficient alternative to routine prophylactic modified radical neck dissection. Selective central lymph node dissection should be performed, under the care of experienced surgeons, in high risk patients (50 years or older aged, large tumor expansion within the thyroid, or with extrathyroid extension), with the extension to the station II-III-IV in case of single lymph node involvement.

Acute renal failure due to ureteral obstruction in a kidney transplant recipient with Candida albicans contamination of preservation fluid.

Reported rates of positive preservation fluid cultures range from 5% to 23%, with fungi accounting for 2-10% of all positive cultures. We report the case of a kidney transplant recipient who received a graft with preservation fluid contaminated by Candida albicans, who developed acute renal failure due to ureteral obstruction by fungus balls. The patient was treated with voriconazole with complete restoration of graft function. This rare clinical entity demonstrates the usefulness of pre-transplant cultures of preservation fluid, in order to identify a group of patients who could benefit from antifungal prophylaxis therapy and thereby prevent the need for graft nephrectomy.

Kidney transplantation: future challenges.

Kidney transplantation is the best replacement therapy for the patients with end-stage renal disease, by offering an increased longevity and quality of life. However, the demand for kidney exceeds the available supply, so that the number of people on waiting list is steadily increasing. Many transplant centers have tried to supply to this chronic shortage of organs, by utilizing kidney from older donors or from donors with a previous hepatitis, and this strategy resulted in a safe way to increase the donor pool. Living transplantation has progressively increased in last years so that the number of living donors exceeds in the USA the deceased donors. Although one-year graft survival is excellent, long-term outcomes has not improved in last years. Death from cardiovascular disease, infection and malignancy are common complications of immunosuppression and are the leading causes of mortality in kidney transplant recipients. Viral infections and donor-transmitted infections will be probably the emerging challenge in the next years. Physicians must be aware in developing newer immunosuppressive regimens, with lower side effects, which may improve the long-term outcome of kidney transplantation. Reduction of death with functioning graft and chronic allograft nephropathy will be the greatest challenge of all physicians who care for kidney transplant recipients.

Return to Work and Quality of Life: A Psychosocial Survey After Kidney Transplant.

BACKGROUND: The main goals of kidney transplantation are to recreate a condition of psychophysical well-being and to improve the quality of life of the patient, including going back to work after transplant. Returning to work after a kidney transplant is an important health care indicator. The aim of the study was to assess the psychophysical well-being and work condition in kidney transplant recipients and to identify possible predictors of return to work. PATIENTS AND METHODS: A total of 81 patients (mean age, 46.3; SD, 11.47) were selected among patients undergoing 1 or more kidney transplants during follow-up 12 months after transplant. Pre- and post-transplant employment were evaluated using a sociodemographic schedule. Short Form Health Survey 36 was used for the quality of life study. RESULTS: Only 38.3% of patients were back to work 12 months after transplant compared with 67.90% of pretransplant patients (P = .004). The unemployment rate increased from 32.1% to 61.7% (P = .005) after kidney transplant. The reasons for not returning to work included the type of work (eg, factory) and the disability pension. The sociodemographic characteristics of the study population was significantly correlated with the dimensions of the Short Form Health Survey 36. CONCLUSIONS: Kidney transplant recipients should be encouraged to go back to work until it is a risk to physical health. In this regard, there is a need for multidisciplinary collaboration with the psychologist and the psychiatrist on the team, which provides psychological support and cures any psychological fragility in the post-transplant condition.

Psychological and Emotional Aspects in Living Donor Kidney Transplantation.

BACKGROUND: The decision to resort to living donor transplantation determines a particular condition characterized by a strong mental and emotional anguish, both for the patients and their families. The purpose of the study was to correlate the relational dynamics between donor-recipient, donor/recipient couple with the health team, and the family support perceived by the couple with the quality of life 6 months before transplant and 12 months after transplant and compare the data between the 2 time points after participating in the psychotherapy program of counseling about behavioral change. PATIENTS AND METHODS: Twenty-seven donor and recipient pairs consented to participate. The quality of life was studied through the Complete Form Health Survey (SF-36). All subjects completed a questionnaire that investigated the 3 types of fundamental relationships (donor-recipient, donor/recipient with the health team, and family support perceived by the couple). All participants were involved in an 18-month psychotherapy program in the pre- and post-transplant phase. RESULTS: The quality of the donor-recipient relationship significantly positively influences the subjective perception of psychophysical well-being before and after transplant. Post-transplant family support is crucial in ensuring a good perception of psychological and emotional health in donors and recipients. The relationship with the health team is important in ensuring a good perception of psychophysical health only in recipients after transplant. CONCLUSIONS: This study suggests that patients should be assisted by a multidisciplinary health care team and receive continuous support from relatives during the post-transplant adaptation process. This facilitates the donor and recipient postoperative quality of life.

Infective complications in renal allograft recipients: epidemiology and outcome.

INTRODUCTION: Successful renal transplantation strictly depends on good control of rejection and better prevention and treatment of infections, which remain serious threats. METHODS: This retrospective, observational study of 245 renal allograft recipients who underwent transplantation between January 2002 and December 2005 included a 21+/-10 months follow-up. RESULTS: A total of 110 (44.9%) patients developed an infective process during the posttransplantation period, namely, 232 infective processes. Eighty patients developed at least 1 episode of urinary tract infection (UTI) 11 patients (4%) had a wound infection, and 30 patients (12%) had pneumonia. We diagnosed 35 cases of bacteremia (35%), whereas cytomegalovirus (CMV) infection was demonstrated in 40 patients (16%). CONCLUSIONS: Immunosuppressive therapy, necessary to avoid acute and chronic rejection, exposes patients to a higher rate of infectious complications. The immunosuppressive protocols led to a relatively low incidence of infectious complications, mainly of little clinical significance. The highest incidence was evident by the sixth month after transplantation, when the immunosuppressive regimen exercised its most depressive effects on patient immune systems.

New-onset diabetes mellitus after kidney transplantation: the role of immunosuppression.

BACKGROUND: Complications related to posttransplantation immunosuppressive therapy remain common. New-onset diabetes mellitus after transplantation (PTDM) is a well-recognized complication associated with reduced graft and patient survival. The type of immunosuppression may be responsible for more than two thirds of PTDM. We retrospectively reviewed our experience in a population of 284 kidney transplant recipients, evaluating the incidence of PTDM with regard to the type of immunosuppression. PATIENTS AND METHODS: From January 2001 to December 2005, 284 kidney transplantations were performed using tacrolimus-based (TAC) immunosuppression in 192 patients and a cyclosporine-based (CyA) regimen in 62 patients, whereas 30 patients received sirolimus-based immunosuppression. RESULTS: The overall incidence of PTDM was 4.9%. Among the immunosuppression protocols, 8 patients (4.1%) received TAC and 6 patients (9.6%) received CyA, whereas no patients treated with sirolimus developed PTDM. Graft and patient survival rates were 93% and 100%, respectively. CONCLUSIONS: The overall risk of PTDM with recent immunosuppressive protocols is low, but it is increased among calcineurin inhibitor (CNI)-treated kidney transplant recipients. Sirolimus did not increase the risk of PTDM, allowing potential clinical application in diabetic recipients and in patients affected by PTDM.

Clinical impact of culture-positive preservation fluid on solid organ transplantation: A systematic review and meta-analysis.

Contamination of the preservation fluid (PF) used for donated organs is a potential source of post-transplant infection. However, the information on this issue is scarce. We therefore conducted a systematic review and meta-analysis to assess the incidence of culture-positive PF and its impact on solid organ transplant (SOT) recipients. Seventeen studies were identified and included. The overall incidence of culture-positive PF was 37% (95% CI: 27% to 49%), and the incidence of PF-related infections among SOT recipients with PF cultures that grew pathogenic microorganisms was 10% (95% CI: 7% to 15%). There were differences in the rates of infections due to pathogenic microorganisms between SOT recipients who received pre-emptive treatment and those who did not, but without statistical significance. The mortality rate among SOT recipients with PF-related infection was 35% (95% CI: 21% to 53%). In conclusion, although contamination of the PF of donated organs is frequent, the incidence of PF-related infection is relatively low. A closely clinical and microbiologic monitoring of the SOT recipient in case of culture-positive PF, regardless of the type of microorganism isolated might be do in order to establish a prompt diagnosis of PF-related infection.

Depression and quality of life in living related renal transplantation.

BACKGROUND: More than other operations on the body, organ transplantation has a psychological resonance relating to the self and body image representation, both in donors and in recipients. In the medical literature there are many psychopathological patterns related to ESRD and to the changes in psychologic assessment and lifestyle after transplantation. Similar changes have been found in living donors. METHODS: Forty-eight donor-recipient couples were evaluated before and 4 months after transplantation, using clinical interview, according to the DSM IV TR criteria; The structured Interview for renal transplantation, both for recipients and for donors; psychodiagnostic tests: mini-mental state; Hamilton Rating Scale for Depression; Hamilton Anxiety Scale; Self-Rating Anxiety Scale; Short-Form 36 Health Survey Questionnaire. RESULTS: Comparisons by paired Students t tests showed a significant Hamilton depression variation among recipients, with improvement in the gained score and reduction of depressive symptom (Hamilton score >7) frequency from 45.8% to 32%, and a decreased proportion of patients with a score >18 from 16.4% to 0%. There was no significant Hamilton Depression variation among donors, but there was somehow a reduction in depressive symptom frequency (Hamilton score >7) from 37.5% to 33.3% and a decrease among >18 scores from 12.6% to 0% patients. CONCLUSIONS: Living donor kidney transplantation did not adversely affect the lives of donors and significantly improved many aspects of the lives of recipients. However, physical and psychological aspects may be impaired by living donation. Careful donor selection, with appropriate pretransplantation psychiatric consulting, allows those with a normal life quality to donate without consequence to their physical or psychological status.

Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemia-reperfusion injury.

Nitric oxide (NO), produced by nitric oxide synthase, is implicated in the pathophysiology of renal ischemia/reperfusion (I/R) injury. This study sought to elucidate the impact of pharmacological induction of heme oxygenase-1 (HO-1) on renal I/R injury. Rats were subjected to 45 minutes of renal ischemia followed by various times of reperfusion (30 minutes, 1 hour, or 3 hours). Plasma from sacrificed rats was obtained, and the kidneys processed for the expression of iNOS, cleaved caspase-3, p38MAPK and for immunohistochemical analysis. Furthermore, we determined renal and plasma levels of lipid hydroperoxides, total thiol groups, and plasmatic NO2-/NO3- formation. Our results showed a time-dependent increase in iNOS expression, which was also confirmed by increased plasma formation of NO2-/NO3-. Interestingly, this effect was reversed by pretreatment (12 hours) with SnCl2, a potent and specific inducer of renal HO-1 expression and activity, or by intraperitoneal injection of biliverdin (10 mg/kg). Furthermore, we observed a concomitant reduction in plasma and renal LOOH formation, a normalization of renal total thiol content, a reduction of caspase-3-mediated apoptosis, and a significant increase in p38MAPK phosphoration. Taken together, these results suggested that HO-1 and its byproduct biliverdin play major roles in the pathophysiological cascade leading to renal I/R injury.

Fenoldopam vs dopamine as a nephroprotective strategy during living donor kidney transplantation: preliminary data.

UNLABELLED: Fenoldopam is a selective DA1 agonist with potential nephroprotective capabilities. The aim of this study was to compare the nephroprotective effect of fenoldopam and dopamine during general anesthesia for living donor kidney transplantation. METHODS: Forty donors enrolled in the study received a similar anesthetic and fluid protocol. The patients were randomly divided into group F (receiving 0.1 mg*kg-1*min-1 fenoldopam) versus group D (receiving "renal dose" 3 mg*kg-1*min-1 dopamine). The mean volume of infused fluids, diuresis, and urinary electrolytes (Na, K, Cl) at infusion start and 120 minutes later were studied. RESULTS: Anthropometric parameters, administered anesthetics, mean infused volume, and urine outputs, did not show significant differences between the groups. Statistically significant differences were observed for urinary excretion of sodium, potassium, and chloride after 120 minutes of continuous fenoldopam infusion, with significant variations within groups for sodium only. CONCLUSIONS: Fenoldopam compared with dopamine resulted in better nephroprotective effects. No adverse events were recorded, and side effects were minimal. Further studies are necessary to evaluate these data.

Monolateral dual kidney transplantation from marginal donors.

BACKGROUND: Dual kidney transplantation (DKT) offers a safe way to face the organ shortage with good short-term and medium-term renal function. However, its application is limited by the longer operating time and the risk of surgical complication. This study reviews our results with DKT performed with an ipsilateral technique in terms of graft loss, graft and patient survival rates, and surgical complications. PATIENTS AND METHODS: From January 2002 to March 2006, 23 patients underwent DKT through a monolateral Gibson incision with placement of both kidneys. RESULTS: One primary nonfunction occurred (4%). Delayed graft function was observed in 3 DKT (13.3%). Acute rejection rate was 4.3% (1 patient). All patients are alive at a mean follow-up of 28 months. One-year and 2-year graft survival rates were 100% and 96%, respectively. Mean serum creatinine level at 1-year posttransplantation was 1.3 mg/dL (range, 0.8-2.1 mg/dL). One DKG recipient lost 1 graft, retaining the second normal functioning graft due to ureteral necrosis. The mean hospital stay after transplantation was 15 days (range, 12-34 days). CONCLUSIONS: Monolateral placement in DKT offers the advantage of a single incision, minimizing the surgical risk. Tailored immunosuppression and careful selection of potential recipients, by excluding those with severe cardiopulmonary pathologies, could significantly improve both patient and graft survival in this group of patients.

Voriconazole in the treatment of invasive aspergillosis in kidney transplant recipients.

BACKGROUND: Aspergillosis and other invasive mold infections are severe complications in immunosuppressed patients, and in renal transplant patients it is the most common cause of systemic fungal disease with an incidence ranging from 0.4% to 2.4% with a high mortality of 56% to 100%. We present our experience with voriconazole in a population of kidney transplant recipients with invasive aspergillosis. PATIENTS AND METHODS: From January 2002 to December 2005, 245 kidney transplantations were performed. RESULTS: Four patients (1.6%) presented with clinical and laboratory findings of invasive aspergillosis. Three patients presented with pulmonary aspergillosis, while one patient presented with pulmonary and ocular aspergillosis. All patients underwent a therapy with voriconazole 200 mg twice a day, in combination with caspofungin in one patient. All patients are alive, with no clinical recurrence of aspergillosis at a median follow-up of 13 months. One patient lost her graft due to discontinuation of immunosuppression. CONCLUSIONS: Voriconazole is a potent and well-tolerated antifungal drug that is extremely efficacious in the treatment of invasive aspergillosis in kidney transplant recipients. A careful monitoring of immunosuppressive drugs should be considered to avoid nephrotoxicity.

Alexithymia in Kidney Transplantation Patients.

Alexithymia is a marked difficulty in recognizing, exploring, and expressing inner feelings. Studies have proven the presence of a significant proportion of patients with alexithymia in samples from the transplantation population. This study aims to analyze the presence of alexithymia in a sample of 32 kidney transplantation patients from a deceased donor and to compare this construct with the presence of psychological symptoms and the physical and mental state of health perceived by the patients. Alexithymia assessment was analyzed using the Toronto Alexithymia Scale. The psychological symptoms were studied through the Symptom Checklist-90-R. The quality of life was studied through The Complete Form Health Survey. The study showed a high percentage of the presence of alexithymia in the examined transplant recipients. The construct is more present where the perception of their quality of life is low and where there is a greater presence of psychosomatic symptoms.

Redefining the Pulvinar Sign in Fabry Disease.

BACKGROUND AND PURPOSE: The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity. MATERIALS AND METHODS: We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls. RESULTS: The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables. CONCLUSIONS: The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease.

Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group.

Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months-4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment. We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.