Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients.

BACKGROUND: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a de-centralized approach has been implemented in 2009. AIMS: The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. MATERIALS AND METHODS: Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. RESULTS: In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. CONCLUSION: The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients.

Transperineal ultrasonography in perianal Crohn's disease and recurrent cryptogenic fistula-in-ano.

AIM: Successful anal fistula care is aided by specialized imaging accurately defining the site of the internal opening and fistula type. Imaging techniques are complementary, designed to answer specific anatomical questions. There are limited data concerning the clinical value of transperineal ultrasound (TP-US) in both cryptogenic fistula-in-ano and perianal Crohn's disease (PACD). The aim of the study was to assess the accuracy of TP-US compared with operative findings in patients with perirectal sepsis. METHOD: Patients with recurrent cryptogenic anal fistula and PACD referred for sonography were examined using TP-US by a single examiner blinded to the operative results. Fistulae were categorized by the Parks classification predicting the site of the internal fistula opening. Ancillary horseshoe collections, abscesses and secondary tracks were defined. RESULTS: Fourteen patients with PACD and 27 patients with recurrent cryptogenic fistula-in-ano were analysed with comparative images and operative data. Correlation of fistula type for cryptogenic and PACD patients respectively was 23/27 (85.2%) and 12/14 (85.7%), with a correlative internal opening site (when found at surgery) of 16/22 (72.3%) and 12/14 (85.7%). Misclassification of fistula type in cryptogenic cases occurred in the presence of ancillary abscesses with associated acoustic shadowing. In PACD patients, TP-US was used when anal stenosis precluded endoanal ultrasonography, assisting in the diagnosis of recto-vaginal fistulae. CONCLUSION: TP-US is a useful complementary technique to assess fistula-in-ano and has special advantage when there is anal canal distortion, complex fistula type or suspicion of a recto-vaginal fistula.

Ultrasound in the investigation of posterior compartment vaginal prolapse and obstructed defecation.

Recent developments in diagnostic imaging have made gynecologists, colorectal surgeons and gastroenterologists realize as never before that they share a common interest in anorectal and pelvic floor dysfunction. While we often may be using different words to describe the same phenomenon (e.g. anismus/vaginismus) or attributing different meanings to the same words (e.g. rectocele), we look after patients with problems that transcend the borders of our respective specialties. Like no other diagnostic modality, imaging helps us understand each other and provides new insights into conditions we all need to learn to investigate better in order to improve clinical management. In this review we attempt to show what modern ultrasound imaging can contribute to the diagnostic work-up of patients with posterior vaginal wall prolapse, obstructed defecation and rectal intussusception/prolapse. In summary, it is evident that translabial/perineal ultrasound can serve as a first-line diagnostic tool in women with such complaints, replacing defecation proctography and MR proctography in a large proportion of female patients. This is advantageous for the women themselves because ultrasound is much better tolerated, as well as for healthcare systems since sonographic imaging is much less expensive. However, there is a substantial need for education, which currently remains unmet.

Kidney transplantation--a 46-year experience from the Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.

The limiting factor in organ transplantation is the availability of organs. Ongoing work to improve donation rates both at the public and the organizational level in donating hospitals is essential. We also think that encouragement of live donation is important, and the possibility of ABO incompatible transplantation has increased the number of LD transplantations. The one-year graft survival rate is excellent and focus has shifted towards achieving long-term results to reduce the attrition rate. There is also an increasing interest in studying and working to reduce comorbidities on a long-term basis and thus, improve survival rates and recipient quality of life.

Ultrasonographic assessment of patients referred with chronic anal pain to a tertiary referral centre.

BACKGROUND: Chronic anal pain is relatively common as a presentation to specialist physicians and surgeons. Currently, it is regarded as a functional disorder upon the exclusion of occult intersphincteric sepsis. Our study assessed an unselected cohort of patients presenting with chronic previously undiagnosed anal pain using routine ultrasonography. METHODS: All patients referred to a tertiary gastroenterology service between January 2005 and January 2008 with a diagnosis of chronic anal pain (>3 months duration with no clinical anorectal signs) underwent endoanal and static and dynamic transperineal ultrasound to assess for the frequency and pattern of occult intersphincteric sepsis. RESULTS: Of 1,580 patients referred, there were 146 presenting with chronic anal pain as a main symptom. Of these, 37 (25.3%) had intersphincteric sepsis (ISS) diagnosed with ultrasound examination with 17 undergoing evaluable surgery. There was a male preponderance (70.3%) with the diagnosis being made in 46% of cases after 6 months of symptoms and with 80.8% having posteriorly located sepsis. This occurred on a background of 62% having previous acute proctological conditions. There was complete ultrasonographic and operative concordance with 15 becoming asymptomatic after surgery at a mean follow-up of 6 months. CONCLUSION: Occult intersphincteric sepsis is not uncommon and is diagnosed using routine ultrasonography at the time of clinical presentation. Endoanal and transperineal ultrasound is recommended as part of the investigative armamentarium to exclude categorization as functional anorectal pain. This is currently not part of the Rome III coding for such a diagnosis suggesting a revision of these diagnostic criteria for the ultimate diagnosis of functional proctalgia.

Effect of Flavobacterium columnare inoculation, antibiotic treatments and resident bacteria on rainbow trout Oncorhynchus mykiss eyed egg survival and external membrane structure.

This study was conducted to evaluate the potential pathogenicity of the bacterium Flavobacterium columnare on rainbow trout Oncorhynchus mykiss eyed eggs. Survival to hatching was unaffected by the inclusion in the incubation water of either 300 colony-forming units (CFU) ml(-1) or 3000 CFU ml(-1) of F. columnare at either 10 or 12 degrees C in either McConaughy or Shasta strain eyed eggs. Bacterial numbers, obtained via scanning electron microscopy or culture, and external membrane morphology were also not significantly different among eggs receiving different concentrations of F. columnare. Initial F. columnare burdens were significantly and positively correlated to the presence of biofilm on the egg external membrane, and biofilm was in turn significantly correlated with increased membrane degradation. The use of either streptomycin or tetracyclin antibiotics significantly reduced bacterial numbers on McConaughy strain eggs, and more eggs survived to hatch in those dishes treated with antibiotics.

A comparison of dynamic transperineal ultrasound (DTP-US) with dynamic evacuation proctography (DEP) in the diagnosis of cul de sac hernia (enterocele) in patients with evacuatory dysfunction.

BACKGROUND/AIMS: Cul-de-sac hernias (enterocele and peritoneocele) are difficult to diagnose in patients presenting with primary evacuatory difficulty. Failure to recognize their presence in patients undergoing surgery may lead to poor functional outcome. Accurate diagnosis requires specialized investigation including dynamic evacuation proctography (DEP) or dynamic magnetic resonance (MR) imaging. Recently, dynamic transperineal ultrasonography (DTP-US) has been used for this purpose. This study compares DEP with DTP-US for the diagnosis of cul-de-sac hernias in those patients presenting with evacuatory dysfunction. MATERIALS AND METHODS: Sixty-two female patients with chronically obstructed defecation underwent blinded clinical, DEP, and DTP-US assessment to define the accuracy of diagnosis of cul-de-sac hernias. RESULTS: Both the DEP and the DTP-US techniques show concordance for the diagnosis of cul-de-sac hernias in an unselected patient cohort. Patients in both groups have the same duration of constipation with a greater likelihood of prior hysterectomy in those with cul-de-sac hernias. The diagnosis was established separately by DEP in 88% and in 82% of the cases by DTP-US. Transperineal sonography is discordant with DEP in 45% of cases once the diagnosis of cul-de-sac hernia is made, over the contents of the hernia and over the degree of transvaginal enterocele descent, where DTP-US tends to upgrade enterocele severity. Both techniques confirm the high incidence of concomitant pelvic floor compartment pathology. CONCLUSIONS: Both methods have accuracy for the diagnosis of cul-de-sac hernias in those patients presenting with evacuatory difficulty. Transperineal sonography tends to more readily diagnose peritoneocele and to upgrade enterocele extent. As an office procedure, it is a valuable adjunct to the clinical examination in the diagnosis of cul-de-sac hernia.

Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial.

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.

Infectious complications after multivisceral transplantation in adults.

UNLABELLED: It is thought that multivisceral transplantation requires high levels of immunosuppression and therefore, patients run an increased risk of infection. We retrospectively reviewed our center's experience with clinically relevant infectious complications. PATIENTS: Between 2000 and 2005, 10 adult patients underwent multivisceral transplantation. Two immunosuppression protocols were used: between 2000 and 2003, a high immunosupression protocol (six patients; daclizumab induction, tacrolimus trough levels >20 ng/mL and steroids) and an immunomodulatory, low imunosuppression scheme from 2003 onward (four patients; ATG induction, tacrolimus levels 5 to 10 ng/mL, no steroids). Standard antimicrobial prophylaxis consisted of vancomycin, meropenem, and amphotericin B. Cytomegalovirus (CMV) prophylaxis was used in all but first two cases. Donor and recipient CMV status were D+/R+ (n = 7), D+/R- (n = 2), D-/R+ (n = 1). RESULTS: The median follow-up period was 627 days (range, 19 to 2207 days). A total of 47 infectious episodes were recorded in all patients (range 1 to 14 per patient). The etiology was bacterial in 32 (69%), viral in 8 (17%), and fungal in 7 (14%) cases. The most frequent were catheter related (n = 13) followed by respiratory (n = 7), intraabdominal (n = 6), and wound infections (n = 5). Symptomatic viral infection of the graft (CMV gastritis or enteritis, adenoviral enteritis) was also encountered. Epstein-Barr virus was transiently detected in the serum of nine patients, one of whom later developed posttransplant lymphoproliferative disorder (PTLD). Three deaths all among patients receiving high immunosuppression were owing to infectious complications: pulmonary PTLD at 4 months posttransplantation, ruptured mycotic aneurysm after 8 weeks, and sepsis after 3 weeks. CONCLUSIONS: Infections accounted for a high morbidity after multivisceral transplantation, representing the leading cause of mortality. Exhaustive monitoring, early antimicrobial intervention, and lower immunosuppression may improve the outcome.

Laser-Doppler flowmetry in the monitoring of the human intestinal allograft: a preliminary report.

During acute rejection, graft endothelium becomes a prime target for recipient immune cells. Animal studies have shown reduced microvascular perfusion, probably due to increased endothelial-leukocyte interaction and endothelial impairment, leading to graft damage. Using laser-Doppler flowmetry (LDF), we correlated the microvascular blood flow in the intestinal mucosa of five patients receiving multivisceral grafts with clinical events and pathology results. Measurements (n = 75) were performed during the first 4 weeks posttransplantation by inserting the LDF flexible probe through the ileostomy for 25 to 30 cm. Forty-six of the 75 measurements were performed within 24 hours of endoscopy and biopsy. In uncomplicated cases, we recorded a gradual increase in mucosal perfusion during the first week posttransplantation that presumably reflected regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. Sudden and sustained decreases in mucosal perfusion by 30% or more compared to the previous measurements were associated with septic episodes, rejection, or both. LDF revealed a good sensitivity in monitoring the intestinal microcirculation. It was able to indicate perfusion changes associated with acute rejection. The relatively low specificity of LDF may be compensated by the low invasivity, allowing frequent investigation. LDF may be an additional tool for routine monitoring of intestinal allografts.

Dynamic transperineal ultrasound vs. defecography in patients with evacuatory difficulty: a pilot study.

BACKGROUND AND AIMS: Defecating proctography has been traditionally used to assess patients with evacuatory dysfunction. More recently, dynamic transperineal ultrasound has been described, defining the interaction between the infralevator viscera and the pelvic floor at rest and during straining. This study compared qualitative diagnosis and quantitative measurement obtained by defecography and dynamic transperineal ultrasonography in patients with evacuatory difficulty. PATIENTS AND METHODS: Thirty-three women were examined using both techniques with both examiners blinded to the results of the other method. Quantitative measurement was made of rectocele depth, anorectal angle (at rest and during maximal straining) and anorectal junction position at rest and movement during straining. RESULTS: There was good agreement for the diagnoses of rectocele, rectoanal intususseption, and rectal prolapse. Dynamic transperineal ultrasound was more likely than defecography to make multiple diagnoses or to diagnose an enterocele when a rectocele was present. There was no difference noted between the two techniques for the measurement of anorectal angle at rest, anorectal junction position at rest, or anorectal junction movement during straining. The mean anorectal angle during straining was 123.3+/-4.3 degrees as measured by defecography and 116.4+/-3.3 degrees as measured by dynamic transperineal ultrasound, nearly reaching statistical significance. CONCLUSION: Dynamic transperineal ultrasound is a simple and accurate technique for assessment of the pelvic floor and soft-tissues in patients with evacuatory dysfunction.

Conventional cutting vs. internal anal sphincter-preserving seton for high trans-sphincteric fistula: a prospective randomized manometric and clinical trial.

BACKGROUND: Cutting setons have been used in complicated perirectal sepsis with good effect, although there is a moderately high incidence of fecal leakage after their use. The aim of this study was to compare a modified cutting seton, which repaired the internal anal sphincter muscle and re-routed the seton through the intersphincteric space, with a conventional cutting seton. METHODS: A total of 34 patients were randomized between 1998 and 2002. They were prospectively assessed by continence score and anorectal manometry, and for anal function, clinical sepsis and fistula recurrence. RESULTS: There was no difference in postoperative continence score, incidence of recurrent fistula or healing time between groups after a mean follow-up of 12 months. Resting anal manometric pressures and vector volumes were consistently higher with the modified seton (although not statistically significant), as was the area under the inhibitory curve during elicitation of the rectoanal inhibitory reflex across the full sphincter length. ( p<0.05). CONCLUSION: A larger prospective study of internal anal sphincter-preserving seton use in cryptogenic high transshincteric fistula-in-ano appears justified.

Rectocele: pathogenesis and surgical management.

BACKGROUND: Rectocele is a common finding in patients with intractable evacuatory disorders. Although much rectocele surgery is conducted by gynecologists en passant with other forms of vaginal surgery, many reports lack appreciation of the importance of coincident anorectal symptoms, and do not report functional and clinical outcome data. The pathogenesis of rectocele is still controversial, as is the embryological and anatomical importance of the rectovaginal septum as well as recognizable defects in its integrity and its relevance in formal repair when rectocele is operated upon as the principal condition in patients with intractable evacuatory difficulty. DISCUSSION: The investigation and surgical management of rectocele is controversial given the relatively small numbers of operated patients in any single specialist unit and the relative lack of prospective data concerning functional outcome in operated cases. The imaging of rectocele patients is currently in a state of change, and the newer diagnostic modalities including dynamic magnetic resonance imaging frequently display a multiplicity of pelvic floor disorders. When surgery is indicated, coloproctologists most commonly utilize an endorectal defect-specific repair, but there are few controlled randomized data regarding outcome and response criteria of specific symptoms with particular surgical approaches. A Medline-based literature search was conducted for this review to assess the clinical results of defect-specific rectocele repairs using the endorectal, transvaginal, transperineal, or combined approaches. Only the studies are included that report both pre- and postoperative symptoms including constipation, evacuatory difficulty, pelvic pain, the impression of a pelvic mass, fecal incontinence, dyspareunia or the need for assisted digitation to aid defecation. CONCLUSION: The history of rectocele repair, its clinical and diagnostic features and the advantages, disadvantages and indications for the different surgical techniques are presented in this review. Suggested diagnostic and surgical therapeutic algorithms for management have been included. It is recommended that a multicenter controlled randomized trial comparing surgical approaches for symptomatic evacuatory dysfunction where rectocele is the principal abnormality should be conducted.

Influence of nutrition level on digestibility in high yielding cows and effects on energy evaluation systems.

The objective of the study was to determine the effect of nutrition level (NL, multiples of maintenance energy requirement) on the digestibility of nutrients for dairy cows regarding the energy supply of the animal. The digestion of nutrients and energy was investigated in two trials using lactating dairy cows. The NL varied from 2.7 to 5.0 using diets similar composition. In addition, sheep were given the same feed with a NL of 1.4. Digestibility of dry matter (DM) and all specific measures of dietary components declined significantly as NL increased. Digestibility of energy decreased by 4.1% for each increase in NL. The metabolizable energy, the ability to metabolize energy (metabolizable energy/gross energy), and the content of net energy for lactation (NE(L)) per kilogram of DM intake were calculated for NL from 1 to 6 on the basis of these relationships and as well as the gross energy, methane energy, and urine energy. Accordingly the NEL content declined by 0.11 MJ/kg of DM intake or 1.6% as the NL increased by one unit. It means that the NE(L) requirement above the maintenance requirement increased by 0.07 MJ of NE(L) per kilogram of fat-corrected milk, if the NL increased by one unit.

The pathology and molecular biology of anal intraepithelial neoplasia: comparisons with cervical and vulvar intraepithelial carcinoma.

BACKGROUND: Anal intraepithelial neoplasia (AIN) is a well-described pathological precursor of invasive squamous cell carcinoma which has recently been detected with increasing frequency in immunocompromised patients, particularly those with seropositivity for human immunodeficiency virus (HIV). The epidemiology and natural history of this entity is somewhat unclear, since the overall prevalence in the HIV seronegative population is unknown. DISCUSSION: There is a clear etiological association between AIN and high-risk human papillomavirus (HPV) subtype infection although there is great variability in HPV DNA detection of cytological and histological material in these patients. It appears that there is an antigen-specific hyporesponsiveness by cytotoxic lymphocytes against HPV peptide sequences or recombinant proteins encoded by oncogenic HPV subtypes in these patients, which is dependent upon the stage of their HIV-associated disease. Although the molecular biology of AIN and cervical or vulvar intraepithelial neoplasia are comparable, in AIN there is less significance of tumor suppressor gene mutations, proto-oncogenic growth factor activation, and genomic instability. CONCLUSION: Current concepts in the epidemiology and etiology of AIN are discussed, as well as its immunological response in the HIV-positive population, drawing parallels where possible between other HPV-related preinvasive disorders, and concluding with a suggested management protocol

The management of presacral masses in the adult.

Presacral (retrorectal) tumors are particularly rare in the adult. There is difficulty in the performance of diagnostic biopsy, and specialized imaging is required to plan surgical extirpation. This review assesses their incidence and classification as well as the principles involved in their diagnosis and surgical management.

Rectoanal inhibition and rectocele: physiology versus categorization.

Some authors divide rectoceles into those with chronic evacuatory difficulty and normal genital position (type 1) and those with associated pelvic organ prolapse (type 2). This study assessed whether there are physiological differences between these two clinical rectocele types. Female patients were assessed by conventional anorectal manometry, vector manometry, parametric assessment of the rectoanal inhibitory reflex (RAIR), and defecography. Subjects included 33 volunteer controls without anorectal disease, 14 patients with type I rectocele, and 26 patients with type II rectocele. Significant differences were noted for resting pressure measurements (maximal resting anal pressure and vector volume) between rectocele types and between type I patients and controls. Significant differences were noted for squeeze parameters (maximal squeeze pressure and vector volume) only between rectocele types. There were minimal differences in parameters of the RAIR, with a reduced slope of inhibition in the proximal sphincter for both rectocele groups and a reduced maximal inhibitory pressure in the intermediate and distal sphincter of type 1 rectocele patients. There were no differences in transient excitation of the pressure wave during the RAIR reflex to account for pressure variations with no measured differences in rectocele depth (type 1, 2.87 +/- 0.7 cm; type 2, 2.84 +/- 1.4 cm) There are few physiological differences between the different clinical categories of rectocele patients based on the presence or absence of associated genital prolapse.

Fecal incontinence after minor anorectal surgery.

PURPOSE: Fecal leakage after open lateral internal anal sphincterotomy for chronic anal fissure is common, but underreported. The aim of this study was to prospectively assess the physiologic and morphologic effects of sphincterotomy, comparing continent and incontinent patients after surgery. This group was further compared with an unselected group of patients presenting with incontinence after hemorrhoidectomy. METHODS: Between January 1997 and June 1999, 23 patients were prospectively followed up through internal sphincterotomy with conventional and vector volume anorectal manometry, parametric assessment of the rectoanal inhibitory reflex, and endoanal magnetic resonance imaging. Fourteen continent patients were compared with 9 incontinent postoperative cases, 9 patients referred with incontinence after hemorrhoidectomy, and 33 healthy volunteers without anorectal disease. RESULTS: Significant differences were noted between continent and incontinent postsphincterotomy cases for all resting conventional and vector volume parameters and for some squeeze parameters. Although there was a significant reduction in postoperative high pressure zone length at rest, there were no differences between the postoperative groups. There was an increase in sphincter asymmetry of 6.7 percent (+/- 3.5 percent) in incontinent postsphincterotomy patients and a decrease of 2.8 percent (+/- 3.2 percent) in continent cases. Significant differences were noted for resting parameters between incontinent postsphincterotomy and posthemorrhoidectomy patients, with a higher resting sphincter asymmetry in the latter group. The area under the rectoanal inhibitory curve was smaller in postsphincterotomy incontinent patients when compared with continent cohorts over the distal and intermediate sphincter zones at rest with a reduced latency of inhibition. There was no difference in the magnetic resonance images of the sphincterotomy site between incontinent and continent postsphincterotomy cases and no posthemorrhoidectomy case had evidence of sphincteric damage. CONCLUSION: There are complex significant differences in the postoperative physiology of patients undergoing lateral internal sphincterotomy who become incontinent when compared with those who maintain continence. These physiologic changes are not reflected in detectable morphologic sphincteric differences. It is unknown whether these changes predict for long-term incontinence, and it is suggested that postoperative incontinence after minor anorectal surgery is not necessarily related either to a preexisting sphincter defect or inadvertent intraoperative sphincter injury.