Felix Aigner

The Vascular Nature of Hemorrhoids

The arterial blood supply of the internal hemorrhoidal plexus is commonly believed to be associated with the pathogenesis of hemorrhoids. Ultrasound-supported proctoscopic techniques with Doppler-guided ligature of submucosal rectal arteries have been introduced for the therapy of hemorrhoids. The present investigation focuses on caliber and flow changes of the terminal branches of the superior rectal artery (SRA) supplying the corpus cavernosum recti (CCR) in patients with hemorrhoids. Forty-one outpatients (17 female, 24 male; mean age 48 years) with hemorrhoids of Goligher grades I-IV were compared with 17 healthy volunteers (nine female, eight male; mean age 29 years) by means of transperineal color Doppler ultrasound. The mean caliber of the arterial branches in the study group with hemorrhoids was 1.87±0.68 mm (range, 0.6 to 3.60 mm) and 0.92±0.15 mm (range, 0.6 to 1.2 mm) in the control group (P<0.001). The arterial blood flow was significantly higher in patients with hemorrhoids than in the control group (mean 33.9 vs. 11.9 cm/second, P<0.01). Our findings demonstrate that increased caliber and arterial blood flow of the terminal branches of the SRA are correlated with the appearance of hemorrhoids. We suggest that the hypervascularization of the anorectum contributes to the growth of hemorrhoids rather than being a consequence of hemorrhoids. Transperineal color Doppler ultrasound (CDUS) is an appropriate method to assess these findings in patients with hemorrhoids.

Lipocalin-2 Regulates the Inflammatory Response During Ischemia and Reperfusion of the Transplanted Heart

Ischemia and reperfusion (IR) are known to negatively affect early allograft function following solid organ transplantation. Lipocalin‐2 (Lcn‐2) has been described as a marker and potential positive modulator of acute inflammation during these processes. Using a heterotopic murine heart transplant model we previously found that IR resulted in a pronounced upregulation of Lcn‐2 mRNA in the heart at 12 (22.7‐fold increase) and 24 h (9.8‐fold increase) of reperfusion. We now confirm this increase at the protein level and provide evidence for infiltrating polymorphonuclear cells as the primary source of Lcn‐2 protein. Lcn‐2 levels are increased 6.6‐fold at 12 h, 11.4‐fold at 24 h and 6.4 fold at 48 h after reperfusion. In Lcn‐2−/− grafts the number of infiltrating granulocytes is reduced by 54% (p < 0.05) at 2 h, 79% (p < 0.01) at 12 h, 72% (p < 0.01) at 24 h and 52% (p < 0.01) at 48 h after reperfusion compared to Lcn‐2+/+ grafts, without any differences in cardiomyocyte apoptosis. These data suggest a function of Lcn‐2 in the initiation of the inflammatory response. Moreover, an increase in Lcn‐2 is not only restricted to the transplanted heart, but is also observed in the kidney, hinting at a possible involvement of Lcn‐2 in the systemic response to IR.

Local administration of cidofovir for human papilloma virus associated skin lesions in transplant recipients

Human papilloma virus (HPV)‐associated diseases are increasingly diagnosed in solid organ recipients. Cidofovir (CDV) is a broad‐spectrum antiviral agent with activity against all human herpes viruses and HPV. From 2000–2004, a total of 1303 solid organ transplants (SOT) were performed at our center. Six transplant recipients were treated with topical CDV for HPV‐associated lesions. One cardiac recipient responded to a single injection of CDV into his recurrent anal condylomata. In a renal recipient with recurrent penile condylomata CDV was injected into the lesions four times (2 week interval) until lesions regressed. One renal recipient developed multiple vaginal and anal intradermal neoplasias, which relapsed after laser ablation. The lesions were repeatedly injected with CDV and completely disappeared. Two renal recipients with widespread verrucae vulgares were treated with CDV gel, which resulted in regression of the lesions. One patient developed donor derived verrucae vulgares on both transplanted hands, which responded to CDV gel. Four of the six patients were switched from calcineurin inhibitors (CNIs) to Sirolimus (SIR). CDV was found effective in the treatment of HPV‐associated skin lesions in SOT recipients. It needs to be determined whether switch from CNIs to SIR might have contributed to the beneficial effect of CDV.

Stapled transanal rectal mucosectomy ten years after.

Stapled mucosectomy (SM) was first proposed for the management of patients with rectal internal mucosal prolapse and obstructed defecation, but gained popularity worldwide for the treatment of hemorrhoids. The present review highlights the advantages and disadvantages of the operation. SM tends to decrease postoperative pain and shortens convalescence after hemorrhoid surgery, but may be followed by severe complications, e.g. rectal obliteration and pelvic sepsis requiring a diverting stoma, more frequently than after standard hemorrhoidectomy. Moreover it carries a higher recurrence rate in the treatment of fourth-degree piles. A recent Cochrane metaanalysis demonstrated that SM is less effective than standard hemorrhoidectomy since it carries a higher recurrence rate (OR=3.6) and reintervention rate (OR=2.3). When used for rectal mucosal prolapse and obstructed defecation, SM is reported to have variable results. A better outcome is likely to be achieved in patients without anismus and psychoneurosis operated on by specialists trained with this technique.

Epithelial and Muscular Regionalization of the Human Developing Anorectum

In the past, interpretations of anorectal development were mainly based on analysis of serially sectioned embryos of various nonhuman species as well as some human specimens. A four‐dimensional view of the developmental situation in the human has never been established nor connected to recent findings obtained from newer molecular techniques. We, therefore, investigated human embryonic and fetal pelves by means of immunohistochemistry and in situ hybridization to elucidate differentiation and interaction of epithelial and mesenchymal layers of the anorectum. To emphasize spatial as well as sequential morphological development, we produced three‐dimensional reconstructions of the specimens at hand. Research conducted proved that the decisive steps of epithelial and muscular differentiation occur between the 7th and 9th week after conception. This study elucidates a biphasic epithelial “closure” in the anal canal and interactions between epithelium, smooth musculature, and skeletal musculature. Based on the results presented here, it is possible to describe the pathogenesis of two anorectal malformations: the imperforate anal membrane and the anal membrane stenosis. This study will now provide the basis for further research into developmental processes occurring before the ones examined. Anat Rec, 1449‐1458, 2007.

Malignancies of the colorectum and anus in solid organ recipients.

Patients undergoing solid organ transplantation (SOT) are at increased risk for developing malignancies due to the long term immunosuppression. Data on malignancies of the large intestine after various types of SOT are rare. A total of 3595 SOTs were performed between 1986 and 2005 at our center and retrospectively analyzed with regard to the incidence and course of malignancies of the colon, rectum, and anus. Standard immunosuppression consisted of calcineurin inhibitors in combination with azathioprine or mycophenolate mofetil and steroids with or without antithymocyte globulin or IL‐2 receptor antagonist induction. A total of 206 patients (5.7%) developed malignancies. Colorectal adenocarcinoma was diagnosed in nine patients (0.25%; mean age at diagnosis 65 years) at a mean of 5.3 years after transplantation. Five patients (55%) died 7.2 years post‐transplant due to cardiovascular disease (n = 4) and tumor progression (n = 1). Four patients developed anal neoplasia (0.11%) 7 years post‐transplant with 100% 1‐year survival. Five patients showed post‐transplant lymphoproliferative disorders (PTLD) with intestinal involvement. The incidence of anal but not of colorectal cancers in our transplant recipients differed from that of immunocompetent individuals of corresponding age (0.11% vs. 0.002% and 0.25% vs. 0.3%). PTLD may involve the colon.

Combined pancreas-kidney transplantation for patients with end-stage nephropathy caused by type-2 diabetes mellitus.

Background Simultaneous pancreas-kidney (SPK) transplantation is widely accepted as an optimal therapeutic option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease, but the indication for patients with type 2 diabetes mellitus (T2DM) is still controversially discussed. Methods Twenty-one T2DM recipients of a first combined pancreas-kidney graft performed at our center during a 9-year period were retrospectively analyzed with regard to demographic characteristics; cardiovascular risk factors; surgical, immunological, and infectious complications; and patient and graft survivals and compared with T1DM recipients (n=195) and 32 T2DM patients who received a kidney transplant alone (KTA) during the same period. Results Patient survival at 1 and 5 years was 96.9% and 91.6% for the T1DM group, 90.5% and 80.1% for the T2DM group, and 87.1% and 54.2% for the T2DM KTA group, respectively (P<0.001). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was calculated to be 92.6% and 80.7% for the T1DM group and 81.0% and 75.9% for the T2DM group, respectively (P=0.19). Kidney allograft survival at 5 years was 83.6% for T1DM, 80.4% for T2DM, and 52.7% for T2DM KTA (P<0.0001). Multivariate analysis adjusting for donor and recipient age, secondary complications of diabetes, body mass index, waiting time, cold ischemic time, delayed graft function, and coronary risk factors showed that differences did not remain statistically significant. Conclusion Favorable results can be achieved with SPK transplantation in type 2 diabetics with a low coronary risk profile. A high cardiac death rate impacts results of KTA and calls for stringent selection.

Ventral Hernia Repair in Bariatric Surgery

Background: Obesity is an important risk factor for perioperative complications including the development of ventral hernias. Methods: This retrospective study comprises patients who underwent abdominal hernia repair simultaneously with or following implantation of a Swedish Adjustable Gastric Band® (SAGB). Results: 9 out of 415 patients (2.2%) who received a SAGB between January 1996 and June 2001 underwent ventral hernia repair. In 6 patients, hernias preexisted from previous abdominal surgery at the time of the bariatric procedure, and another 3 hernias occurred at the median and left upper abdominal trocar position following SAGB placement. Median BMI at time of SAGB implantation was 44 (range 35-52), and at time of hernia repair was 36 (range 25-46). 2 hernias were repaired during SAGB placement, 3 during redo surgery, and 2 during abdominoplasty. In 2 patients, significant weight loss with loss of soft tissue support of the hernia sac led to recurrent episodes of small bowel obstruction necessitating emergency repair. Repair included direct defect closure in 7 patients and sublay polypropylene net implantation in 2 patients. Recoveries have been uneventful without wound infections or recurrence in all patients after a median follow-up of 34 months (range 13-69). Conclusion: In morbidly obese patients, the optimal management and timing of incisional hernia repair should weigh the risk of recurrence and perioperative complications against the risk of hernia-associated complications.

Enteroscopic biopsies in the management of pancreas transplants: a proof of concept study for a novel monitoring tool.

Background. Although percutaneous biopsies are considered to be the gold standard in diagnosing pancreas graft rejection, they are not performed routinely because of their association with severe complications. On the other hand, correct diagnosis of rejection is essential but may be difficult in cases of enteric drainage, particularly in patients with a pancreas transplant alone or a pancreas after kidney transplant. Methods. Pancreas recipients who underwent enteroscopy between May 2005 and September 2009 were included in this retrospective analysis. Biopsies were graded 0 to 4 for interstitial and vascular changes. Results. During the study period a total of 65 simultaneous pancreas-kidney transplants, 13 pancreas after kidney transplants and 4 pancreas transplants alone were performed. Sixty-three patients underwent a single enteroscopy, 10 had two, and 6 had three or more. Indications were protocol graft monitoring (n=73), graft dysfunction (n=17), enteric hemorrhage (n=9), or other (n=3). The duodenal segment was accessed in 76 instances (75%) with abnormal findings in 23. A total of 69 biopsies were obtained and revealed normal mucosa in 49 cases (71%). Histology showed signs of acute rejection in 11 cases. The upper gastrointestinal tract was also assessed, and, in 13 cases, additional pathologies were identified including gastroduodenitis (n=10), gastric/duodenal ulcer (n=2), and hemorrhagic esophagitis (n=1). No procedure-related complication occurred. Conclusions. This series of enteroscopies demonstrates that the duodenal segment of a pancreatic graft is accessible using our implant technique, and thus permitting biopsies to be obtained and endoscopic interventions to be performed.

Vascular considerations for stapled haemorrhoidopexy

Objective  Modern haemorrhoidectomy techniques aim to interrupt arterial blood supply to the hypertrophied piles. The aim of this study was to investigate morphological and physiological alterations in the terminal branches of the superior rectal artery (SRA) in patients with haemorrhoidal disease treated by stapled haemorrhoidopexy (SH) using noninvasive transperineal ultrasound.