Rectal perforation after aquablation of the prostate: lessons learned the hard way.

INTRODUCTION: Transurethral resection of the prostate and open prostatectomy have been the standard of care for the surgical treatment of benign prostatic obstruction (BPO) over decades. New emerging techniques for the surgical management of BPO have been currently introduced, but might be associated with new, unusual complications. METHODS: We herewith report on two patients with a rectal perforation after aquablation treatment of BPO. RESULTS: In the first case, the diagnosis was made 2 days after the aquablation procedure due to unspecific postoperative symptoms. A complex combined open/endoscopic repair of the defect was carried out thereafter. As a consequence, a rectoscopy was routinely performed since then following each aquablation procedure. In the second case, intraoperative rectoscopy after uneventful aquablation revealed the rectal perforation. The perforation was clipped immediately with an over the scope-clip by colonoscopy. CONCLUSIONS: These two cases of a rectal perforation after aquablation of the prostate demonstrate an unusual complication and its complex management. Diagnostic delay complicates its treatment. Therefore, immediate rectoscopy should be performed routinely after the aquablation procedure.

[Malignant epithelioid angiomyolipoma of the kidney: a rare case]. / Malignes epitheloides Angiomyolipom der Niere: ein seltener Fall.

Epitheloide angiomyolipoma (EAML) is a very rare type of benign mesenchymal angiomyolipoma. In contrast to classical angiomylipoma, lymph node metastases, local recurrence and distant metastases occur in one third of patients with EAML. We report the case of a 49-year-old patient with a large recurrence of EAML of the left kidney. According to the literature, this is the first case of a malignant EAML with local recurrence in Germany.

[Rare case of nonparasitic chyluria]. / Seltener Fall einer nichtparasitären Chylurie.

Chyluria, a symptom that is very rare in the western world, describes the excretion of chyle into the urogenital system. We present the case of a 61-year-old woman with a severe form of nonparasitic chyluria. We were able to detect the fistula due to a newly developed diagnostic combination of Sudan III red with ureterorenoscopy. Prior to this, we had performed a lymphoscintigraphy twice without detecting the lymphorenal fistula, although lymphoscintigraphy is the current diagnostic standard. This is the first case report of severe, nonparasitic chyluria.

Recurrence and mortality after breast-conserving surgery without radiation.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer; studies have demonstrated that adjuvant rt confers a protective effect with respect to recurrence, although no randomized trials have shown a survival benefit. Methods: This retrospective cohort study used Ontario data linked through ices to examine patients treated for breast cancer between 1 April 2007 and 31 March 2014. The primary outcome was death or recurrence. Outcomes were compared between patients who did and did not receive rt. Results: The total cohort size was 26,279. The hazard ratios (hrs) for various outcomes were significantly higher for patients who did not receive rt than for patients who did: recurrence or death combined [hr: 2.49; 95% confidence interval (ci): 2.25 to 2.75], recurrence (hr: 2.33; 95% ci: 1.91 to 2.84), and death (hr: 2.28; 95% ci: 2.03 to 2.56). The hr for death was 1.81 (95% ci: 1.65 to 1.99) for patients having stage ii cancer compared with those having stage i disease. The hr for death was 1.97 (95% ci: 1.74 to 2.22) for patients having high comorbidity compared with those having little comorbidity. Conclusions: Adjuvant rt carries a protective effect with respect to recurrence and survival in patients with early-stage breast cancer. That survival benefit has not been appreciated in previous randomized trials and underscores the importance of rt as a component of breast cancer treatment.

EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Appropriate treatment receipt after breast-conserving surgery.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer, although some women receive ipsilateral mastectomy or adjuvant tamoxifen, both of which can be appropriate alternatives to rt. Objectives of the present study were to determine the proportion of women who are treated appropriately after bcs and to identify factors associated with non-receipt of rt. Methods: This retrospective cohort study used Ontario data linked at the Institute for Clinical and Evaluative Sciences to examine 33,718 patients who received bcs during 2004-2010. Primary outcome was rt receipt. The ipsilateral mastectomy rate and patient, surgeon, and setting variables were measured. Results: Of the study patients, 86.1% received either rt or completion mastectomy; in the cohort less than 70 years of age, 90.8% received rt or completion mastectomy. Among patients less than 70 years of age, 3 risk factors for non-receipt of rt were identified: age less than 46 years, treatment in a non-academic institution, and earlier year of initial bcs. Additionally, in the overall cohort, rt non-receipt was associated with high comorbidity, more than 40 km to the cancer centre, income quintile, and breast care specialization. Conclusions: In Ontario, 90.8% of patients less than 70 years of age are appropriately treated for early breast cancer; approximately 1 in 10 do not receive rt or completion mastectomy. Based on those findings, women less than 46 years of age might be at increased risk of recurrence and death because of incomplete treatment. It also appears that academic centres more effectively treat breast cancer; however, breast cancer care appears to be improving over time in Ontario.

Contrast Enhanced Ultrasound can Replace Computed Tomography Angiography for Surveillance After Endovascular Aortic Aneurysm Repair.

OBJECTIVE/BACKGROUND: Surveillance after endovascular aortic aneurysm repair (EVAR) is mandatory and computed tomography angiography (CTA) is considered the standard imaging modality, although patients are exposed to ionizing radiation and nephrotoxic contrast medium. The primary aim of this study was to determine the diagnostic efficacy of duplex ultrasound (DUS) and contrast enhanced ultrasound (CEUS) using CTA as the gold standard. The secondary aim was to determine the clinical consequences of endoleaks missed by DUS and CEUS, or CTA. METHODS: All patients with EVAR for an aorto-iliac aneurysm between 1 August 2011 and 31 October 2014 were prospectively and consecutively enrolled. CEUS was added to the existing surveillance protocol, which included DUS, plain abdominal X-ray, and CTA at 3 and 12 months after stent implantation. RESULTS: In 278 patients, endoleaks were detected in 68, 69, and 46 cases by CTA, CEUS, and DUS, respectively. The sensitivity and specificity of DUS and CEUS were 46% and 93%, and 85% and 95%, respectively. CEUS and CTA were diagnostically equivalent, as opposed to DUS and CTA (p = .002). Endoleaks detected by CTA led to re-intervention in 11 (4%) patients. These endoleaks were also detected by CEUS; however, three out of 11 patients were missed by DUS and underwent re-intervention: limb extension, re-cuff, and attempt to coil lumbar leaks. Endoleaks missed by CEUS or CTA were type II endoleaks without sac expansion. CONCLUSION: In surveillance programs after EVAR a diagnostic CEUS examination may replace CTA.

Are retrievable vena cava filters placed in trauma patients really retrievable?

PURPOSE: Concerns have arisen regarding the use of retrievable inferior vena cava filters (rIVCFs) in trauma patients due to increasing reports of low retrieval rates. We hypothesized that complete follow-up with a dedicated trauma nurse practitioner would be associated with a higher rate of retrievability. This study was undertaken to determine the rate of retrievability of rIVCFs placed in a Canadian Lead Trauma Centre, and to compare the rate of retrievability in our trauma population to our non-trauma patients. METHODS: We performed a retrospective cohort study of all patients with rIVCF placed between Jan 1 2000 and June 30 2014. Data were collected on demographics, indication for filter placement, retrieval status, and reasons for non-retrieval. Comparison was made between trauma patients and non-trauma patients. RESULTS: A total of 374 rIVCFs were placed (61 in trauma patients and 313 in non-trauma patients) and follow-up was complete for the entire cohort. Filter retrieval was achieved in 86.9 % of trauma patients. Reasons for non-retrieval were technical in two patients, and death before retrieval in six patients. Retrieval was successful in 48.9 % of non-trauma patients. CONCLUSIONS: This study demonstrates that rIVCFs can be successfully retrieved amongst trauma patients. We demonstrated a higher rate of successful retrieval amongst trauma patients than non-trauma patients in our institution. Careful patient follow-up may play a role in successful retrieval of rIVCFs.

Non-operative management of blunt hepatic trauma: Does angioembolization have a major impact?

PURPOSE: A paradigm shift toward non-operative management (NOM) of blunt hepatic trauma has occurred. With advances in percutaneous interventions, even severe liver injuries are being managed non-operatively. However, although overall mortality is decreased with NOM, liver-related morbidity remains high. This study was undertaken to explore the morbidity and mortality of blunt hepatic trauma in the era of angioembolization (AE). METHODS: A retrospective cohort of trauma patients with blunt hepatic injury who were assessed at our centre between 1999 and 2011 were identified. Logistic regression was undertaken to identify factors increasing the likelihood of operative management (OM) and mortality. RESULTS: We identified 396 patients with a mean ISS of 33 (± 14). Sixty-two (18%) patients had severe liver injuries (≥ AAST grade IV). OM occurred in 109 (27%) patients. Logistic regression revealed high ISS (OR 1.07; 95% CI 1.05-1.10), and lower systolic blood pressure on arrival (OR 0.98; 95% CI 0.97-0.99) to be associated with OM. The overall mortality was 17%. Older patients (OR 1.05; 95% CI 1.03-1.07), those with high ISS (OR 1.11; 95% CI 1.08-1.14) and those requiring OM (OR 2.89; 95% CI 1.47-5.69) were more likely to die. Liver-related morbidities occurred in equal frequency in the OM (23%) and AE (29%) groups (p = 0.32). Only 3% of those with NOM experienced morbidity. CONCLUSIONS: The majority of patients with blunt hepatic trauma can be successfully managed non-operatively. Morbidity associated with NOM was low. Patients requiring AE had morbidity similar to OM.

Human CD45RA(-) FoxP3(hi) Memory-Type Regulatory T Cells Show Distinct TCR Repertoires With Conventional T Cells and Play an Important Role in Controlling Early Immune Activation.

Adoptive immunotherapy with regulatory T cells (Treg) is a new option to promote immune tolerance following solid organ transplantation (SOT). However, Treg from elderly patients awaiting transplantation are dominated by the CD45RA(-) CD62L(+) central memory type Treg subset (TregCM), and the yield of well-characterized and stable naïve Treg (TregN) is low. It is, therefore, important to determine whether these TregCM are derived from the thymus and express high stability, suppressive capacity and a broad antigen repertoire like TregN. In this study, we showed that TregCM use a different T cell receptor (TCR) repertoire from conventional T cells (Tconv), using next-generation sequencing of all 24 Vß families, with an average depth of 534 677 sequences. This showed almost no contamination with induced Treg. Furthermore, TregCM showed enhanced suppressive activity on Tconv at early checkpoints of immune activation controlling activation markers expression and cytokine secretion, but comparable inhibition of proliferation. Following in vitro expansion under mTOR inhibition, TregCM expanded equally as well as TregN without losing their function. Despite relatively limited TCR repertoire, TregCM also showed specific alloresponse, although slightly reduced compared to TregN. These results support the therapeutic usefulness of manufacturing Treg products from CD45RA(-) CD62L(+) Treg-enriched starting material to be applied for adoptive Treg therapy.

Demethylation of the TSDR is a marker of squamous cell carcinoma in transplant recipients.

Malignancy is an important cause of death in transplant recipients. Cutaneous squamous cell carcinoma (cSCC) causes significant morbidity and mortality as 30% of transplant recipients will develop cSCC within 10 years of transplantation. Previously we have shown that high numbers of regulatory T cells (Tregs) are associated with the development of cSCC in kidney transplant recipients (KTRs). Demethylation analysis of the Treg-specific demethylated region (TSDR) provides a more accurate association with cSCC risk after transplantation. Age, gender and duration of immunosuppression matched KTRs with (n=32) and without (n=27) cSCC, were re-analyzed for putative clinical and immunological markers of cancer risk. The proportion of FOXP3+ CD4+ cells was higher in the population with a previous SCC. Major T cell subsets remained stable over time; although B cell, CD8 and CD4 subpopulations demonstrated age-related changes. TSDR methylation analysis allowed clarification of Treg numbers, enhancing the association of high Treg levels in KTRs with cSCC compared to the cSCC-free cohort. These data validate and expand on previous findings in long-term KTRs, and show that immune markers remain stable over time. TSDR demethylation analysis provides a more accurate biomarker of cancer posttransplantation.

Endograft limb occlusion in EVAR: iliac tortuosity quantified by three different indices on the basis of preoperative CTA.

OBJECTIVE: To assess the incidence and outcome of graft limb occlusions after endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) in a high volume single centre. To quantify iliac artery tortuosity in patients with AAA and correlate this with limb occlusion. DESIGN: Data were collected consecutively and prospectively, and analyzed retrospectively. MATERIALS: Patients treated with Zenith bifurcated stent grafts from January 2000 to December 2010 at a tertiary referral vascular unit were analyzed. Routine regular office follow-up with computed tomography angiography (CTA) and, subsequently, duplex ultrasound imaging was performed. Patients with limb occlusions were identified. For each index patient, two controls were obtained, one immediately preceding and one following the index patient in the consecutive cohort of EVAR patients. METHODS: Demographics and CTA data on limb graft occlusions were recorded and compared with a defined control group. Three different indices were used to describe the tortuosity of the iliac vessels based on preoperative CTA: pelvic artery index of tortuosity (PAI), common iliac artery index of tortuosity (CAI), and a visual description of vessel tortuosity - the double iliac sign (DIS). Demographic data and indices were correlated for later occurring limb occlusion. RESULTS: 504 patients underwent EVAR and 18 patients experienced graft limb occlusion during a median follow-up of 28 months (range 0-133). Primary graft patency was 97% at 1 year and 96% at 3 years. Logistic regression showed that iliac artery tortuosity (DIS) (p = .001) and body mass index (p = .007) had a significant impact on graft patency. CONCLUSION: A tortuous vessel on the preoperative CTA is associated with an increased risk of limb occlusion after EVAR. Adjunctive stenting of iliac segments deemed at risk is suggested, which is achieved without compromise of the aneurysm repair.

Outcomes after elective aortic aneurysm repair: a nationwide Danish cohort study 2007-2010.

OBJECTIVE: To assess outcomes after treatment for asymptomatic abdominal aortic aneurysm (AAA) in Denmark in a period when both open surgery (OR) and endoluminal repair (EVAR) have been routine procedures. METHODS: We performed a retrospective nationwide cohort study of patients treated for asymptomatic AAA between 2007 and 2010. Data on demographics, procedural data, perioperative complications, length of stay (LOS), 30-day reinterventions and readmissions, late aneurysm and procedure-related complications and mortality were obtained from the Danish Vascular Registry and the Danish National Patient Register. RESULTS: 525 EVAR and 1176 OR for asymptomatic AAA were identified. LOS was shorter after EVAR than OR (4 vs. 7 days, p < .001). During primary hospitalization procedure-related complications (12% vs. 6%) and general complications (21% vs. 8%) were more common after OR than EVAR (p < 0.001). The 30-day reintervention rate was higher for OR than EVAR (18% vs. 6%, p < 0.001), but there was no difference in readmissions within 30 days. During follow-up (mean 29 ± 15 months) aneurysm-related complications after EVAR were outweighed by procedure-related complications after OR. CONCLUSION: Elective AAA repair in Denmark is overall comparable with international results and both perioperative and late outcomes after EVAR of elective AAA are better than the results after OR.

GMP-adapted overexpression of CXCR4 in human mesenchymal stem cells for cardiac repair.

BACKGROUND: Human mesenchymal stem cells (MSC) have been utilized for cardiac regeneration after myocardial damage. Their clinical effects are marginal and only a minority of administered cells could make their way into the myocardium. The chemokine receptor CXCR4 has been identified as crucial for migration and homing of stem cells. In this study we overexpressed CXCR4 on human MSC to improve cell trafficking and tissue repair. METHODS: Human MSC were isolated from the spongiosa of tibia and femur as well as from pelvic bone marrow. MSC were characterized by differentiation assays and FACS analysis. CXCR4 was overexpressed by mRNA-nucleofection. Intracellular signaling was analyzed to demonstrate functionality of CXCR4. The modified Boyden chamber, wounding assays and time lapse microscopy were utilized to investigate MSC migration. RESULTS: MSC did not express relevant amounts of CXCR4 spontaneously. CXCR4 could be overexpressed in 93% of MSC with a cell viability of 62%. Functionality of the overexpressed CXCR4 was demonstrated by a significant cytosolic Ca(2+) increase and activation of different MAP kinases followed by SDF-1α stimulation. In contrast no improvement of cell migration could be observed. There was a strong basal MSC chemokinesis independent from CXCR4 expression. CONCLUSIONS: CXCR4 could be effectively overexpressed in human MSC by mRNA-nucleofection. Despite functionality of CXCR4 MSC were characterized by a strong basal chemokinesis that could not be further enhanced by CXCR4 overexpression. As isolation, culture and nucleofection of pelvic bone marrow-derived MSC basically fulfill the GMP-requirements our approach seems suited for an in vivo application in patients.

[Postoperative complications after recrossectomy of the saphenofemoral junction]. / Postoperative Komplikationen nach inguinaler Re-Krossektomie.

The surgical procedure for recurrences at the saphenofemoral junction represents a great challenge for the surgeon due to the complex anatomic variability, the broad range of causes and the mostly extreme scar tissue. The incidences of postsurgical minor and major complications after recrossectomy in the groin area are determined and the clinical outcomes are analysed in this article. After specific and precise presurgical clinical and sonographical diagnoses having been undertaken a cutaneous incision is performed in the groin with the aid of tumescent local anaesthesia combined with total intravenous anaesthesia. From the proximal site any scar tissue exsisting is meticulously removed, the femoral vein is set free and the still remaining stump of the long saphenous vein or of the neovasculate as well as all left over varicose side branches of the saphenofemoral junction are removed. Within this special surgical procedure the stump of the long saphenous vein or the neovasculate are completely removed and, thereafter, a continuous longitudinal suture of the femoral vein is performed. Uncomplicated minor bleeding complications (haematoma in large extension or disseminated) appear quite frequently, lymphatic minor complications (conservatively treatable lymph oedema, lymphatic fistulae or lymphatic cysts) occur from time to time; major complications such as bleeding complications with the necessity of surgical reintervention occur only in sporadic cases and can be avoided by exact presurgical diagnosis, by meticulous special surgical technique matching the operation site as well as by regular and frequent postsurgical follow-ups. Absolute preconditions to achieve the very best results in the long run are the exact procedures of diagnosis and surgical technique. Performed by experienced phlebosurgeons or vascular surgeons, the recrossectomy of the saphenofemoral junction represents a low-risk surgery for the patient and is a singular and possibly time-consuming challenge for the surgeon.

Outcomes following a limited approach to radiotherapy in rectal cancer.

BACKGROUND: Variation in the use of neoadjuvant and adjuvant radiotherapy for rectal cancer suggests an opportunity to avoid it in all but patients at highest risk of local recurrence. METHODS: Between 1 July 1999 and 1 February 2006, patients with primary rectal cancer were treated by a single surgeon operating at McMaster University, Hamilton, Ontario, Canada. Digital rectal examination and pelvic computed tomography were used to determine whether the mesorectal margin was threatened by tumour and thus whether preoperative radiotherapy would be needed. The study outcome was local tumour recurrence. RESULTS: Forty-six (48 per cent) of 96 patients received preoperative radiation therapy. The median follow-up was 4·2 years. Tumours were fixed or tethered in 31 (67 per cent) of the 46 irradiated patients. In contrast, no tumour was fixed in unirradiated patients and only ten (20 per cent) of the 50 tumours were tethered. The proportion of patients with stage I or II tumours based on final pathology was similar: 61 per cent (28 of 46) and 56 per cent (28 of 50) in irradiated and unirradiated groups respectively (P = 0·287). There were four (9 per cent) and two (4 per cent) local recurrences among irradiated and unirradiated patients respectively (P = 0·422). CONCLUSION: Limiting preoperative radiotherapy in rectal cancer to patients with a threatened circumferential margin does not compromise patient outcome.

Incidence of systemic inflammatory response syndrome after endovascular aortic repair.

AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm during 2007, were retrospectively evaluated for SIRS within the first 5 postoperative days. The only exclusion-criteria were missing data. SIRS was assessed using the criteria defined by the American College of Chest Physicians and Society of Critical Care Medicine Consensus Conference Committee. RESULTS: Sixty-six patients were included, 40 (60%) met the SIRS criteria within the first 5 postoperative days (95% of the 40 patients met the criteria within 3 days). We found no significant differences between the SIRS and the non-SIRS group in baseline characteristics or other data including volume of the contrast media used, type of groin access, adjunctive procedures and duration of surgery. In total, 11 (28%) patients in the SIRS group and 4 (15%) patients in the non-SIRS group underwent re-interventions. Median follow-up period was 26 (range 20-32) months. Thirty-day mortality did not differ in the groups (3% in the SIRS group vs. none in the non-SIRS group). CONCLUSION: The high incidence of SIRS after EVAR is unexpected considering the minimally invasive procedure. Further studies on the cause of this response and measures to attenuate the response seem appropriate.

Celiac trunk coverage in endovascular aneurysm repair.

BACKGROUND AND AIMS: This retrospective study was undertaken to examine the risks associated with obstruction of the coeliac trunk in the process of treating aneurysms with endografting. MATERIAL AND METHODS: 120 patients were treated by endografting for aneurysmal disease. Of these, a subgroup of 9 patients had their celiac trunk covered. If possible, a preoperative angiography was performed to evaluate collateral flow from the superior mesenteric artery. This was considered to predict the risk for ischemia. RESULTS: None of the patients had any severe clinical event of the celiac trunk occlusion or clinical signs of intestinal ischemia. Three patients had transient increase of liver enzymes. CONCLUSIONS: In cases where the distal landing zone of the descending thoracic aorta is to short for endografting, covering of the celiac trunk may be an option if no other surgical alter-native is apparent. Preoperative angiography to visualise the presence of collateral vessels from the superior mesenteric artery is recommended.

High weight differences between donor and recipient affect early kidney graft function--a role for enhanced IL-6 signaling.

The frequency of delayed function of kidney transplants varies greatly and is associated with quality of graft, donor age and the duration of cold ischemia time. Furthermore, body weight differences between donor and recipient can affect primary graft function, but the underlying mechanism is poorly understood. We transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. Twenty-four hours posttransplantation, serum creatinine levels in H-WD recipients were significantly higher compared to L-WD recipients indicating impaired primary graft function. This was accompanied by upregulation of IL-6 transcription and increased tubular destruction in grafts from H-WD recipients. Using DNA microarray analysis, we detected decreased expression of genes associated with kidney function and an upregulation of other genes such as Cyp3a13, FosL and Trib3. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and cause tubular damage, whereas immediate neutralization of IL-6 receptor signaling in H-WD recipients rescued primary graft function with well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function.