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Transglutaminase 2 (TG2) is an enzyme with multiple conformations. In its open conformation, TG2 exhibits transamidase activity linked to fibrosis, arterial remodeling, and endothelial dysfunction, a process enhanced by high glucose in endothelial cells. However, the closed conformation of TG2 contributes to transmembrane signaling and nitric oxide (NO)-dependent vasorelaxation. LDN 27219, a reversible allosteric inhibitor, stabilizes TG2 in its closed conformation.  We examined whether pharmacological modulation of TG2 into its closed conformation induces vasorelaxation and enhances endothelium-dependent and independent relaxation in resistance arteries from age-matched diabetic (n=14) and non-diabetic patients (n=14) (age 71  (SEM: ±2).

Background: Postoperative ileus (POI), characterized by absent gastrointestinal motility, is a frequent complication following major abdominal surgery, with no current effective treatment possibilities. For further research in the treatment of this condition, we aimed to establish a porcine model of POI., Methods: A total of 12 Landrace pigs, weighing 60 kg, were included. Five animals were used as pilots to establish the surgical procedure, five animals received the same reproducible surgical procedure developed in the pilot experiments, while two animals were used as control. The primary endpoint was number of days to first stool. Intestinal motility was monitored using the SmartPill system., Key Results: Four of the five pigs who underwent the final surgical procedure passed first stool on the third postoperative day (POD), and one passed first stool on the fifth POD. SmartPill data showed retention of the capsule in the stomach in four of five pigs with usable traces., Conclusion and Inferences: An experimental porcine model of POI was established, forming the basis for future studies in POI., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres., Background Data: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement., Methods: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres., Results: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%., Conclusions: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres., Competing Interests: Conflicts of interest and disclosures: Julio Garcia-Aguilar disclosures - Ethicon (Professional Services and Activities) and Intuitive Surgical Inc. Equity (Professional Services and Activities)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3-12.1) vs. 12.5 months (95% CI: 11.2-13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2-46.8) vs. 40.8 months (95% CI: 28.8-46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS.

Background: Chemoradiotherapy is the primary treatment for anal cancer. 15-33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery. Relapse after surgery, postoperative complications, and mortality as well as possible risk factors are not fully understood due to the rareness of the disease. The aim of the study was to report outcomes after salvage surgery as well as evaluate risk factors for postoperative complications, cancer relapse and survival., Methods: Data were retrospectively collected from electronical patients charts and pathology reports from all patients undergoing salvage surgery from July 1st , 2011 to July 1st , 2021 at the Department of Surgery, Aarhus University Hospital, Denmark., Results: A total of 98 patients were included in the study. The 5-year overall survival was 61.8%. Relapse after surgery occurred in 36.7% of patients and was significantly associated with R1-resection (HR = 4.4) and preoperative nodal metastases (HR = 4.5). Negative prognostic factors for survival were found to be R1-resection (HR = 3.2), preoperative nodal metastases (HR = 2.9), and male gender (HR = 0.5). There was no association found between complications and survival (HR 1.2). None of the possible risk factors were associated with major postoperative complications., Conclusions: An acceptable overall survival after surgery was found. Survival and relapse-free survival was negatively associated with R1 resections and positive preoperative lymph nodes. Complications did not influence long-term survival., (© 2023 Published by Elsevier Ltd.)

Objectives: Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2 % of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice., Methods: This was a retrospective national cohort study. All patients were treated at Aarhus University Hospital; the only CRS+HIPEC centre in Denmark. We included CRC patients managed with curative intent for simultaneously diagnosed PM and LM in the period January 2016 - December 2021. LM was treated with RFA as first choice, if possible. Survival was calculated by the Kaplan-Meier method., Results: A total of 25 patients were included, the median age was 60 years (range 43-75 years) and 15 (60 %) were females. The median peritoneal cancer index was 7 (range 0-12), the median number of LM was 1 (range 1-3). Ablation was performed as the only treatment for LM in 18 (72 %) patients. After a median follow-up time of 17.1 months (range 4-36 months), the median OS was 28.6 months (95 % confidence interval (Cl) 15.8;36.1), 1-year OS was 84.0 % (95 % Cl 62.8;93.7). Median DFS was 6.1 months (95 % Cl 4.0;10.3). Median LOS was ten days (range 5-26 days). Both 30-day and 90-day mortality were 0 %., Conclusions: The selected treatment modality (RFA) for CRC patients with both LM and PM was safe. However, DFS was low. Further research is warranted to investigate if RFA is as effective as LM resection., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Pelvic exenteration is a procedure with high morbidity despite careful patient selection. This study investigates potential associations between perioperative markers and major postoperative complications including survival., Methods: Retrospectively collected data for 195 consecutive patients who underwent total pelvic exenteration (January 2015-February 2020) at a single tertiary university hospital were analyzed., Results: The 30-day mortality was 0.5%, and the rate of major postoperative complications (≥3 Clavien-Dindo) was 34.5%. Low albumin level (p = 0.02) and blood transfusion (p = 0.02) were significantly correlated with a major postoperative complication in univariate analyses. This had no impact on survival. Positive margins (p = 0.003), liver metastasis (p = 0.001) were related to poor survival in multivariate analyses for colorectal patients. A Charlson Comorbidity Index >6 (p < 0.05) was associated with poor survival in all patients., Conclusion: The occurrence of major postoperative complication does not negatively impact the overall survival. Pelvic exenteration is a potential life-prolonging operation when negative margins can be obtained, despite known risks for complications. Comorbidity is a predictor for inferior outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Intraabdominal and retroperitoneal sarcomas (IaRS) are malignant connective tissue tumors. Surgical resection is often the only curative treatment. The primary objective was to report the mid-term outcomes following contemporary treatment protocols and identify prognostic factors., Methods: A retrospective review of consecutive patients (n = 107) with IaRS treated at single center from 2013 until 2018 was conducted. Histological diagnosis, tumor grade, perioperative complications, mortality, and long-time survival were registered and retrieved from patient records. Primary and recurrent tumors were analyzed separately., Results: A total of 107 patients were identified. Median follow-up time was 3.5 years. Thirty-day mortality was 3.4% and 90-day mortality was 5.6% for all tumors. The major complication rate was 18%. The 5-year estimated survival for primary and recurrent tumors was 55.4% and 48.4%, respectively. Multifocal disease was evident in 32% of the patient cohort, and 58% of patients in the recurrent group. Multivariate analysis for survival revealed a hazard ratio (HR) of 3.1 (95% CI 1.68-8.41) for multifocality, HR 2.9 (95% CI 1.28-6.98) for Clavien-Dindo grade, HR 2.3 (95% CI 1.21-4.31) for tumor grades 2 or 3, and HR 1.002 (95% CI 1.001-1.004) for surgical margins., Conclusions: Our study found overall acceptable morbidity and mortality, and identified prognostic markers for overall survival. Recurrent tumors were not associated with worse survival. Multifocality is associated with a worse overall survival. The prognostic factors identified were; tumor grade, multifocality, intralesional margins and postoperative complications., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aims to evaluate how metastases in the seven topographical regions of the simplified peritoneal cancer index (sPCI) affect the survival of patients treated with cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) from colorectal (CRC) or appendiceal cancers., Methods: Data was collected retrospectively from patient records. Abdominal regions affected by PC were identified using the histological verification of surgically removed tumours found in the electronic pathology report. Verified tumours were grouped according to the sPCI topography., Results: One hundred and eighty-three patients treated with CRS and HIPEC were included. Metastases in the small bowel had a negative impact on survival with a hazard ratio of 1.89 (p=0.005). A significantly impaired survival was also detected for patients affected by metastases in the ileocolic region (p=0.01) and in the omentum and spleen (p=0.04)., Conclusions: When selecting patients for CRS and HIPEC a more cautious approach may be applied by considering the regions affected., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Lise Hommelgaard et al., published by De Gruyter, Berlin/Boston.)

Introduction: Peritoneal metastases (PM) originating from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP) can be treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Certain sites in the peritoneal cavity are prone to contain PM and are, therefore, routinely resected. The aim of this study is to investigate the frequency of disease in CRS specimens routinely resected. Secondly, to investigate if the risk of finding PM in routinely resected specimen is associated with involvement of anatomic related peritoneal areas., Materials and Methods: This study investigated 433 patients diagnosed with PMP (n = 119) or PM from CRC (n = 314) and operated with CRS + HIPEC between June 2006 and November 2020 at a national center. Baseline data were prospectively registered. Pathology reports were reviewed for the presence of metastases in the routinely resected umbilicus, ligamentum teres hepatis, ovaries and greater omentum. Tumor extent was estimated using the Dutch region count., Results: PM was found in 14.7% of umbilical resections, in 17.4% of the resected ligamentum teres hepatis, in 48.2% of the resected ovaries and in 49.5% of the greater omentum specimens. We found an association between macroscopic disease involvement of the nearest region and risk of PM found in the related resections. Seven of 31 women with no macroscopically visible disease in the pelvis had PM diagnosed in the resected ovaries., Conclusions: A substantial proportion of routine resections held histologic verified PM. Our results may advocate for a routinely performed resection of the umbilicus, ligamentum teres hepatis, ovaries and greater omentum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has become the mainstream treatment for peritoneal metastases of colorectal origin. This extensive treatment is known for its increased morbidity rate. In this study, the impact of postoperative complications on survival was evaluated in a high-volume centre., Patients and Method: Between November 2016 through October 2018, all 106 patients with peritoneal metastases of colorectal origin treated with CRS + HIPEC with oxaliplatin were evaluated. Data on patient characteristics, Peritoneal Carcinomatosis Index (PCI), operative procedure, post-operative complications (Clavien-Dindo classification grade III or higher) and survival were collected. In-hospital postoperative complications were analysed for their association with patient characteristics, tumour load (PCI), and operative procedure with logistic regression analyses. Survival was analysed with the Cox regression analysis., Results: Of 106 patients, 78% had an un-eventful in-hospital recovery. Of those patients who experienced complications, 52% patients had one complication and 48% had more than one. The median follow-up time was 33.8 months. Median survival was 22.4 months (95% CI 12.2-NR) for patients who experienced complications and not reached for those who did not. Survival was significantly associated with complications (HR 2.2, 95% CI 1.2-4.0) as well as with PCI (HR 1.1, 95% CI 1.1-1.2) in univariate analyses. A stepwise Cox regression analysis showed both PCI and complications had an independent negative impact on survival., Conclusion: Postoperative complications, independently of tumour load, led to reduced survival in patients with peritoneal metastases of colorectal origin when treated with CRS + HIPEC with oxaliplatin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Patients with peritoneal malignancy treated by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) are prone to develop postoperative paralytic ileus (POI). POI is associated with significant increase in both morbidity and mortality. CRS and HIPEC commonly result in prolonged POI (PPOI). The objective was to clarify the extent of PPOI in patients treated by CRS and HIPEC for peritoneal malignancy., Methods: This was a prospective multicenter study including patients operated with CRS and HIPEC at the Department of Surgery, Aarhus University Hospital, Denmark and the Peritoneal Malignancy Institute, Basingstoke, United Kingdom. A total of 85 patients were included over 5 months. Patients prospectively reported parameters of postoperative gastrointestinal function in a diary from post-operative day 1 (POD1) until discharge. PPOI was defined as first defecation on POD6 or later., Results: Median time to first flatus passage was 4 days (range 1-12). Median time to first defecation was 6 days (1-14). Median time to removal of nasojejunal tube was 4 days (3-13) and 7 days (1-43) for nasogastric tube. Forty-six patients (54%) developed PPOI. Patients with PPOI had longer time to first flatus (p<0.0001) and longer time to removal of nasojejunal tube (p=0.001). Duration of surgery correlated to time to first flatus (p=0.015) and time to removal of nasogastric or nasojejunal tube (p<0.0001) but not to time to first defecation (p=0.321)., Conclusions: Postoperative gastrointestinal paralysis remains a common and serious problem in patients treated with CRS and HIPEC., Competing Interests: Competing interests: The author(s) have no affiliations or financial involvement with any organization or entity with a financial interest or financial conflict with the study subject or materials discussed in the manuscript., (© 2020 Nors et al., published by De Gruyter.)

Post-operative ileus (POI) is a common complication following especially open abdominal surgery. This review is an overview of the incidence, the current treatment and the future perspectives for POI. Adherence to the enhanced recovery programmes is of great importance, as it has shown a decreased length of POI and length of stay. No single treatment modality has proven effective as a cure for POI.

Introduction: Inflammatory Breast Cancer (IBC) is a distinct and rare type of breast cancer accounting for up to 6% of all breast cancer cases in Europe. The aim of this study was to investigate diagnostic methods, treatments, and outcome after IBC in patients treated at a single institution in Denmark., Method: All patients treated for IBC at Aarhus University Hospital between 2000 and 2014 were identified and included in the cohort. Survival was assessed using Kaplan-Meier curves and log-rank statistics., Results: A total of 89 patients were identified with a median follow up of 3.6 years. The overall survival at 5 and 10 years were 41% and 18%, respectively. The disease free survival at 5 and 10 years were 47% and 27%, respectively. Thirty-four percent had distant metastasis at time of diagnosis. Patients with ER positive tumors had a significantly better overall survival than patients with ER negative tumors (p = 0.01)., Conclusion: Despite a more aggressive systemic and loco-regional treatment today, IBC is still a very serious disease with a high mortality.

Background: Postoperative ileus and anastomotic leakage severely impair recovery after colorectal resection. We investigated the effect of perioperative lipid-enriched enteral nutrition versus standard care on the risk of postoperative ileus, anastomotic leakage, and other clinical outcomes., Methods: We did an international, multicentre, double-blind, randomised, controlled trial of patients (≥18 years) undergoing elective colorectal surgery with primary anastomosis at six clinical centres in the Netherlands and Denmark. Patients were randomly assigned (1:1), stratified by location (colonic and rectal) and type of surgery (laparoscopic and open), via online randomisation software, with block sizes of six, to receive either continuous lipid-enriched enteral tube feeding from 3 h before until 6 h after surgery (intervention) or no perioperative nutrition (control). Surgeons, patients, and researchers were masked to treatment allocation for the entire study period. The primary outcome was postoperative ileus. Secondary outcomes included anastomotic leakage, pneumonia, preoperative gastric volumes, time to functional recovery, length of hospital stay, the need for additional interventions, intensive care unit admission, postoperative inflammatory response, and surgical complications. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175979, and trialregister.nl, number NTR4670., Findings: Between July 28, 2014, and February 20, 2017, 280 patients were randomly assigned, 15 of whom were excluded after random allocation because they fulfilled one or more exclusion criteria. 265 patients received perioperative nutrition (n=132) or standard care (n=133) and were included in the analyses. A postoperative ileus occurred in 37 (28%) patients in the intervention group versus 29 (22%) in the control group (risk ratio [RR] 1·09, 95% CI 0·95-1·25; p=0·24). Anastomotic leakage occurred in 12 (9%) patients in the intervention group versus 11 (8%) in the control group (RR 1·01, 95% CI 0·94-1·09; p=0·81). Pneumonia occurred in ten (8%) patients in the intervention group versus three (2%) in the control group (RR 1·06, 95% CI 1·00-1·12; p=0·051). All other secondary outcomes were similar between groups (all p>0·05)., Interpretation: Perioperative lipid-enriched enteral nutrition in patients undergoing elective colorectal surgery has no advantage over standard care in terms of postoperative complications., Funding: Netherlands Organisation for Health Research and Development (ZonMW), Fonds NutsOhra, and Danone Research., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In order to improve the surgical treatment of rectal cancer, robot-assisted laparoscopy has been introduced. The robot has gained widespread use; however, the scientific basis for treatment of rectal cancer is still unclear. The aim of this study was to investigate whether robot-assisted laparoscopic rectal resection cause less perioperative pain than standard laparoscopic resection measured by the numerical rating scale (NRS score) as well as morphine consumption., Methods: Fifty-one patients were randomized to either laparoscopic or robot-assisted rectal resection at the Department of Surgery at Aarhus University Hospital in Denmark. The intra-operative analgetic consumption was recorded prospectively and registered in patient records. Likewise all postoperative medicine administration including analgesia was recorded prospectively at the hospital medical charts. All morphine analogues were converted into equivalent oral morphine by a converter. Postoperative pain where measured by numeric rating scale (NRS) every hour at the postoperative care unit and three times a day at the ward., Results: Opioid consumption during operation was significantly lower during robotic-assisted surgery than during laparoscopic surgery (p=0.0001). However, there were no differences in opioid consumption or NRS in the period of recovery. We found no differences in length of surgery between the two groups; however, ten patients from the laparoscopic group underwent conversion to open surgery compared to one from the robotic group (p=0.005). No significant difference between groups with respect to complications where found., Conclusions: In the present study, we found that patients who underwent rectal cancer resection by robotic technique needed less analgetics during surgery than patients operated laparoscopically. We did, however, not find any difference in postoperative pain score or morphine consumption postoperatively between the robotic and laparoscopic group.

Background: Paralytic postoperative ileus (POI) is associated with increased morbidity and mortality after abdominal surgery. Despite increased awareness and implementation of various measures, POI remains a problem, perhaps moreso for those patients undergoing extensive oncological surgical treatment. The aim of this study was to describe the extent of POI after advanced cancer surgery in the era of contemporary treatment modalities of POI., Methods: A retrospective analysis of all patients who underwent either abdominoperineal excision with transpelvic vertical rectus abdominal musculocutaneous (VRAM)-flap after anal cancer or pelvic exenteration at single institution from January 2012 to November 2013 was carried out. Patients were identified from operative codes, and data were retrieved from patient records., Results: Eighty-nine patients were included in the study, 21 abdominoperineal excision and 68 pelvic exenteration procedures. Median nasogastric tube duration was 4 days (range: 0-44). Median time to first flatus was 1 day (range 0-15). Median time to defecation was 3 days (range 0-16 days). Twenty-three patients (28%) experienced prolonged ileus. There was a significant longer time to first defecation for patients who received a VRAM flap (P = 0.046). There was also a significant association between longer operative times and first flatus (P = 0.007)., Conclusions: This retrospective study reveals that POI remains as a significant clinical problem in patients undergoing advanced pelvic cancer surgery, despite the increased awareness and implementation of enhanced recovery protocols. New regimens for better prophylaxis are needed, and further research on POI treatment is important., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Pseudomyxoma peritonei is a rare disease causing peritoneal carcinomatosis. In patients with extensive carcinomatosis, curative treatment is unachievable. Palliative debulking therapy is the only treatment in relieving symptoms. We report our results from palliative debulking surgery at a national pseudomyxoma peritonei center in Denmark., Methods: From January 2007 to October 2012, we performed 27 palliative operations for pseudomyxoma peritonei with debulking at our institution. All patients were evaluated and found eligible for palliative treatment only. Patients were prospectively registered, while perioperative data were collected retrospectively from patient records., Results: The majority of patients (n = 25) received an omentectomy (93%) as the primary procedure. In total, 17 (63%) received additional surgery. Median operative time was 88 min (range: 33-160 min). Median stay at the recovery ward was 6 h (2-288 h). Median hospital stay was 8 days (4-105 days). In all, 23 (85%) patients had no in-hospital complications, whereas 4 patients experienced complications (15%). Two of the complications were mild (Clavien-Dindo grade II), and two experienced severe complications (grade III and IV). Thirty-day mortality was 0%. Median survival was 3.0 years (0.2-6.2 years)., Conclusion: Palliative debulking is a safe procedure with an acceptable morbidity and mortality offering immediate disease control., (© The Finnish Surgical Society 2015.)

Carcinosarcoma of the breast is an extremely rare and highly aggressive breast tumor.It has two distinct malignant cell lines involving epithelial (carcinomatous) and mesenchymal (sarcomatous) components. The literature on the topic is sparse. We report a rare case of carcinosarcoma of the breast containing a small fraction of a pancytokeratin positive sarcomatous-appearing cell population i.e. a metaplastic cell population. The patient was treated with a multidisciplinary approach.

A carcinoma arising in a fibroadenoma is a rare event, which often entails a diagnostic challenge. The most common type is the lobular carcinoma and secondary a ductal carcinoma. We present an extremely rare case of malignant development of an invasive apocrine carcinoma in a complex fibroadenoma and underline the importance for clinicians to recognize the possibility of benign and malignant co-existence especially in older women.

Locally advanced breast cancer (stadium III-IV, T3-4) can involve the thoracic wall as well as larger skin areas. This may result in symptoms such as pain, malodorous wounds, and a reduced quality of life. In some selected cases a palliative surgical intervention may be indicated. This case story present two cases of locally advanced breast cancer which were managed surgically in a co-operation between thoracic, plastic and breast cancer surgeons. Both cases were preoperatively evaluated at a multidisciplinary team conference.

Introduction of stentless valves into clinical practice has not replaced stented valve prosthesis as expected a decade ago. With respect to clinical parameters such as transvalvular pressure differences, left ventricular mass regression as well as a possible survival benefit, there are many contradictory studies published. The overall dilemma is the absence of large randomized studies. This review, therefore, focuses on two issues: Experimental research in order to disclose design advantages or drawbacks and clinical trials expressing the real benefit or risk for the patient. In general, both clinical and experimental studies show that stentless valves have several biomechanical and haemodynamic benefits when compared with stented valves though new generation pericardial valves have excellent blood flow profiles. However, stentless and stented valves seem to perform equally well when it comes to various clinical parameters. In most cases, a stented valve is therefore preferable because of the simpler implantation technique. In order to gain a more widespread clinical use, the design of the stentless valve needs to be improved in order to simplify the implantation.

Background and Aim of the Study: The preservation of aortic root dynamics is considered important for the durability of aortic valve bioprostheses. Stentless heart valves are believed to support physiologic biomechanics. To date, dynamic analysis has been limited to the full root prosthesis, and exclusively in the radial direction. The study aim was to investigate and compare the radial and longitudinal aortic root distensibilities of subcoronary stentless valves, and of stented and native pig valves., Methods: Stented pericardial (Mitroflow) or stentless (Solo, Toronto SPV) valve prostheses, or native porcine valves, were investigated in 32 pigs. Postoperatively, 12 sonomicrometry crystals were placed on the aortic root in order to measure aortic root distensibility, in both radial and longitudinal directions., Results: Sonomicrometry data were obtained from 23 pigs (72%). At the annular level, the native and Solo valves were significantly more distensible in a radial direction than the Mitroflow valve (p = 0.04). However, at the level of the sinotubular junction (STJ), commissures and aorta, the native valve was significantly more distensible than all of the artificial valves (p = 0.006, p = 0.006, and p = 0.02, respectively). The Solo valve exhibited less longitudinal distensibility than the Toronto SPV and Mitroflow valves. The Toronto SPV initiated a radial expansion at the STJ significantly later in the cardiac cycle than did both the Solo and native valves (p = 0.03), but showed no difference compared to the Mitroflow valve. Longitudinal expansion between the annulus and the STJ started significantly earlier for the Solo valve than for both the Toronto SPV (p = 0.03) and Mitroflow (p = 0.02) valves., Conclusion: The Solo valve proved to be superior in maintaining annular distensibility immediately following implantation when compared to the Mitroflow valve. The Solo valve did not, however, preserve longitudinal distensibility as well as the other investigated valves. Finally, the Solo valve appeared to provide a more physiologic aortic root expansion pattern than its prosthetic counterparts.

Regions of turbulence downstream of bioprosthetic heart valves may cause damage to blood components, vessel wall as well as to aortic valve leaflets. Stentless aortic heart valves are known to posses several hemodynamic benefits such as larger effective orifice areas, lower aortic transvalvular pressure difference and faster left ventricular mass regression compared with their stented counterpart. Whether this is reflected by diminished turbulence formation, remains to be shown. We implanted either stented pericardial valve prostheses (Mitroflow), stentless valve prostheses (Solo or Toronto SPV) in pigs or they preserved their native valves. Following surgery, blood velocity was measured in the cross sectional area downstream of the valves using 10MHz ultrasonic probes connected to a dedicated pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at two different blood pressures (baseline and 50% increase). We found no difference in maximum RNS measurements between any of the investigated valve groups. The native valve had significantly lower mean RNS values than the Mitroflow (p=0.004), Toronto SPV (p=0.008) and Solo valve (p=0.02). There were no statistically significant differences between the artificial valve groups (p=0.3). The mean RNS was significantly larger when increasing blood pressure (p=0.0006). We, thus, found no advantages for the stentless aortic valves compared with stented prosthesis in terms of lower maximum or mean RNS values. Native valves have a significantly lower mean RNS value than all investigated bioprostheses., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Glutaraldehyde-treated bioprosthetic heart valves are commonly used for replacement of diseased heart valves. However, calcification and wear limit their durability, and the development of new and improved bioprosthetic valve designs is needed and must be evaluated in a reliable animal model. We studied glutaraldehyde-treated valves 6 months after implantation to evaluate bioprosthetic valve complications in the mitral position in juvenile pigs., Materials: The study material comprised eight, 5-month old, 60-kg pigs. All pigs received a size 27, glutaraldehyde-treated, stented, Carpentier-Edwards S.A.V. mitral valve prosthesis. After six months, echocardiography was performed, and the valves explanted for gross examination, high resolution X-ray, and histological evaluation., Results: Five pigs survived the follow-up period. Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively. Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves. High resolution X-ray imaging revealed different degrees of calcification in all explanted valves, primarily in the commissural and belly areas. In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium., Conclusions: Bioprosthetic glutaraldehyde-treated mitral valves can be implanted into the mitral position in pigs and function after 6 months. Echocardiographic data, calcification, and histological examinations were comparable to results obtained in sheep models and human demonstrating the suitability of the porcine model.

Background and Aim of the Study: Glutaraldehyde-preserved bioprosthetic heart valves are non-viable and have a limited durability because of calcification, tissue wear, and inflammation, especially in children. Decellularized porcine heart valves, when treated with deoxycholic acid (DOA), have exhibited complete recellularization and an absence of calcification when implanted into the pulmonary position in juvenile sheep. The study aim was to determine the degree of recellularization and calcification in DOA-treated heart valve prostheses in the mitral position in juvenile pigs., Methods: A mitral heart valve prosthesis was implanted into each of 17 pigs, and subsequently explanted and fixed in formaldehyde after between five and 26 weeks. A gross pathologic assessment, high-resolution X-ray imaging and histological examination were then performed on each valve., Results: Eight pigs survived the observational period. Five valves had only a slight fibrin deposition and calcification foci within the fibrin deposits. Three valves had severe thrombotic material deposits with disseminated calcification and valve stenosis, and one valve had infective endocarditis. A myofibroblast-like cell ingrowth was observed at different locations of the valve housing in all explanted heart valves, but ingrowth in the basal part of the cusp matrix was limited. In four valve prostheses, endothelial cells covered up to 10% of the cusp surface after six months. Inflammatory cells were observed in large numbers in those valves showing endocarditis and severe thrombosis, but in only limited numbers in the other valves., Conclusion: All valves showed the deposition of fibrin and platelet material, in three cases to a severe degree. A limited ingrowth of both endothelial and myofibroblast-like cells was observed in five valves in which calcification was limited to a few commissural foci. The non-endothelialized surface of the decellularized valves makes them very susceptible to platelet and fibrin deposition; however, slow revitalization seems possible.

A flexible aortic root is essential for natural leaflet stress distribution. It is suggested that stentless bioprosthetic valves retain the flexibility of native valves. We investigated aortic root distensibility and cross-sectional area (CSA) in stentless (Solo, n=4; Toronto SPV, n=7), stented (Mitroflow, n=8) and in native valves (n=8) in pigs. Magnetic resonance imaging was performed to assess aortic root areas. At the annular level the Solo valve had a larger CSA (2.83+/-0.26 cm(2)) than both the Mitroflow (2.24+/-0.23 cm(2)) and Toronto SPV (1.87+/-0.59 cm(2)) (P=0.003; P=0.01). At the sino-tubular junction the Mitroflow valve had a significantly larger CSA (2.96+/-0.80 cm(2)) than the Toronto SPV (2.05+/-0.47 cm(2); P=0.02). At the annular level the percentage change in area between end-diastole and end-systole was lower for the Mitroflow than for all the other valves (P=0.006). No difference was found between native and stentless valves. In conclusion, the Solo valve had a larger CSA at the annulus than both the Mitroflow and the Toronto SPV. However, the stentless valves had a smaller CSA at the sino-tubular junction than the Mitroflow. We, furthermore, found that implantation of stentless heart valves preserves aortic root distensibility at the annular level in pigs.

Background and Aim of the Study: Abnormal flow conditions across aortic bioprosthetic valves may result in degenerative processes. Thus, it is important to implant biological valve prostheses with velocity profiles similar to those of native valves. The study aim was to compare blood velocity and velocity gradient profiles downstream of stented and stentless aortic valves implanted in pigs, and in native porcine valves., Methods: Stented valve prostheses (Mitroflow, n = 7) or stentless valve prostheses (Solo, n = 5 or Toronto SPV, n = 7) were implanted into pigs; the native valve was retained in eight animals. After weaning the animals from cardiopulmonary bypass, cardiac magnetic resonance imaging was performed to determine the blood velocities and velocity gradient profiles., Results: The native valves had a significantly lower peak velocity (92 +/- 26 cm/s) than the artificial valves (Solo: 247 +/- 107 cm/s; Toronto: 252 +/- 41 cm/s; Mitroflow: 229 +/- 18 cm/s). The native valves exhibited a flat velocity profile during systole, whereas the Solo valve, and especially the Toronto SPV valve, displayed more parabola-shaped velocity profiles; velocity profiles downstream of the Mitroflow valve exhibited a flat shape. The native valves had a lower mean velocity gradient at peak systole (p < 0.0001). The velocity gradient percentage above mean was lowest for the native valve (0.14 +/- 0.11; p < 0.0001), while the Mitroflow valve had a percentage of 0.57 +/- 0.09, which was lower than the Solo valve (0.69 +/- 0.12; p = 0.074), and significantly lower than the Toronto valve (0.70 +/- 0.08; p = 0.015). All valves displayed high velocity gradients adjacent to the aortic wall; in particular, the Toronto SPV which also had high velocity gradients at the center of the vessel., Conclusion: All of the artificial valves tested had a significantly higher mean velocity gradient and peak velocity than the native valves. However, the Mitroflow had a mean velocity and a velocity gradient percentage lower than the two stentless valves. The Solo and Mitroflow valves displayed velocity profiles most like native valves, while the Toronto valve had a more irregular asymmetric velocity profile.

Introduction: Surgical ventricular reconstruction is an option for treatment of heart failure elicited by left ventricular aneurism. The aim of this study was to report the results of such treatment in our tertiary centre., Material and Methods: From January 2002 through October 2007 surgical ventricular restoration was performed in 26 patients (23 males) with a median age of 64 years (47-74 years). Twenty-one of the patients were in New York Heart Association (NYHA) class III-IV. The median preoperative left ventricular ejection fraction was 27% (13-38%). We collected both pre- and postoperative data retrospectively., Results: Eighty-five percent of the patients received additional operative procedures, in most cases coronary artery bypass grafting. Ninety-six percent survived the follow-up period which had a median duration of 392 days (1-1777). At follow-up left ventricular ejection fraction had increased to 35% (18-53%) (p < 0.05) and 20 patients were in NYHA class I-II (p < 0.05)., Conclusion: Surgical left ventricular reconstruction is a feasible option for treatment of heart failure in patients with post myocardial infarction aneurisms. In selected patients this treatment carries a low mortality and results in improved left ventricular function and functional capacity.

This case report describes three cases of acute massive pulmonary embolism treated with surgical embolectomy at Skejby Sygehus (Aarhus University Hospital), Denmark, in the period from March 2005 to January 2006. It was necessary to open each pulmonary artery in all three patients in order to remove as much of the embolic material as possible. The three patients survived the operation, although one had hypoxic brain damage resulting from cardiac arrest prior to hospitalization. They all had normal echocardiography postoperatively. Surgical embolectomy is therefore a feasible treatment for acute massive pulmonary embolism.

Objective: Mechanical heart valves can cause thromboembolic complications, possibly due to abnormal flow patterns that produce turbulence downstream of the valve. The objective of this study was to investigate whether three different bileaflet valve designs would exhibit clinically relevant differences in downstream turbulent stresses., Methods: Three bileaflet mechanical heart valves (Medtronic Advantage), CarboMedics Orbis Universal and St. Jude Medical Standard) were implanted into 19 female 90 kg pigs. Blood velocity was measured during open chest conditions in the cross sectional area downstream of the valves with 10 MHz ultrasonic probes connected to a modified Alfred Pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at three different cardiac output ranges (3-4, 4.5-5.5, 6-7 L/min)., Results: Data from 12 animals were obtained. RNS correlated with increasing cardiac outputs. The highest instantaneous RNS observed in these experiments was 47 N/m2, and the mean RNS taken spatially over the cross sectional area of the aorta during systole was between 3 N/m2 and 15 N/m2. In none of the cardiac output ranges RNS values exceeded the lower critical limit for erythrocyte or thrombocyte damage for any of the valve designs., Conclusions: Reynolds normal stress values were below 100 N/m2 for all three valve designs and the difference in design was not reflected in generation of turbulence. Hence, it is unlikely that any of the valve designs causes flow induced damage to platelets or erythrocytes.

Background: Animal experimental testing is imperative for preclinical evaluation of prosthetic heart valves and implantation techniques. Because human and pig cardiovascular structures including mitral valves show remarkable anatomical similarity, these animals are good candidates for preclinical testing. Previous attempts to establish such long-term models were hampered by both intra- and postoperative difficulties. Our aim was to overcome these difficulties to develop a porcine model for mitral valve replacement (MVR) and furthermore to investigate the practical feasibility of 3 chordal reconstruction procedures., Methods: Sixteen 60-kg pigs were allocated to undergo 1 of 3 surgical procedures, (1) preservation of the entire subvalvular apparatus (n = 8), (2) preservation of the secondary chordae only (n = 4), or (3) excision of the native valve and papillary resuspension with sutures (n = 4). St. Jude Medical valves (29 mm) were implanted during extracorporeal circulation and cold cardioplegic arrest. Postoperative anticoagulation was administered by subcutaneous heparin injections., Results: Fourteen animals survived 1 month, thriving and without signs of heart failure. One animal was euthanized due to irreversible bleeding in the tracheal tube, and another animal died on the third postoperative day owing to valve thrombosis., Conclusion: A practically feasible long-term porcine model of MVR has been established. Because the pig is superior to other species with respect to anatomical and physiological similarity to humans, we consider this model as an optimal platform for experimental preclinical testing of heart valve prostheses.