Recurrence and Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Synchronous and Metachronous Peritoneal Metastases of Colorectal Origin.

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.

Outcomes after curatively intended treatment of limited peritoneal metastases and thermal ablation for liver metastases from colorectal cancer.

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.

Risk factors and outcome following salvage surgery for squamous cell carcinoma of the anus.

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.

Intraabdominal and retroperitoneal soft-tissue sarcomas - Surgical treatment and outcomes.

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.

Complications and survival after total pelvic exenteration.

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.

Peritoneal metastases found in routinely resected specimens after cytoreductive surgery and heated intraperitoneal chemotherapy.

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.

The impact of postoperative complications following cytoreductive surgery combined with oxaliplatin based heated intraperitoneal chemotherapy.

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.

Postoperative paralytic ileus after cytoreductive surgery combined with heated intraperitoneal chemotherapy.

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.

[Post-operative ileus].

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.

Inflammatory breast cancer: A review from our experience.

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.

Perioperative pain after robot-assisted versus laparoscopic rectal resection.

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.

Postoperative paralytic ileus remains a problem following surgery for advanced pelvic cancers.

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.

Breast carcinosarcoma: clinical and pathological features.

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.

Apocrine carcinoma arising in a complex fibroadenoma: a case report.

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.

[Palliative surgery of breast cancer]. / Palliativ kirurgi ved brystkræft.

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.

Current status on stentless aortic bioprosthesis: a clinical and experimental perspective.

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.

Turbulence downstream of subcoronary stentless and stented aortic valves.

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.

Aortic root distensibility and cross-sectional areas in stented and subcoronary stentless bioprostheses in pigs.

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.

[Surgical left ventricle reconstruction for treatment of heart failure]. / Endoventrikulaer venstre ventrikel-rekonstruktion til behandling af hjerteinsufficiens.

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.