Corrigendum to "Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis".

[This corrects the article DOI: 10.1155/2020/1385978.].

Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare variant of soft tissue sarcoma (STS). Materials and Methods. We reviewed SFT patients (pts) treated at our institution between 12/1990 and 09/2017. RESULTS: We identified 94 pts with a median follow-up (mFU) of 4.7 years (range: 0.1-21.53). Primary sites were the chest (33%), abdomen (21.3%), brain (12.8%), and extremities (9.6%); 6.4% of pts presented with synchronous metastasis. Median overall survival (mOS) from the first diagnosis was 56.0 months (m) (0.3-258.3). Doege-Potter syndrome was seen in 2.1% of pts. Primary resection was performed in 86 pts (91.5%). Median progression-free survival was 34.1 m (1.0-157.1), and 43% of pts stayed SFT-free during FU. Local recurrence occurred in 26.7% after a mFU of 35.5 m (1.0-153.8), associated with an OS of 45.1 m (4.7-118.2). Metachronous metastasis occurred in 30.2% after a mFU of 36.0 m (0.1-157.1). OS in metastatic pts was 19.0 m (0.3-149.0). Systemic therapy was given to 26 pts (27.7%) with inoperable/metastatic disease. The most common (57.7%) upfront therapy was doxorubicin, achieving responses in 13.3% of pts with a PFS of 4.8 m (0.4-23.8). In second line, pts were treated with ifosfamide or pazopanib, the latter achieving the highest response rates. Third-line treatment was heterogeneous. CONCLUSION: SFT is an orphan malignancy with a highly variable clinical course and a considerable risk of local failure and metachronous metastasis. Surgery is the only curative option; palliative systemic therapy is used in inoperable/metastatic cases but achieves low response rates. The highest response rates are seen with pazopanib in second/third line.

Anti-tumor activity of the MDM2-TP53 inhibitor BI-907828 in dedifferentiated liposarcoma patient-derived xenograft models harboring MDM2 amplification.

PURPOSE: Dedifferentiated liposarcoma (DDLPS) is a soft tissue malignancy characterized by amplification of the mouse double minute 2 homolog (MDM2) gene. MDM2 is a negative regulator of tumor protein 53 (TP53). We tested the in vivo efficacy of BI-907828, a small molecule inhibitor of the MDM2-TP53 interaction, in two DDLPS patient-derived xenografts (PDX). METHODS: Partially immunodeficient mice were bilaterally engrafted with UZLX-STS3 (n = 24) and UZLX-STS5 (n = 24) human DDLPS tissue harboring MDM2 amplifications. Mice were grouped as follows: (a) vehicle (0.5% hydroxyethylcellullose) 10 ml/kg daily per os (p.o.); (b) doxorubicin 5 mg/kg weekly intraperitoneally (i.p.); (c) BI-907828 2.5 mg/kg daily p.o. and (d) BI-907828 10 mg/kg daily p.o. The treatment lasted for 15 days, all mice treated with BI-907828 were followed for 37 days post-treatment. Efficacy was assessed by tumor volume and histopathological evaluation. RESULTS: The 15-day treatment with 2.5 mg/kg and 10 mg/kg BI-907828 significantly inhibited tumor growth in UZLX-STS5 and -STS3 (p < 0.0001 compared to control for both models). All UZLX-STS5 and -STS3 tumors treated with BI-907828 decreased in size during treatment, and BI-907828-treated UZLX-STS5 tumors even disappeared completely. During the follow-up period, no tumor regrowth was observed in the UZLX-STS5 model and both doses of BI-907828 led to a pathological complete response, whereas a dose-dependent regrowth was seen in the UZLX-STS3 model. CONCLUSION: BI-907828 showed significant anti-tumor activity in DDLPS PDX harboring MDM2 amplifications, providing a strong rationale for early clinical testing of BI-907828 in a DDLPS patient population.

A prospective pilot study to assess neoadjuvant chemotherapy for unresectable peritoneal carcinomatosis from colorectal cancer.

AIM: Twelve to 13% of patients with colorectal cancer (CRC) develop peritoneal carcinomatosis (PC), the majority of whom present with unresectable disease. This study aimed to document the actual response rate to and response characteristics of preoperative modern systemic chemotherapy in this patient group. METHOD: Patients underwent a positron emission tomography (PET)/CT scan, laparoscopy and peritoneal biopsy to document unresectable PC. After four courses of preoperative chemotherapy (capecitabine/oxaliplatin ± bevacizumab), the extent of PC was re-evaluated by PET/CT(or CT), laparoscopy and peritoneal biopsy (if considered safe). RESULTS: Ten patients (seven men, three women) with good performance status of median age 60.3 (45.6-72.8) years were studied. The first laparoscopy documented unresectable PC. One patient was excluded because of systemic metastases on PET/CT. Nine proceeded to follow the trial protocol. Of these, one developed early progressive disease, two had macroscopically stable disease and five had progressive disease at second laparoscopy. One patient developed a small bowel perforation at first laparoscopy and received palliative chemotherapy outside the protocol, after which progressive disease was found at an explorative laparotomy. Thus, 7 (78%) patients with unresectable PC from CRC developed progressive disease under neoadjuvant chemotherapy and 2 (22%) patients remained stable. No clear macroscopic response to chemotherapy could be demonstrated. CONCLUSION: Unresectable PC from CRC does not respond well to systemic chemotherapy.

The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study.

BACKGROUND: Oxaliplatin and Mitomycin C (MMC) are both suitable as intraperitoneal chemotherapy agents in HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer (CRC). METHODS: Patient cohorts from two different HIPEC-centers underwent cytoreductive surgery and HIPEC with Oxaliplatin (39 patients) and MMC (56 patients), respectively. They were compared for toxicity and survival data. The extent of PC was assessed using the Dutch 7-region count. RESULTS: The median 7-region count was 4 [range 0-7] for Oxaliplatin-patients versus 2.5 [range 1-6] for MMC-patients (P = 0.004). Median intra-operative blood loss was 650 ml [0-6,000 ml] in Oxaliplatin-patients versus 1,230 ml [range 0-5,300 ml] in MMC-patients (P < 0.001). Only MMC-patients developed neutropenia/leucopenia (26.8%, P < 0.001). After statistical correction for the extent of PC, the overall postoperative complication rate was significantly higher in MMC-patients (OR = 2.68 (95% CI: 1.04-6.91), P = 0.04), with a comparable intra-abdominal complication (IAC) rate (OR = 0.78 (95% CI: 0.30-2.03), P = 0.61), but a tendency towards more extra-abdominal complications (EAC) in MMC-patients (OR = 2.23 (95% CI: 0.91-5.43), P = 0.079). Median follow-up was significantly shorter for Oxaliplatin-patients (2.8 years) than for MMC-patients (5.1 years). Median RFS was 12.2 months [IQR: 7.2-undefined] in the Oxaliplatin-group and 13.8 months [IQR: 7.0-25.8] in the MMC-group (P = 0.87). Median OS is 37.1 months [IQR: 22.4-52.8] for Oxaliplatin-patients and 26.5 months [IQR: 16.9-64.8] for MMC-patients (P = 0.45). Logistic regression analysis (corrected for extent of PC) shows RFS (HR = 1.24 (95% CI: 0.75-2.05), P = 0.39) and OS (HR = 1.37 (95% CI: 0.74-2.54), P = 0.32) are not significantly different. CONCLUSIONS: No clear benefit in RFS and OS for HIPEC with Oxaliplatin or MMC could be demonstrated in patients with PC from CRC.

Optical sensing for tumor detection in the liver.

BACKGROUND: There is an increasing trend for optical guidance techniques in surgery. Optical imaging using Diffuse Reflectance Spectroscopy (DRS) can distinguish different tissue types through a specific "optical fingerprint". We investigated whether DRS could discriminate metastatic tumor tissue from normal liver tissue and thus if this technique would have potential for further implementation into surgical instruments or radiological intervention tools. METHODS: A miniaturized optical needle was developed able to collect DRS spectra between 500 and 1600 nm. Liver specimen of 24 patients operated for colorectal liver metastases were analyzed with DRS immediately after resection. Multiple measurements were performed and DRS results were compared to the histology analysis of the measurement locations. In addition, normal liver tissue was scored for the presence or absence of steatosis. RESULTS: A total of 780 out of the 828 optical measurements were correctly classified into either normal or tumor tissue. The resulting sensitivity and specificity were both 94%. The results of the analysis for each patient individually showed an accuracy of 100%. The Spearman's rank correlation of DRS-estimated percentages of hepatic steatosis in liver tissue compared to that of the pathologist was 0.86. CONCLUSIONS: DRS demonstrates a high accuracy in discriminating normal liver tissue from colorectal liver metastases. DRS can also predict the degree of hepatic steatosis with high accuracy. The technique, here demonstrated in a needle like probe, may as such be incorporated into surgical tools for optical guided surgery or percutaneous needles for radiological interventions.

HIPEC in T4a colon cancer: a defendable treatment to improve oncologic outcome?

BACKGROUND: Adequate estimation of the potential benefits of 'adjuvant' hyperthermia and intraperitoneal chemotherapy (HIPEC) in T4 patients through assessment of the burden of peritoneal carcinomatosis (PC) in T4 tumors and the risk of PC as the only metastatic site. PATIENTS AND METHODS: Analysis of prospectively collected data on patients who underwent surgery for colon cancer (Jan 2004-Jan 2007). RESULTS: About 379 patients (M/F = 204/175) were included, with a median age of 71.8 years (range 35.4-95.0): 39 stage I, 126 stage II, 89 stage III, 116 stage IV disease (+9 with unknown stage). The median follow-up was 34.8months [range 0.0-79.4]. The 3- and 5-year overall survival rates (OS) were 68.4% (95% confidence interval (CI) 63.9%-72.4%) and 60.3% (95%CI 55.6%-64.7%). Relapse analysis was restricted to stages II-III T3 (N = 154) and T4 tumors (N = 19) with complete relapse data, of which 13.2% developed PC. PC has a detrimental effect on OS [HR 6.3 (95%CI: 3.1-13.0, P < 0.0001)]. 50% of T4a and 20% of T4b developed PC. The 1- and 3-year PC percentage was significantly lower for T3 (4.5% and 9.3%) than T4 tumors (15.6% and 36.7%) (P = 0.008). PC was the only metastatic site in 3/15 T3 [proportion 0.20, 95%CI (0.043-0.481)] and 5/8 T4 tumors with PC [proportion 0.625, 95%CI (0.245-0.915)] (P = 0.071). CONCLUSIONS: T4a colon tumors have a significantly higher risk of developing PC. Twenty-five percent (5/19) of stages II-III T4 tumors develop PC as the only metastatic site. This could define the possible window of opportunity for adjuvant HIPEC to prevent PC.

Review: incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer.

OBJECTIVE AND BACKGROUND: This review describes the extent, frequency and clinical importance of Bevacizumab(BV)-related serious adverse events (SAE) after surgery, during or after chemotherapy with BV in patients with metastatic colorectal cancer (mCRC). METHODS: Detailed PubMed search in November 2009. RESULTS: Addition of BV to first- or second-line chemotherapy in patients with mCRC results in a statistically significant benefit in OS, PFS and RR. Addition of BV to chemotherapy causes no clinically relevant aggravation of SAE and seems safe with the primary tumor still in situ. The risk of emergency surgery due to BV-related SAE is estimated 2.0%. SAE rate is low if a time to surgery of 5-6 weeks is respected. The majority of SAE are wound healing complications. Bleeding and GI perforation occur infrequently, even following major surgery after BV-treatment. Major surgery during the course of BV-treatment results in an SAE rate of 1.3-2.7%. Postoperatively, a period of minimally 28 days should be respected before starting BV. CONCLUSION: Reported rates of BV-related SAE in relationship to surgery are low.

Radiofrequency ablation as a treatment tool for liver metastases of colorectal origin.

At diagnosis 10-25% of patients with colorectal liver metastases (CRLM) present as resectable disease. Liver resection is the gold standard treatment, resulting in a 5-year overall survival (OS) of 22-58%, local recurrence rates of 1.2-10.4% and a perioperative mortality of less than 5%. Multiple attempts have been made to assess the possible contribution of radiofrequency ablation (RFA) to improve OS and progression-free survival (PFS) in patients with unresectable colorectal liver metastases. The aim of this paper is to review the RFA literature in the setting of colorectal liver metastases: RFA with and without chemotherapy, RFA with and without resection, RFA for solitary unresectable CRLM, surgical and percutaneous imaging-guided RFA, RFA compared with chemotherapy. The reported OS, PFS, local recurrence rates, morbidity and mortality in these different settings are analyzed. This paper reflects on a possible role of RFA in resectable CRLM.

Circular 'superelastic' compression anastomosis: from the animal lab to clinical practice.

The recent development of a compression device using shape memory Nitinol technology to create an end-to-end anastomosis has renewed the interest in sutureless anastomotic techniques. A phase II, prospective open label clinical trial was started in May 2007 to evaluate the feasibility and safety of this new anastomotic device. Fourty patients who need left colectomy or high anterior resection for either diverticular disease or adenocarcinoma will be recruited in two academic hospitals (Uppsala,Sweden and Leuven, Belgium). Clinical leakage is the primary endpoint. Only preliminary results are available to date as the recruitment is ongoing. The median age of the first ten patients is 57.5 years (44-72). No anastomotic leakage occurred. The median hospital stay was 4.0 days. Only three patients noticed the passage of the ring through the anal canal. By three weeks no ring was sustained in the gastrointestinal tract as was objectified by plain X-ray. First clinical use of this new anastomotic device seems promising. Final results for the total phase II trial are awaited. A prospective randomized trial to compare the efficacy of the EndoCar 28 with conventional stapling should be the next step.

Morbidity and mortality of laparoscopic vs. open radiofrequency ablation for hepatic malignancies.

AIMS: Surgical radiofrequency ablation (RFA) of hepatic malignancies is associated with superior oncological outcome as compared to percutaneous RFA. The aim of this prospective non-randomized cohort study was to compare morbidity and mortality of laparoscopic (LRFA) vs. open (ORFA) radiofrequency ablation of liver cancer. METHODS: Between October 1999 and November 2006, RFA was performed in 154 consecutive patients (percutaneous 12, LRFA 93, ORFA 49) for a total of 291 hepatic tumours (HCC 81, colorectal metastases 157, other 53). Seventy-four patients simultaneously underwent additional surgery. Laparoscopic RFA was performed in 45/54 patients with HCC, and in 44/54 patients with cirrhosis. Laparotomy was performed in 14/22 patients who underwent simultaneous colorectal resection, and in 12/22 patients with hepatic resection. RESULTS: Postoperative complications occurred in 25 patients with subsequent mortality in 2. As compared with LRFA, ORFA was associated with significantly (p<0.01) higher intra-operative blood loss (median 20 (range 0-1700) vs. 10 (0-900) ml), longer duration of surgery (180 (25-440) vs. 75 (30-390) min), more postoperative complications (17 vs. 8), and longer postoperative hospital stay (8 (1-127) vs. 4 (1-51) d). According to the therapy-oriented severity grading system (TOSGS) classification, postoperative complications in the ORFA-group were more severe than those in the LRFA-group (p<0.01). These findings were consistent in patients without simultaneous colorectal and/or hepatic resection and in patients with liver tumours measuring 3cm or less. In univariate analysis the following factors were significantly (p<0.01) related to the presence of postoperative complications: simultaneous colorectal resection, laparotomy, duration of surgery, tumour location in right liver, liver segment 7 (p=0.01), absence of cirrhosis (p=0.02), liver segment 8 (p=0.03), and metastatic liver cancer (p=0.04). CONCLUSION: LRFA for hepatic malignancies seems preferable above ORFA, provided good patient selection, surgical expertise, and long-term oncological control.

Laparoscopic liver resection using radiofrequency coagulation.

BACKGROUND: The use of radiofrequency (RF) energy has been described to perform open liver resection safely and with minimal blood loss. Yet no data are available on the potential contribution of RF energy to the limitation of intraoperative blood loss during laparoscopic liver resection (LLR). The aim of this prospective, nonrandomized study was to investigate the potential contribution of RF energy to the limitation of intraoperative blood loss in patients undergoing LLR. METHODS: Forty-five patients [male/female ratio 22/23, age 57 years (26-80)] underwent LLR. Eleven benign and 47 malignant lesions (mostly colorectal metastases) were resected. Median number [1 (1-3)] and maximum diameter [40 mm (8-170)] of tumors as well as median tumor free margins [10 mm (1-30)] were comparable in patients undergoing LLR with (20 patients) or without (25 patients) RF-assistance. Thirty-eight minor (< or = 2 segments) and 9 major (> 3 segments) resections were performed. Eighteen patients simultaneously underwent additional surgery. RESULTS: No mortality occurred. Median intraoperative blood loss was 200 (5-4000) ml and was similar in patients undergoing LLR with or without RF-assistance. The type of surgical procedure was a determinant for the amount of intraoperative blood loss (p = 0.0002). Significant bleeding occurred from large hepatic vessels at major resections. Median operation time was 115 (45-360) minutes. RF-assistance didn't seem to reduce perioperative morbidity. CONCLUSIONS: LLR can be performed with minimal intraoperative blood loss, which is determined by the type of hepatectomy. Significant intraoperative bleeding occurs from large hepatic vessels during major resections. RF-assisted parenchymal transection in LLR doesn't seem to reduce blood loss, operation time, or perioperative morbidity.

Gastro-intestinal stromal tumour of the duodenum: extreme presentation in two cases.

Gastro-intestinal stromal tumours (GIST) are primary mesenchymal tumours arising from the gastro-intestinal tract. They are uncommon visceral tumours, preferentially located in the stomach and small intestine. The present paper will discuss the clinical presentation of GIST in a 32-year-old female (Case 1) and in a 72-year-old female (Case 2). In both cases the tumour is located in the duodenum which appears to be a rather unusual location (4%) for GIST. This work will illustrate that duodenal GIST can occur in extreme presentations, diverging from vague complaints to directly life threatening symptoms.