Genomic landscape of treatment refractory metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. MATERIAL AND METHODS: Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. RESULTS: A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (n = 72) of the patients. A total of 31.3% (n = 25) of the patients received therapy either as targetable therapy outside an available trial (n = 2), FDA approved therapy (n = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (n = 21). CONCLUSION: Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided interventions: General Aspects and EUS-guided Sampling (Short Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided Interventions: General aspects and EUS-guided sampling (Long Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V.

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V - EUS-Guided Therapeutic Interventions (short version).

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Short Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Long Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound (INVUS) assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, and safe and effective performance of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part I. General Aspects (Short Version).

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part I. General Aspects (long Version).

This is the first part of the Guidelines on Interventional Ultrasound of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and covers all general aspects of ultrasound-guided procedures (long version).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Short Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version/ short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part II. Diagnostic Ultrasound-Guided Interventional Procedures (Long Version).

This is the second part of the series on interventional ultrasound guidelines of the Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It deals with the diagnostic interventional procedure. General points are discussed which are pertinent to all patients, followed by organ-specific imaging that will allow the correct pathway and planning for the interventional procedure. This will allow for the appropriate imaging workup for each individual interventional procedure (Long version).

Microwave ablation of liver metastases guided by contrast-enhanced ultrasound: experience with 125 metastases in 39 patients.

PURPOSE: The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS). MATERIALS AND METHODS: 39 patients (17 women and 22 men) with a total of 125 liver metastases were treated with percutaneous or intraoperative CEUS-guided MW ablation. The primary tumor was colorectal cancer (n = 31), breast cancer (n = 6), carcinoid tumor (n = 1), and gastrointestinal stromal tumor (GIST) (n = 1). The median number of metastases ablated in the 45 treatment sessions was 2 (range 1 - 11). The median size (maximum diameter) of the 125 metastases was 1.5 cm (range, 0.6 - 4.0 cm). Nineteen (15 %) of the 125 metastases were bigger than 2 cm. Metastases smaller than 2 cm were treated with a single needle, metastases bigger than 2 cm were treated with 2 or 3 parallel needles. RESULTS: The 45 MW ablation sessions were performed percutaneously (n = 30), during laparotomy (n = 3), or during laparotomy combined with liver resection (n = 12). The 39 patients were followed up for at least 4 months with a median duration of 11 months (range, 4 - 20 months). The technical success rate was 100 %. The clinical effectiveness was 100 % with complete coverage of the metastasis by the avascular coagulation zone evaluated on immediate post-ablation CEUS. Local tumor progression (local recurrence) was seen in 12 (9.6 %) of the 125 treated metastases, and affected 10 (26 %) of the 39 patients. One major complication was observed in the form of a liver abscess that easily resolved after percutaneous drainage. Four minor complications were observed: Three cases of pain located at the puncture site and one case of ascites. CEUS was valuable in all phases of ablation including pre-ablation staging and procedure planning, placement of MW needles in the tumor, immediate post-ablation control of coagulation size, and finally in the long term follow-up regime. CONCLUSION: CEUS-guided MW ablation of liver metastases is an efficient and safe ablation technique with several advantages compared to other ablation modalities.

The loop electrode: in vitro evaluation of a device for ultrasound-guided interstitial tissue ablation using radiofrequency electrosurgery.

RATIONALE AND OBJECTIVES: I developed and tested in vitro a device for ultrasound-guided monopolar radiofrequency (RF) electrosurgical interstitial tissue ablation. METHODS: The current was applied to an electrode with a distal loop form (radius = 1 cm). The superelastic properties of the electrode allowed cannula introduction in the experimental medium (calf liver) before subsequent rotation of the electrosurgical cutting electrode, resulting in cutting off and isolation of a spherical lesion interstitially. The optimal setting of the RF unit and the optimal cutting speed were evaluated. Under ultrasonographic guidance and monitoring, approximately 150 lesions were produced with different loop designs and sizes. The gross appearance was evaluated and correlated to ultrasonography. RESULTS: An output effect of 200 W was optimal for resection and cutting with the loop electrode. An ellipsoid loop configuration could produce an almost spherical lesion with a diameter of 2.0 cm interstitially. Ultrasonography could guide the introduction of the loop electrode into tissue and visualize the upper part of the lesion. CONCLUSION: The loop electrode is a technique for percutaneous ultrasonographically guided tissue ablation. It was proved to be efficient in vitro by producing 2-cm liver lesions.

A cooled needle electrode for radiofrequency tissue ablation: thermodynamic aspects of improved performance compared with conventional needle design.

RATIONALE AND OBJECTIVES: I developed and tested a cooled needle electrode (CNE) for radiofrequency (RF) tissue ablation in vitro. METHODS: A 2-mm needle electrode with two lumina for internal water perfusion and irrigation of the needle tip and a conventional needle electrode were tested in ex vivo calf liver during different levels of output power (wattage). RF lesions produced by the two needle types were further evaluated with a thermal camera. RESULTS: When the CNE was used, a significant increase in the duration of ablation was observed, which caused a significant increase in delivered energy and lesion size when compared with the conventional needle electrode. The largest lesion produced with the CNE was almost spherical and measured 41 x 37 mm (longitudinal x transverse). The cooling effect was reflected in the image obtained with the thermal camera. CONCLUSION: This technique produced very large lesions compared with conventional methods and may have a role in many different kinds of RF needle ablation.

Radiofrequency tissue ablation with a cooled needle in vitro: ultrasonography, dose response, and lesion temperature.

RATIONALE AND OBJECTIVES: Radiofrequency (RF) tissue ablation with a cooled needle electrode (probe) can produce large lesions. By using this technique on ex vivo calf livers, the authors evaluated the role of ultrasound (US), dose response, and temperature course with time. METHODS: RF ablation was produced with a 14-gauge probe with a 2-cm exposed tip. The lesions were examined with US and macroscopically after various treatment durations. Tissue temperature was measured with thermosensors inserted 1, 2, and 3 cm from the probe. RESULTS: Before treatment the tip of the probe was easy to visualize with US, but treatment microbubbles obscured the lesion and probe. After treatment, the lesions appeared hypoechoic. Lesion size was underestimated based on US findings. Lesion size was logarithmically correlated to treatment duration. Lesion temperature increased at an increased rate with higher wattage applied and with decreased distance from the probe. CONCLUSION: US is useful for probe placement before treatment and might be of value after treatment. Lesion size increases reproducibility with treatment duration.

[Splenic infarction]. / Miltinfarkt.

Splenic infarction is a recognized sequel of a number of diseases but, until recently, it has been difficult to verify. Employing the new imaging techniques, the spleen has become diagnostically more accessible and increase in the number of splenic infarctions diagnosed must be anticipated. The commonest basic cause is cardiovascular disease but the etiology may be manifold. Whereas the infarct as such is of lesser significance, splenic abscess, eg after bacterial endocarditis, is a life-threatening condition. The treatment consists of surgical drainage and, frequently, splenectomy. The lethality is reduced from nearly 100% to approximately 10% when the correct treatment is employed.

[Color Doppler ultrasound. Principles, technique and clinical use possibilities]. / Farve-Doppler-ultralyd. Princip, teknik og kliniske anvendelsesmåder.

The medical ultrasound, the Doppler frequency shift is the difference between the frequency of the transmitted and reflected ultrasound. This is due a relative movement between the reflector (most frequently the red blood cells) and the ultrasound transducer. The ultrasound apparatus registers this difference in frequency and calculates the linear rate of flow employing the Doppler equation. The Doppler analysis is presented acoustically, graphically or by means of a colour code. In pulsed Doppler technique, conventional ultrasound scanning can be combined with Doppler analysis. Important indications are: differentiation between vascular and non-vascular structure, documentation of flow and determination of the direction of flow, diagnosis and quantitation of arterial stenoses and assessment of transplants.

[Urinary incontinence. Experiences with the artificial urethral sphincter AS 800]. / Urin-inkontinens. Erfaringer med artificiel uretral sphincter AS 800.

Since 1983, 62 patients with incontinence of urine (43 men and 19 women) were treated with an artificial sphincter model AS 800. During the period of observation, the artificial sphincters were removed in five patients on account of complications and six patients had died. In 22 patients, a total of 34 operations were required on account of complications. Out of 51 patients with artificial sphincters at the time of this review, 43 (84%) had experienced improvement: 15 (29%) were completely continent and 18 (35%) had only slight stress incotinence. It is concluded that the technical improvement which has taken place has improved the therapeutic results and approximately halved the number of complications requiring treatment.

[Epidermoid cyst of the testis]. / Epidermoidcyste i testis.

We report a case of epidermoid cyst of the testis. The condition is rare and benign. Conservative surgical treatment is advocated when the diagnosis is confirmed by histological frozen sections.