Axel Stang

A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases

AIM To evaluate the role of radiofrequency ablation (RFA) as treatment of colorectal cancer liver metastases (CLMs). METHOD A PubMed literature search for original articles published until August 2008 was performed. Studies with 40 patients, 18 month median follow-up and reported 3 year overall survival (OS) rates after RFA of CLM were selected for analysis. RESULTS Thirteen clinical series and 8 non-randomised comparative studies were analysed. Median progression free survival after RFA ranged between 6 and 13 months. Median and 5-year OS after RFA (RFA plus resection) ranged between 24-59 months and 18-40% (36-46 months and 27-30%). Comparative studies indicated significantly improved OS after RFA versus chemotherapy alone, RFA plus chemotherapy versus RFA alone and up-front RFA versus RFA following second-line chemotherapy. CONCLUSION Our findings support that RFA prolongs time without toxicity and survival as an adjunct to hepatectomy and/or chemotherapy in well-selected patients, but not as an alternative to resection.

Differentiation of benign from malignant focal splenic lesions using sulfur hexafluoride-filled microbubble contrast-enhanced pulse-inversion sonography.

OBJECTIVE The purpose of our study was to evaluate whether sonographic characterization of focal splenic lesions could be improved by using low mechanical index pulse-inversion sonography after sulfur hexafluoride-filled microbubble injection. MATERIALS AND METHODS One hundred forty-seven splenic lesions (68 benign, 79 malignant) in 147 patients (81 men, 66 women; mean age, 51 years) underwent baseline gray-scale sonography and sulfur hexafluoride-enhanced low-acoustic-power pulse-inversion sonography (mechanical index < 0.1). Two site investigators assessed in consensus lesion and splenic enhancement during arterial and parenchymal phases. Four readers (readers 1 and 2, blinded; and readers 3 and 4, unblinded to clinical data) independently reviewed baseline and contrast-enhanced sonograms and provided confidence rating for diagnosis of malignancy or benignancy. Accuracy, sensitivity, specificity, positive and negative predictive values, and areas under the receiver operating characteristic curves (A(z)) were calculated by considering biopsy results or splenectomy (51 patients) or CT or MR images followed by serial sonography 6-12 months apart (96 patients) as reference standards. RESULTS Benign lesions appeared predominately non- or isoenhancing relative to splenic parenchyma, whereas malignant lesions appeared predominately progressively hypoenhancing. For correct diagnosis of benignancy or malignancy, review of contrast-enhanced sonography after baseline sonography yielded significantly improved diagnostic performance (overall accuracy, 51%, 43%, 70%, and 74% before vs 83%, 81%, 92%, and 91% after contrast-enhanced sonography for readers 1, 2, 3, and 4; p < 0.05; respectively) and significantly improved diagnostic confidence (A(z), 0.770, 0.678, 0.900, and 0.917 before vs 0.935, 0.917, 0.984, and 0.959 after contrast-enhanced sonography for readers 1, 2, 3, and 4; p < 0.05; respectively). CONCLUSION Sulfur hexafluoride-filled microbubble-enhanced sonography improves characterization of focal splenic lesions with and without the availability of clinical data.

Real-time ultrasonography-computed tomography fusion imaging for staging of hepatic metastatic involvement in patients with colorectal cancer: initial results from comparison to US seeing separate CT images and to multidetector-row CT alone.

Objectives:To prospectively evaluate the role of real-time ultrasonography (US)-computed tomography (CT) fusion imaging (US-CT) in comparison with US seeing separate CT images (US + CT) and multidetector-row CT (MDCT) for the correct staging of hepatic metastatic involvement in patients with colorectal cancer. Methods:Sixty-four patients with newly diagnosed colorectal cancer and who were referred for abdominopelvic staging before primary tumor resection underwent same-day MDCT, US + CT, and US-CT. Examinations were evaluated on-site by 2 investigators in consensus. Investigators recorded the size and location of detected lesions on segmental liver maps, classified them as being benign, malignant, or indeterminate, and finally assessed the M stage of the liver as being M0, M1, or Mx (indeterminate). All patients underwent surgical exploration including intraoperative US. Reference standard diagnosis was based on findings at surgery, intraoperative US, histopathology, and MDCT follow-up imaging. Differences among investigated modalities were analyzed using McNemar′s test. Results:The reference standard verified 109 (45 ≤ 1 cm) hepatic lesions in 25 patients, including 65 (25 ≤ 1 cm) metastases in 16 patients (M1). Regarding the 45 ≤ 1 cm liver lesions, rates for detection were significantly higher (P < 0.05) for MDCT (80%, 36/45) and US-CT (77.8%, 35/45) than for US + CT (64.4%, 29/45); the rate for correct classification by US-CT (71.1%, 32/45) was significantly higher than for US + CT (48.9%, 22/45) and MDCT (31.1%, 14/45) (all P < 0.05). On patient-based analysis, specificity of MDCT (85.4%, 41/48) was significantly lower (P < 0.05) than for US-CT (97.9%, 47/48) and US + CT (93.7%, 45/48); the positive predictive value of MDCT (63.1%, 12/19) was not significantly different (P = 0.27) compared with US + CT (82.3%, 14/17) but significantly lower (P < 0.05) than for US-CT (93.7%, 15/16). In 13 patients (59 lesions) with only benign (stage M0) or coexistent benign and malignant lesions (stage M1), indeterminate lesion ratings and indeterminate liver stagings (Mx) occurred both significantly lower (P < 0.05) with US-CT (3.4%, 2/59; and 0%, 0/13) than with US + CT (11.9%, 7/59; and 23.1%, 3/13) or with MDCT (30.5%, 18/59; and 53.8%, 7/13). Conclusions:Based on these initial diagnostic experiences, complementary US-CT fusion imaging of small CT-indeterminate liver lesions may have value in staging patients with colorectal cancer, focusing on patients who were likely to harbor only benign or coexisting benign and malignant liver lesions and in whom change of M staging would change the clinical management.

Bilateral thalamic infarction after reinfusion of DMSO-preserved autologous stem-cells

Infusion of DMSO-preserved autologous stem cells is generally a safe procedure, but adverse reactions like nausea, vomiting, facial flushing and abdominal cramps are frequent [1 – 3]. Less commonly observed but more serious toxicities include cardiovascular complications like bradycardia and arrhythmia. Additionally, there have been case-reports of neurological events. Reported complications included seizures [4,5], global amnesia [6], cerebral infarctions [6,7] and leukencephalopathies [8,9]. We report a case of severe neurotoxicitiy after autografting of hematopoeitic stem cells with the acute development of bilateral thalamic infarction. A 62 year old male patient had a 1 year history of light-chain myeloma without response to three courses of adriamycin, dexamethasone (AD). He was now committed for high dose therapy with autologous stem cell transplantation and received one course of cyclophosphamide, adriamycin and dexamethasone for stem cell mobilization and apheresis. The peripheral blood stem cells (PBSC) were frozen in liquid nitrogen after addition of 10% DMSO. The patient received high-dose melphalan (200 mg m) and 2 days later his 105 ml PBSC-graft was reinfused over a period of 5 min. The infused amount of DMSO was 0.11 ml kg bodyweight of the patient, which is in the lower range of what is typically applied [3]. Pre-medication included prednisone (250 mg), clemastine (2 mg), ranitidine (300 mg) and hydrocodon (20 mg). Blood pressure and ECG were continuously recorded from the patient during the course of the infusion and 1 h thereafter. One hour after the infusion the patient developed dysarthria, ophthalmic deviation of the right eye laterally indicative of oculomotor nerve paresis and complained of blurred vision. Neurological examination revealed bilateral Babinsky’s signs. The patient’s alertness progressively deteriorated from somnolence to coma within 2 h and he developed non-reactive miosis. Though spontaneous urination occurred, the patient did not display obvious epileptic seizures or a tongue bite. EEG showed generalized pathology without focal abnormalities. Emergency CT-scan of the head on the same day did not show obvious pathology at this time and echocardiography showed normal cardiac function and excluded an open foramen ovale as a cause of a possible paradoxical embolization from aggregates in the stem cell preparation. The patient was transferred to the intensive care unit because of falling oxygen saturation, but he recovered spontaneously over the next few hours and mechanical ventilation was unnecessary. Blood chemistry, heart rate and blood pressure remained normal during the course of the reaction. On the next day, MRI-scans of the head were performed and showed bilateral thalamic signal enhancements indicative of fresh ischemic lesions with a central hemorrhage on the right side (Figure 1(a, b)). The patient rapidly improved clinically and was discharged 17 days later with only minor neurological sequelae like urine incontinence and slight dysarthria. A MRI-scan of the head performed 1 week (Figure 1(c, d)) and 4 weeks (Figure 1(e, f)) after the reinfusion confirmed bilateral thalamic infarction.

Hu-antibody positive limbic encephalitis in a patient with Hodgkin lymphoma

Paraneoplastic symptoms can manifest in a multitude of organ systems and can precede cancer diagnosis, accompany the acute disease or appear during remission. Paraneoplastic neurological syndromes may involve the peripheral nervous system (i.e. peripheral neuropathy) or the central nervous system [1,2]. Limbic encephalitis is a severe manifestation of central nervous system paraneoplastic disease and is most often associated with small cell lung cancer (SCLC) with the majority of patients being positive for Hu antibodies in the serum [3]. Hu antibodies can occasionally be detected in patients with limbic encephalitis in conjunction with neoplasms of other organs including the prostate, the gastrointestinal tract, the breast, the bladder, the pancreas and the ovary [4]. Although limbic encephalitis in association with Hodgkin lymphoma (sometimes called Ophelia syndrome) has been described in a number of cases [5–13], no defined antibodies could be identified in patients with this condition. We report to our knowledge the first case of limbic encephalitis with high serum titres of Hu antibodies in a patient with Hodgkin disease. The 61-year-old male patient was initially presented with a painless enlargement of a cervical lymph node. The mass was surgically resected and the histological examination yielded the diagnosis of Hodgkin lymphoma of the nodular sclerosing type. The patient was subsequently transferred to an oncological centre where the tumor staging was completed. Computed tomography of the neck, the chest and the abdomen revealed multiple cervical and abdominal enlarged lymph nodes and local infiltration of the clivus of the bony skull base without infiltration of the meninges or brain parenchyma. The patient appeared mentally unremarkable upon admission but after a few days he dramatically declined cognitively over the course of about 1 week. First apparent symptoms were sleeping disturbances with excessive sleepiness during daytime but agitation in the night. Within the next days, the patient completely lost orientation towards place and time and he no longer could tell where he was or which year/month/season it was. The patient was not able to follow simple commands, could not recall issues discussed shortly before or recognise members of the attending medical staff. Neurological examination revealed severe deficits in short-term memory and dementia resulting in severe cognitive impairment (Rankin score 5). The long-term memory seemed to be spared as he could recall details like his birth date or his former profession. No other neurological deficits were observed. Laboratory examination of the cerebrospinal fluid (CSF) did not show any abnormalities (normal cell count and no malignant cells, normal lactate, normal protein

Multi-omic based molecular profiling of advanced cancer identifies treatable targets and improves survival in individual patients

A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-generation sequencing and phosphoprotein profiling. Expression and phosphorylation of key oncogenic pathways were measured to identify targets at the (phospho-) proteomic level. At genomic level, 50 oncogenes and tumor suppressor genes were analyzed. Based on molecular profiling, targeted therapies were decided by the attending oncologist. Accordingly, 28 patients who met the defined criteria fell in two equal-sized groups. One group received targeted therapies while the other did not. Following six months of treatment, disease control was achieved by 49% of patients receiving targeted therapy (complete remission, 14%; partial remission, 21%; stable disease, 14%; disease progression, 36%; death, 14%) and 21% of patients receiving non-targeted therapy (stable disease, 21%; disease progression, 64%; death, 14%). Individual patients experienced dramatic responses to a therapy which otherwise would not have been applied. This approach clarifies the value of multi-omic molecular profiling for cancer diagnostics.