Performing Quality Control on Magnetic Resonance Imaging Liver Fat/Iron Quantification Studies: A Critical Requirement.

OBJECTIVE: Nonalcoholic fatty liver and iron overload can lead to cirrhosis requiring early detection. Magnetic resonance (MR) imaging utilizing chemical shift-encoded sequences and multi-Time of Echo single-voxel spectroscopy (SVS) are frequently used for assessment. The purpose of this study was to assess various quality factors of technical acceptability and any deficiencies in technologist performance in these fat/iron MR quantification studies. METHODS: Institutional review board waived retrospective quality improvement review of 87 fat/iron MR studies performed over a 6-month period was evaluated. Technical acceptability/unacceptability for chemical shift-encoded sequences (q-Dixon and IDEAL-IQ) included data handling errors (missing maps), liver field coverage, fat/water swap, motion, or other artifacts. Similarly, data handling (missing table/spectroscopy), curve-fit, fat- and water-peak separation, and water-peak sharpness were evaluated for SVS technical acceptability. RESULTS: Data handling errors were found in 11% (10/87) of studies with missing maps or entire sequence (SVS or q-Dixon). Twenty-seven percent (23/86) of the q-Dixon/IDEAL-IQ were technically unacceptable (incomplete liver-field [39%], other artifacts [35%], significant/severe motion [18%], global fat/water swap [4%], and multiple reasons [4%]). Twenty-eight percent (21/75) of SVS sequences were unacceptable (water-peak broadness [67%], poor curve-fit [19%] overlapping fat and water peaks [5%], and multiple reasons [9%]). CONCLUSIONS: A high rate of preventable errors in fat/iron MR quantification studies indicates the need for routine quality control and evaluation of technologist performance and technical deficiencies that may exist within a radiology practice. Potential solutions such as instituting a checklist for technologists during each acquisition procedure and routine auditing may be required.

Molecular characterization of scant lung tumor cells using iron-oxide nanoparticles and micro-nuclear magnetic resonance.

Advances in nanotechnology and microfluidics are enabling the analysis of small amounts of human cells. We tested whether recently developed micro-nuclear magnetic resonance (µNMR) technology could be leveraged for diagnosing pulmonary malignancy using fine needle aspirate (FNA) of primary lesions and/or peripheral blood samples. We enrolled a cohort of 35 patients referred for CT biopsy of primary pulmonary nodules, liver or adrenal masses and concurrently obtained FNA and peripheral blood samples. FNA sampling yielded sufficient material for µNMR analysis in 91% of cases and had a sensitivity and specificity of 91.6% and 100% respectively. Interestingly, among blood samples with positive circulating tumor cells (CTC), µNMR analysis of each patient's peripheral blood led to similar diagnosis (malignant vs benign) and differential diagnosis (lung malignancy subtype) in 100% and 90% (18/20) of samples, respectively. µNMR appears to be a valuable, non-invasive adjunct in the diagnosis of lung cancer. FROM THE CLINICAL EDITOR: The authors of this study established that recently developed micro-nuclear magnetic resonance (µNMR) technology can be leveraged for diagnosing pulmonary malignancy using fine needle aspirate (FNA) of primary lesions and/or peripheral blood samples derived from 35 patients, suggesting practical clinical applicability of this technique.

Factors affecting survival following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma.

PURPOSE: To assess factors associated with better overall survival (OS) and progression-free survival (PFS) following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma (HCC) MATERIALS AND METHODS: Data of 130 patients (104 men; median age, 62 y) with inoperable HCC who underwent successful DEB chemoembolization with 100-300 -µm LC Bead particles loaded with 50 mg doxorubicin per vial were reviewed following human research committee approval. Effects of various clinical, imaging, and response factors on OS and PFS were assessed by univariate Kaplan-Meier survival analysis. Multiple Cox regression with backward elimination was performed for terms found significant (P ≤ .05) on univariate analysis. RESULTS: The number of DEB chemoembolization procedures per patient ranged from one to four (mean, 2 ± 1). The median PFS and OS were 5.7 months (95% confidence interval, 4.6-7.6 mo) and 14.7 months (95% confidence interval, 12.3-19.7 mo), respectively. On multivariate Cox regression, Cancer of the Liver Italian Program (CLIP) score of 1 or lower, necrosis of more than 50%, and response or stable disease per Response Evaluation Criteria In Solid Tumors after DEB chemoembolization were associated with better PFS. CLIP score of 1 or lower, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or lower, absence of portal vein (PV) thrombosis, and necrosis greater than 50% following DEB chemoembolization were associated with better OS. CONCLUSIONS: CLIP score of 1 or lower and necrosis of more than 50% are independent variables affecting PFS and OS after DEB chemoembolization, whereas absence of PV thrombosis and ECOG PS of 1 or lower affected OS but not PFS.

Comparison of select cancer biomarkers in human circulating and bulk tumor cells using magnetic nanoparticles and a miniaturized micro-NMR system.

Circulating tumor cells (CTC) harvested from peripheral blood have received significant interest as sources for serial sampling to gauge treatment efficacy. Nanotechnology and microfluidic based approaches are emerging to facilitate such analyses. While of considerable clinical importance, there is little information on how similar or different CTCs are from their shedding bulk tumors. In this clinical study, paired tumor fine needle aspirate and peripheral blood samples were obtained from cancer patients during image-guided biopsy. Using targeted magnetic nanoparticles and a point-of-care micro-NMR system, we compared selected biomarkers (EpCAM, EGFR, HER-2 and vimentin) in both CTC and fine needle biopsies of solid epithelial cancers. We show a weak correlation between each paired sample, suggesting that use of CTC as "liquid biopsies" and proxies to metastatic solid lesions could be misleading. FROM THE CLINICAL EDITOR: In this clinical study, paired tumor fine needle aspirate and peripheral blood samples were obtained from patients with solid epithelial cancers during image-guided biopsy. Using targeted magnetic nanoparticles and a point-of-care micro-NMR system, the authors compared selected biomarkers in both circulating tumor cells (CTC) and fine needle biopsies, demonstrating a weak correlation between each paired sample, suggesting that use of CTC could be misleading in this context.

Gastrointestinal malignancies in pregnancy.

Gastrointestinal malignancies, though uncommon in pregnancy, present several unique challenges with regards to diagnosis, staging, and treatment. Imaging the pregnant patient with a suspected or confirmed GI malignancy requires modifications to the radiologic modality of choice and protocol in order to minimize harm to the fetus, ensure accuracy in diagnosis and staging and guide treatment decisions. In this review article, we discuss the imaging approach to the pregnant patient with GI cancer, including safe radiologic modalities and modifications to imaging protocols. We also review the most common GI cancers encountered in pregnancy, including colorectal, pancreatic, gastric, and small bowel tumors, with emphasis to imaging findings, staging, and treatment considerations.

Aberrant Vascular Anatomy Associated With Artifactual Focal Avidity in the Liver on PSMA PET.

ABSTRACT: 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT is a valuable tool for staging and restaging of prostate cancer. Prostate-specific membrane antigen expression is not specific to prostate cancer, as it is expressed in normal tissues as well as in neoplastic and nonneoplastic processes. Awareness of the broad possibility of lesions with PSMA avidity is necessary to recognize normal variants and avoid potential pitfalls in image interpretation. We present a series of cases showing physiologic focal PSMA avidity in hepatic segment IVb. We correlate this uptake with aberrant hepatic vasculature. The awareness of this variant is important for accurate image interpretation to prevent additional invasive procedures, undue treatment escalation, and denial of curative treatment to patients.

Successful Liver Transplantation of Recurrent Fibrolamellar Carcinoma following Clinical and Pathologic Complete Response to Triple Immunochemotherapy: A Case Report.

INTRODUCTION: Fibrolamellar carcinoma (FLC) is a rare liver cancer that predominantly affects younger patients without a history of liver disease. Surgical resection is the cornerstone of therapy and represents the best potentially curative treatment option. Modest objective responses with cytotoxic chemotherapy alone or combined with immune checkpoint inhibitors (ICIs) have been reported; however, there are no established systemic therapy regimens for unresectable or metastatic FLC. CASE PRESENTATION: We report a case of a 23-year-old woman with FLC who presented with a 11.5 × 8.3 cm left liver mass and subsequently underwent resection as initial therapy. Molecular analysis of her surgical tissue revealed a DNAJB1-PRKACA fusion gene. The patient developed biopsy-proven recurrent FLC with multiple liver lesions but without any distant metastatic disease only 3 months after initial resection. In light of emerging data, the patient was treated with a novel triple therapy regimen including 5-fluorouracil (5-FU), interferon (IFN) alfa-2b, and nivolumab. Partial radiographic response was achieved after 4 treatments and complete response was achieved after 12 cycles with the combination. The patient received 2 more doses of 5-FU/IFN alfa-2b without nivolumab and underwent orthotopic liver transplantation (OLT) 6 months after the last dose of ICI. Pathological examination of the explanted liver remarkably confirmed pathologic complete response. She remains recurrence-free and is on active surveillance. DISCUSSION/CONCLUSION: For patients with unresectable/recurrent FLC with no distant disease, the combination of 5-FU, IFN alfa-2b, and nivolumab could be an effective systemic therapy option. The use of this chemoimmunotherapy regimen to downstage FLC prior to OLT may be worth investigating further.

Diabetes revealed: multisystem danger.

OBJECTIVE: The purpose of this article is to review the role of diagnostic imaging in the evaluation of women with diabetes. CONCLUSION: Diabetic patients present a challenging population for the performance of various imaging studies and special considerations need to be made to obtain adequate studies. Imaging plays a significant role in assessing the multisystem morbidity of diabetes. Furthermore, diabetes in women may have some unique features and consequences and imaging studies can aid in the correct management of these patients.

The management of stage I nonseminomatous testicular germ cell tumors.

Testicular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis. Lymphovascular invasion, embryonal-cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic diseasein stage I NSGCT. Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin-based chemotherapy. All available treatment modalities produce excellent results, with a long-term survival of almost 100%. Consequently, therapy-induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile as well as the patient's preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer.

Dermatomyositis associated with breast cancer.

An increased risk of underlying malignancy has been found in patients with dermatomyositis (DM). The risk is increased even in patients with DM aged 45 or younger and remains high for many years after diagnosis. Breast carcinoma does not represent the most common solid tumor associated with this autoimmune disorder. In the present report, two new cases of DM associated with breast cancer are described, together with an extensive literature review.

Two cycles of carboplatin-based adjuvant chemotherapy for high-risk clinical stage I and stage IM non-seminomatous germ cell tumours of the testis: a HECOG trial.

BACKGROUND: We investigated the efficacy and safety of 2 cycles of adjuvant chemotherapy with carboplatin, etoposide and bleomycin (CEB90) in patients with high-risk clinical stage I or stage IM non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: A total of 52 consecutive patients (22 patients with high-risk histological features [vascular invasion, presence of embryonal carcinoma, absence of yolk sac tumour] and 30 with tumour marker activity post-orchidectomy-stage IM) were entered into this prospective study. Chemotherapy consisted of carboplatin 400 mg/m2 or AUC 5 (day 1), etoposide 165 mg/m2 (days 1-3) and bleomycin 30 mg (days 1, 8, 15). Chemotherapy was repeated every 3 weeks. RESULTS: During a median follow-up of 112 months (range, 10 to 174 months), two patietns with stage IM relapsed. These cases had a disseminated, marker-positive germ cell tumour (GCT), extensively involving both liver and lungs in the first case and para-aortic lymph nodes and lung in the second one; both patients died of the tumour after a number of salvage chemotherapy (including high-dose therapy) regimens. Fifty patients (96%) are alive and disease-free. Two cycles of CEB90 were well tolerated and the only side-effects were myelotoxicity and alopecia. CONCLUSION: Despite the general consensus that ciplatin-based chemotherapy is superior to carboplatin-containing regimens in testicular cancer, 2 cycles of CEB90 may be an equally effective treatment option as adjuvant therapy for high-risk clinical stage I and IM patients.

Safety and effectiveness of chemoembolization with drug-eluting beads for advanced-stage hepatocellular carcinoma.

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, patients with advanced stage (BCLC-C) hepatocellular carcinoma (HCC) are recommended for systemic treatment or palliative therapy. However, chemoembolization with drug-eluting beads (DEB-TACE) has been shown to be safe in high-risk patients. The purpose of our study was to evaluate the safety and effectiveness of DEB-TACE in patients with an advanced-stage HCC. METHODS: In this institutional review board-approved, retrospective study, 80 patients with advanced-stage HCC underwent DEB-TACE with doxorubicin. Patients were evaluated for median hospital stay, incidence of Grade 3/4 toxicities, 30-day mortality, progression-free survival (PFS), and overall survival (OS) following DEB-TACE. Univariate and multivariate analysis were performed for predictors of better OS. RESULTS: The median hospital stay following DEB-TACE was 1 day (range: 1-11). The median PFS and OS were 5.1 months [95% confidence interval (CI): 4.1-7.7] and 13.3 months (95% CI: 10.1-18.6) respectively. On multivariate analysis ECOG PS ≤ 1 and >2 DEB-TACE procedures were associated with better OS. Patients with ECOG PS ≤ 1 demonstrated a median survival of 17.7 months compared with 5.6 months for patients with ECOG PS > 1 (p = 0.025). Multiple DEB-TACE procedures (>2 procedures) were associated with improved survival (26.8 months) compared with patients with one or two procedures (11.4 months, p = 0.01). Portal vein thrombosis or extrahepatic disease had no statistically significant association with OS. CONCLUSIONS: DEB-TACE is safe and effective in patients with advanced HCC. ECOG PS ≤ 1 and >2 DEB-TACE procedures were associated with better OS.

Brain metastases from epithelial ovarian cancer: a review of the literature.

BACKGROUND: Brain metastases from epithelial ovarian cancer (EOC) are rare. This report is based on a review of the literature. METHODS AND RESULTS: This review summarizes the incidence, clinical features, pathophysiology, and diagnostic evaluation of EOC. The section on current treatment includes a thorough evaluation of the literature, highlights controversies over treatment options, and provides insight into novel approaches. Current treatment options include surgical resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery, and chemotherapy. Corticosteroids and anticonvulsant medications are commonly used for the palliation of mass effects and seizures, respectively. In the reviewed series, a better outcome was seen following surgical resection and WBRT with or without chemotherapy for solitary and resectable brain metastases. CONCLUSION: The prognosis for patients with brain metastases from EOC is poor. A better outcome might be obtained using multimodality therapy. Because of the small number of patients included in the reported studies, multicenter clinical trials are needed for further investigation in order to critically evaluate the clear benefit of these treatment options in selected patients.

Adjuvant and neoadjuvant chemotherapy in muscle invasive bladder cancer: literature review.

Radical cystectomy is the standard treatment for patients with clinically localized muscle invasive bladder cancer, providing a 5-year survival rate of approximately 50%. Failure to cure is often due to the presence of occult metastases beyond the margins of local therapy, indicating a need for eradication of micrometastatic disease with systemic treatment, in order to improve survival. Combined chemotherapy regimens, such as methotrexate-vinblastine-cisplatin (CMV), methotrexate-vinblastine-cisplatin-doxorubicin (M-VAC) and gemcitabine-cisplatin (GC) have already demonstrated their effectiveness in patients with advanced or metastatic disease and have been considered as appropriate regimens in the peri-operative setting. Large randomized studies with a prolonged follow-up have been able to confirm a modest survival benefit with neoadjuvant therapy. A recent meta-analysis, including all previous reported randomized trials, concluded that neoadjuvant chemotherapy administration provides a significant survival benefit and can be administered without adverse outcomes resulting from delayed local therapy. Adjuvant chemotherapy trials, although promising, have failed to show statistically improved survival, mostly due to small sample sizes and absent or inconclusive data on overall survival. A multi-center randomized-controlled trial is currently ongoing, in order to elucidate the role of post-operative chemotherapy administration.

Recent advances in conventional-dose salvage chemotherapy in patients with cisplatin-resistant or refractory testicular germ cell tumors.

Testicular germ cell tumors represent the most frequent malignancy in young males aged 20-35 years. Despite the considerably high cure rates provided by platinum-based chemotherapy, 20-30% of cases with advanced disease do not achieve a long-term disease-free survival with first-line chemotherapy. These patients are candidates for conventional-dose or high-dose salvage chemotherapy. The current conventional-dose salvage regimens of reference are the vinblastine-ifosfamide-cisplatin or etoposide-ifosfamide-cisplatin combinations, which are expected to cure approximately 25% of non-seminomatous germ-cell tumour patients. Paclitaxel has also been proved effective both as monotherapy in heavily-pretreated cases and as part of first-line salvage regimens; the combination of paclitaxel-ifosfamide-cisplatin, followed or not by high-dose chemotherapy, induced a favorable long-term disease-free survival rate, especially in patients with good prognosis. Newer cytotoxic drugs, such as gemcitabine and oxaliplatin have also been proved effective, while other agents, such as temozolamide, or targeted therapies, such as trastuzumab in cases over-expressing HER2/neu (20% of relapsing germ-cell tumors) are currently under evaluation. Seminomas have generally a better prognosis than non-seminomatous tumors and salvage therapy is expected to cure about 50% of all cases.

Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy.

OBJECTIVE: To investigate the impact of bleomycin-etoposide-carboplatin combination chemotherapy on long-term fertility in patients with testicular germ cell tumors. METHODS: Twenty-five patients with high risk stage I and IM non-seminomatous germ cell tumors (NSGCT, Group A) and 44 with advanced seminoma or NSGCT (Group B) were treated with bleomycin 30 mg (days 2, 9, 16), etoposide 165 mg/m(2) (days 1-3) and carboplatin 400mg/m(2) or AUC 5 (day 1) (BEC(90)). Treatment was repeated every 3 weeks. Group A patients received 2 cycles of BEC(90), while Group B ones received 4 to 5 cycles of BEC(90). Sperm count and hormonal analyses were examined pre- and post-chemotherapy. Counts were classified as normospermia (NS) if >20 x 10(6)ml(-1), oligospermia (OS) if 1-20 x 10(6)ml(-1) and azoospermia (AS) if <1 x 10(6)ml(-1). RESULTS: Patients were followed for a median of 2.9 years post-chemotherapy. The post-orchidectomy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit while the serum levels of follicle stimulating hormone (FSH) and testosterone (T) were within the reference interval. Thirty-eight (55%) patients had NS pre-chemotherapy. None of the 14 NS patients who received 2 cycles of BEC(90) had AS post-chemotherapy, while only 1 of the 24 NS patients who were treated with > or =4 cycles of BEC(90) had AS post-treatment. Among the NS patients, 93% and 83%, respectively, remained NS following chemotherapy. Overall, 90% of patients had recovery (61% NS, 29% OS) of spermatogenesis after treatment. The median FSH serum values were significantly elevated at least 1-year post-chemotherapy when compared with the pre-treatment levels. Eighteen months post-chemotherapy the median FSH values had returned to the reference limits. Serum LH and T levels were unaffected by treatment. The pre-treatment sperm count and the bulk of disease were significantly associated with recovery of spermatogenesis. No association was found between recovery of spermatogenesis and 2 or > or =4 cycles of chemotherapy, age > or =30 years and post-chemotherapy lymph node dissection. Thirteen patients (4 with OS) fathered 16 children. No congenital abnormalities occurred in any of these children. CONCLUSION: The BEC(90) regimen has no major effect on fertility and Leydig cell function. However, carboplatin-based chemotherapy has been proved less effective than cisplatin-based chemotherapy and is not currently used in the treatment of testicular cancer.

Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor as third-line treatment in relapsed or cisplatin-refractory germ-cell tumor patients: a phase II study.

OBJECTIVE: To investigate the efficacy and tolerability of the combination of oxaliplatin and irinotecan in patients with relapsed or cisplatin-refractory germ cell tumors (GCT). PATIENTS AND METHODS: Eighteen patients with relapsed or cisplatin-refractory GCT were treated with oxaliplatin 85 mg/m(2) on days 1 and 15, followed by irinotecan 80 mg/m(2) on days 1, 8 and 15, every four weeks for a maximum of six cycles. RESULTS: All patients were assessable for response and toxicity. Overall, 7 patients (40%) achieved a favorable response (4 complete and 3 partial responses). One of the complete responders relapsed after 2.5 months and despite further treatment with high dose chemotherapy, he died two months later. The remaining 3 patients are continuously disease free for 11+, 14+ and 19+ months. The partial responders subsequently progressed and died after 2, 3 and 4.5 months, respectively. None of the patients with extragonadal mediastinal GCT responded to oxaliplatin and irinotecan chemotherapy. The investigated combination has a good tolerance. Neutropenia related toxicity (grade 3/4, 17%), neutropenic infections and sepsis were not common probably due to prophylactic use of hematopoietic colony stimulating factor (G-CSF). Thrombocytopenia and anemia were not a serious problem. Gastrointestinal side effects, specifically grade 3/4 diarrhea and nausea/vomiting were noted in 22% and 28% of patients, respectively. Oxaliplatin-associated neurotoxicity was rather low; grade 3 peripheral sensory neuropathy was recorded in 11% of patients. CONCLUSION: The combination of oxaliplatin and irinotecan is feasible and associated with significant clinical antitumor activity, mild and manageable toxicity and easy outpatient administration in patients with relapsed or cisplatin-refractory germ cell cancer. This combination seems to offer a possibility for long-term disease-free status (17%), despite the poor prognostic features of the study patient group.

Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study.

OBJECTIVE: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluoruracil (5-FU) and high-dose leucovorin (LV) (FOLFOX-4) in patients with platinum-resistant, taxane-pretreated recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients, with a median age of 58 years (range 33-77), were treated with oxaliplatin 85 mg m(-2) as a 2-h infusion on day 1, LV 200 mg m(-2) day(-1) as a 2-h infusion followed by bolus 5-FU 400 mg m(-2) day(-1) and a 22-h infusion of 5-FU 600 mg m(-2) day(-1) for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. RESULTS: The vast majority of patients had performance status 0 or 1 and 76.3% had > or = 2 metastatic sites. A median number of four cycles per patient (range, 1-8) were administered. Based on an intention-to-treat analysis, 3 patients (7.9%) achieved a complete response (CR) and 8 (21.1%) achieved a partial response (PR), for an overall response rate of 29%. Another 29% of patients had stable disease (SD). The median relapse-free survival was 5.2 months (range 2.5-17), the median time to tumor progression was 4.8 months (range 0.6-19), and the median overall survival was 10.1 months (range 0.2-36). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 29% and 21.1% of patients, respectively. Febrile neutropenia was encountered in 3 patients (7.9%), who were successfully treated. Grade 3/4 neurotoxicity developed in 15.8% of patients; neurotoxicity gradually declined after treatment discontinuation. Alopecia, nausea-vomiting, diarrhea, mucositis, and asthenia were not a serious problem. There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin and 5-FU/LV (FOLFOX-4) appears to be an effective regimen with a good toxicity profile for the treatment of platinum-resistant, taxane-pretreated ovarian cancer.