Clinical routine use of virtual monochromatic datasets based on spectral CT in patients with hypervascularized abdominal tumors - evaluation of effectiveness and efficiency.

BACKGROUND: Virtual monochromatic images (VMI) generated using spectral computed tomography (CT) are promising recently available tools to improve diagnostic performance in oncologic patients. PURPOSE: To investigate if virtual monochromatic datasets are suitable for clinical routine use in patients with hypervascularized abdominal tumors. MATERIAL AND METHODS: A total of 41 patients with hypervascularized hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), or neuroendocrine tumors (NET) were enrolled in the study; 451 CT series were analyzed. In an intra-individual study design, virtual monochromatic datasets of the arterial phase of each scan were computed. Image quality was assessed objectively by determining signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR) and subjectively by using five-point Likert-scales. The volume CT dose index (CTDIvol) was taken from each radiation dose report. The increase in reading time was estimated from the increase in the number of images. RESULTS: Intra-individual comparison of the spectral mode in the arterial phase with the portal venous phase revealed no significant increase in the applied dose. SNR, CNRtumor-to-liver , and CNRtumor-to-muscle were significantly increased by lowering virtual monochromatic energy. Subjective image quality scores revealed an increase of contrast in low energy datasets, resulting in significantly higher diagnostic confidence, but an increased image noise at low energies. While diagnostic confidence improved, taking all datasets into account resulted in a significantly longer estimated reading time. CONCLUSION: In clinical practice, the use of low energy VMI improved diagnostic confidence without a significant increase in dose. The main disadvantage is a decrease in efficiency due to longer reading times.

[Vascular Complications and Emergencies within Oncologic Abdominal Surgery - What Knowledge and Skills Are Essential for the Visceral Surgeon]. / Vaskuläre Komplikationen und Notfälle in der onkologischen Viszeralchirurgie ­ was muss ein Viszeralchirurg können und wissen.

Background Continuous improvements in perioperative and neoadjuvant therapy concepts nowadays permit more extensive tumor resections with curative intention. In patients with arterial or venous tumour involvement in preoperative imaging, physicians with expertise in vascular surgery should be involved in the planning phase of the operation. Unexpected vascular complications during abdominal surgery demand prompt management by the oncological surgeon. However, skills in vascular surgery are still not obligatory for the visceral surgeon in training. This topic is controversial and is therefore the focus of the present study. Patients and Methods From 2010 - 2015, a total of 126 patients underwent visceral operations involving vascular surgical interventions. Of these, 30 operations were performed as radical tumour resections. Retrospective data acquisition was performed with a minimum follow-up of 12 months. Aside from comprehensive characterisation of patients and their diseases, an outcome analysis was conducted. Furthermore, visceral surgery training programs in accordance with all 17 German federal medical associations were analysed and compared with respect to vascular surgery teaching. Results Vascular surgery was necessary in most patients, due to lesions of the mesentericoportal venous system (n = 11; 37%) and visceral arteries (n = 14; 47%). Techniques involved were mostly vascular sutures, reanastomosis or patch plastic surgery (n = 19; 63%) and venous thrombectomy/arterial embolectomy (n = 18; 60%). Hospital mortality was 3%. During follow-up, 33% of oncological patients died, whereas solely venous injury was an independent adverse prognostic variable (arterial vs. venous complications: HR 0.028; 95%-CI 0.002 - 0.442; p = 0.01). Skills in vascular surgery are optional for up to 12 months within visceral surgery training. Conclusions Intraoperative vascular complications in visceral surgical oncology are rare but pose severe risks for the patients. Their management requires basic knowledge and skills in vascular anatomy, preparation and skills to ensure immediate safe control of bleeding, as well as suture techniques and interposition grafts. Current training and specialisation in visceral surgery does not include obligatory vascular surgery teaching, so that this issue needs reevaluation.

Radiological features of primitive neuroectodermal tumors in intra-abdominal and retroperitoneal regions: A series of 18 cases.

OBJECTIVES: To characterize the imaging and clinicopathological features of primitive neuroectodermal tumors (PNETs) arising in intra-abdominal and retroperitoneal regions. METHODS: Eighteen patients with histopathologically proven intra-abdominal and retroperitoneal PNET were enrolled; computed tomography was performed for all cases, and magnetic resonance imaging was performed for a single case. Typical computed tomography and magnetic resonance imaging findings, including morphology, texture and enhancement features, as well as clinicopathological characteristics and prognosis data were retrospectively analyzed. RESULTS: Of eighteen PNET patients, fifteen were male and three were female, with a median age of 36 years (range, 2-65 years). The onset of symptoms was most often nonspecific and insidious. The mean tumor diameter was 7.2 cm (range, 3.0-12.1 cm), with necrosis in fifteen cases, cystic changes in eight, partition structure in five, calcification in five, hemorrhage in two, and mural nodules in one. Contrast enhanced computed tomography showed multiple tiny feeding arteries within the masses in six cases, resulting in a crab-like appearance, and mild ring enhancement pattern in five cases. Eleven cases showed surrounding invasion and metastasis. Of the eighteen PNET cases, nine cases showed smooth, well-defined margins, and nine cases had irregular, ill-defined margins. A median survival was 10.0±1.6 months. However, chemotherapy had efficacy on patients even those with advanced disease. CONCLUSIONS: Primary intra-abdominal and retroperitoneal PNETs are rare, and imaging features documented here may help the diagnosis of this severe disease. Notably, two signs present in retroperitoneal PNET tumors, including a mild ring enhancement pattern and a crab-like appearance of the tiny feeding arteries, may have the potential to help us improve the ability to make a relatively reliable diagnosis.

Assessment of repeatability and treatment response in early phase clinical trials using DCE-MRI: comparison of parametric analysis using MR- and CT-derived arterial input functions.

OBJECTIVES: Pharmacokinetic (PK) modelling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data requires a reliable measure of the arterial input function (AIF) to robustly characterise tumour vascular properties. This study compared repeatability and treatment-response effects of DCE-MRI-derived PK parameters using a population-averaged AIF and three patient-specific AIFs derived from pre-bolus MRI, DCE-MRI and dynamic contrast computed tomography (DC-CT) data. METHODS: The four approaches were compared in 13 patients with abdominal metastases. Baseline repeatability [Bland-Altman statistics; coefficient of variation (CoV)], cohort percentage change and p value (paired t test) and number of patients with significant DCE-MRI parameter change post-treatment (limits of agreement) were assessed. RESULTS: Individual AIFs were obtained for all 13 patients with pre-bolus MRI and DC-CT-derived AIFs, but only 10/13 patients had AIFs measurable from DCE-MRI data. The best CoV (7.5 %) of the transfer coefficient between blood plasma and extravascular extracellular space (K (trans)) was obtained using a population-averaged AIF. All four AIF methods detected significant treatment changes: the most significant was the DC-CT-derived AIF. The population-based AIF was similar to or better than the pre-bolus and DCE-MRI-derived AIFs. CONCLUSIONS: A population-based AIF is the recommended approach for measuring cohort and individual effects since it has the best repeatability and none of the PK parameters derived using measured AIFs demonstrated an improvement in treatment sensitivity. KEY POINTS: • Pharmacokinetic modelling of DCE-MRI data requires a reliable measure of AIF. • Individual MRI-DCE-derived AIFs cannot reliably be extracted from patients. • All four AIF methods detected significant K (trans) changes after treatment. • A population-based AIF can be recommended for measuring cohort treatment responses in trials.

Value of tumor vessel sign in isolated circumscribed hypervascular abdominopelvic mesenchymal tumors on multidetector computed tomography.

OBJECTIVE: The objective was to determine the usefulness of the tumor vessel sign for differentiating the groups of circumscribed hypervascular abdominopelvic mesenchymal tumors. METHODS: We enrolled a total of 4 groups such as patients with gastrointestinal stromal tumor (GIST) (26 patients), those with paraganglioma (9 patients), those with primary sarcomas (13 patients, excluding those with liposarcoma), and those with desmoid tumor (6 patients). The reviewers evaluated the presence of tumor vessels capable of directly tracing from the tumor margin to the named vessels. RESULTS: Twenty-five of 26 GIST cases, all of the paragangliomas, all of the primary sarcomas, and all of the desmoid tumors showed a positive sign. For the sign confirming GIST, the sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 96.2%, 100%, 100%, 96.6%, and 98.1%, respectively. The values of the area under the receiver operating characteristic curve have good or excellent diagnostic accuracies. CONCLUSIONS: The presence of the sign is considered to be helpful for differentiating the 4 groups of tumors.

ß-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma.

BACKGROUND: The use of ß-blockers for the management of hypertension has been recently associated with significant clinical benefits in cancer patients. Herein, we investigated whether ß-blockers could be used in combination with chemotherapy for the treatment of neuroblastoma. METHODS: Seven ß-blockers were tested for their antiproliferative and anti-angiogenic properties alone, and in combination with chemotherapy in vitro; the most potent drug combinations were evaluated in vivo in the TH-MYCN mouse model of neuroblastoma. RESULTS: Three ß-blockers (i.e., carvedilol, nebivolol and propranolol) exhibited potent anticancer properties in vitro and interacted synergistically with vincristine, independently of P-glycoprotein expression. ß-blockers potentiated the anti-angiogenic, antimitochondrial, antimitotic and ultimately pro-apoptotic effects of vincristine. In vivo, ß-blockers alone transiently slowed tumour growth as compared with vehicle only (P<0.01). More importantly, when used in combination, ß-blockers significantly increased the tumour regression induced by vincristine (P<0.05). This effect was associated with an increase in tumour angiogenesis inhibition (P<0.001) and ultimately resulted in a four-fold increase in median survival, as compared with vincristine alone (P<0.01). CONCLUSION: ß-blockers can increase treatment efficacy against neuroblastoma, and their combination with chemotherapy may prove beneficial for the treatment of this disease and other drug-refractory cancers.

Heterozygous inactivation of tsc2 enhances tumorigenesis in p53 mutant zebrafish.

Tuberous sclerosis complex (TSC) is a multi-organ disorder caused by mutations of the TSC1 or TSC2 genes. A key function of these genes is to inhibit mTORC1 (mechanistic target of rapamycin complex 1) kinase signaling. Cells deficient for TSC1 or TSC2 have increased mTORC1 signaling and give rise to benign tumors, although, as a rule, true malignancies are rarely seen. In contrast, other disorders with increased mTOR signaling typically have overt malignancies. A better understanding of genetic mechanisms that govern the transformation of benign cells to malignant ones is crucial to understand cancer pathogenesis. We generated a zebrafish model of TSC and cancer progression by placing a heterozygous mutation of the tsc2 gene in a p53 mutant background. Unlike tsc2 heterozygous mutant zebrafish, which never exhibited cancers, compound tsc2;p53 mutants had malignant tumors in multiple organs. Tumorigenesis was enhanced compared with p53 mutant zebrafish. p53 mutants also had increased mTORC1 signaling that was further enhanced in tsc2;p53 compound mutants. We found increased expression of Hif1-α, Hif2-α and Vegf-c in tsc2;p53 compound mutant zebrafish compared with p53 mutant zebrafish. Expression of these proteins probably underlies the increased angiogenesis seen in compound mutant zebrafish compared with p53 mutants and might further drive cancer progression. Treatment of p53 and compound mutant zebrafish with the mTORC1 inhibitor rapamycin caused rapid shrinkage of tumor size and decreased caliber of tumor-associated blood vessels. This is the first report using an animal model to show interactions between tsc2, mTORC1 and p53 during tumorigenesis. These results might explain why individuals with TSC rarely have malignant tumors, but also suggest that cancer arising in individuals without TSC might be influenced by the status of TSC1 and/or TSC2 mutations and be potentially treatable with mTORC1 inhibitors.

Molecular oxygen sensing: implications for visceral surgery.

BACKGROUND: Since mammalian cells rely on the availability of oxygen, they have devised mechanisms to sense environmental oxygen tension, and to efficiently counteract oxygen deprivation (hypoxia). These adaptive responses to hypoxia are essentially mediated by hypoxia inducible transcription factors (HIFs). Three HIF prolyl hydroxylase enzymes (PHD1, PHD2 and PHD3) function as oxygen sensing enzymes, which regulate the activity of HIFs in normoxic and hypoxic conditions. Many of the compensatory functions exerted by the PHD-HIF system are of immediate surgical relevance since they regulate the biological response of ischemic tissues following ligation of blood vessels, of oxygen-deprived inflamed tissues, and of tumors outgrowing their vascular supply. PURPOSE: Here, we outline specific functions of PHD enzymes in surgically relevant pathological conditions, and discuss how these functions might be exploited in order to support the treatment of surgically relevant diseases.

Angiogenin up-regulation correlates with adverse clinicopathological and biological factors, increased microvascular density and poor patient outcome in neuroblastomas.

AIMS: As new biomarkers are urgently needed to identify children with high-risk neuroblastoma (NB), we studied the contribution of angiogenin (ANG) to angiogenesis and its association with clinicopathological and biological features and patient outcome in NB. METHODS AND RESULTS: Ninety NBs and 12 ganglioneuromas (GNs) were immunostained for ANG and CD31. ANG expression in NB tumoral cells (ANG scores) and vessels [ANG microvascular density (MVD)] and total MVD (CD31 MVD) were determined. The ANG score was significantly greater in NBs than in GNs (P = 0.015) and in NBs from children with stage 4 tumours, high-risk disease, unfavourable pathology (P < 0.001 for each), MYCN amplification (P = 0.003), and 1p deletion (P = 0.002). ANG scores correlated with ANG MVD and CD31 MVD (P < 0.001 for each). Total ANG and CD31 protein levels, measured with a sensitive enzyme-linked immunosorbent assay, were highly correlated (P = 0.003). High ANG scores were associated with decreased overall and event-free survival (log-rank test, P = 0.025 and P = 0.018, respectively). High ANG MVD was associated with decreased overall and event-free survival (log-rank test, P = 0.009 and P = 0.026, respectively). High CD31 MVD was associated with decreased event-free survival (P = 0.045). CONCLUSIONS: The strong correlation of ANG up-regulation with total MVD and adverse clinicopathological and biological factors indicates that ANG supports growth and progression in NB.

Depiction of variants of the portal confluence venous system using multidetector row CT: analysis of 916 cases.

PURPOSE: Detailed knowledge of the venous mesenteric system is important for gastrointestinal surgery, particularly for transplantation planning and surgery and for the comprehension of perioperative complications that may influence patient outcome. Data about the mesenteric venous anatomy in the literature varies substantially. The purpose of this study was to categorize venous mesenteric variants and to determine their incidence. MATERIALS AND METHODS: We included 916 patients requiring diagnostic abdominal CT in the portal venous phase. The mesenteric vein anatomy was categorized as follows: 1. the inferior mesenteric vein (IMV) enters the splenic vein (SV); 2. the IMV enters into the angle of the confluence of the SV and superior mesenteric vein (SMV) forming the portal vein (PV); 3. the IMV enters the SMV; 4. seven rare variants. We measured the diameters of the veins and distances from the confluence to the IMV origins. RESULTS: The frequency of variants was: 1. 37.6%, 2. 28.8%; 3. 19.2%. The rare variants totaled 14.4%. The average vessel diameters measured in cm: PV 1.48; SV 1.02; SMV 1.2; IMV 0.5. The mean IMV entering distances were 1.66 cm in variant 1 and 0.75 cm in variant 3. CONCLUSION: The three common variants (1, 2 and 3) are the most relevant ones. 14.4% of patients had different anatomic variants. The variability of the mesenteric venous system was higher than previously published. Knowledge of rare variants is important to avoid complications in abdominal surgery.

[Vascular replacement in abdominal tumor surgery]. / Gefässersatz in der abdominellen Tumorchirurgie.

As part of oncologic visceral surgical operations the surgeon is confronted with anatomical barriers. In particular abdominal sarcomas and carcinomas sometimes require a vascular surgical procedure in order to achieve a radical and curative treatment. By using vascular surgical techniques there is the possibility for oncology patients to expand the boundaries of operability and to allow a long tumor-free survival. For each affected arterial and venous structure there are special reconstruction methods which require an optimal vascular graft. The aim of vascular resection and reconstruction should focus not only on the radicality of the operation but should also take the optimal circulation recovery of blood in the tumor resected area into account.

Vascular encasement as element of risk stratification in abdominal neuroblastoma.

BACKGROUND: Vascular encasement of major vessels has been introduced as element of image defined risk factors (IDRF) for stratification of abdominal neuroblastoma. Some subgroups of this tumor entity are still subject of discussion regarding surgical approach and radicality. Aim of this study was to analyse a cohort of related patients. PATIENTS AND METHODS: Children operated on for neuroblastoma with encasement of major abdominal vessels (April 2002-April 2009) were retrospectively evaluated regarding surgical procedures, intra- and postoperative complications, and outcome. RESULTS: There were 18 patients with abdominal NB and encasement of major vessels. Mean age at operation was 43.5 months (2.5-113), mean operation time was 228 minutes (157-428). Complete macroscopic tumor resection was realised in 14 children. Vascular reconstruction was necessary in 5 patients. Tumor progression/relapses requiring further operation occurred in 3 patients. Major postoperative complications were 1 loss of unilateral renal function with subsequent nephrectomy, 1 renal vein thrombosis (operative revision), 1 renal artery embolism (operative revision), and 1 ureteral obstruction (stenting). Mean follow up was 34.8 months (2-78). CONCLUSIONS: Vascular encasement as part of IDRF is a valuable tool for stratification of abdominal NB. Surgery of NB with vascular encasement includes divers and complex procedures. Children seem to benefit from complete tumor resection or at least relevant tumor reduction although operations can mean a relevant strain for the patients.

Characterization of intra-abdominal lesions of undetermined origin by contrast-enhanced harmonic EUS (with videos).

BACKGROUND: The diagnosis of intra-abdominal lesions of undetermined origin is often a challenge for endoscopists and radiologists. OBJECTIVE: To evaluate the microvasculature of benign and malignant intra-abdominal lesions by contrast-enhanced harmonic EUS (CEH-EUS) and to investigate its usefulness for discriminating between malignant and benign lesions. DESIGN: The vascularity of intra-abdominal lesions of undetermined origin was observed by using CEH-EUS. The lesions were classified according to their vascular patterns. The effectiveness of CEH-EUS in differentiating malignant from benign lesions was evaluated. SETTING: Kinki University School of Medicine, Osaka, Japan. PATIENTS: Forty-three patients, each with a lesion of undetermined origin, were evaluated prospectively by CEH-EUS between March 2007 and March 2009. INTERVENTIONS: CEH-EUS was performed by using a prototype echoendoscope and the extended pure harmonic detection mode (a specific mode for contrast harmonic imaging). MAIN OUTCOME MEASUREMENTS: The lesions were categorized by 2 physicians as having no, homogeneous, or heterogeneous enhancement. A consensus was reached for each case offline. How the benign and malignant groups differed in terms of their enhancement patterns was examined. RESULTS: The kappa coefficient of the interobserver agreement test was 0.953 (P < .001). Of the 27 malignant lesions, 26 (96.3%) exhibited heterogeneous enhancement. The 1 remaining malignant lesion (3.7%) showed homogeneous enhancement. Of the 16 benign lesions, none displayed heterogeneous enhancement, and 12 (75%) and 4 (25%) exhibited homogeneous and no enhancement, respectively. The malignant and benign lesion groups differed significantly in terms of homogeneous and heterogeneous enhancement (P < .001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy with which CEH-EUS differentiated malignant from benign lesions were 96.3%, 100%, 100%, 94.1%, and 97.6%, respectively. LIMITATIONS: A single medical unit with a limited number of patients. CONCLUSIONS: CEH-EUS depicted the microvasculature of intra-abdominal lesions of undetermined origin very clearly and may be useful for characterizing such lesions.

Large paraganglioma of the abdominal cavity: a case report and review of the literature.

BACKGROUND: Paragangliomas are rare tumors that derive from cells of the autonomic nervous system. They are usually located in the neck, i.e. arising from the glomus caroticum or glomus jugulare, but may also be located in the mediastinum and abdominal cavity arising from other ganglia. Paraganglioma located in the adrenal gland are called pheochromocytoma. CASE REPORT: We report a case of an oligosymptomatic 50-year-old man presenting with a large intraabdominal tumor mass measuring 24 x 22 x 12 cm. Core needle biopsy revealed a tumor of mesenchymal origin with no clear-line differentiation, so the highly vascularized tumor was resected after embolization of the tumor vessels. Histology revealed epithelioid cells with expression of CD68 and CD10 but no expression of Pan-CK, CD30, or CD45. Ki67 staining was 20%. Lymphangiosis and angioinvasion were demonstrated. Differential diagnosis included histiocytic sarcoma and c-kit-negative gastrointestinal stromal tumor; the final diagnosis was paraganglioma. The 6-month follow-up showed no evidence of recurrence. CONCLUSIONS: Paraganglioma is a rare disease and should be considered in the differential diagnosis of abdominal masses. To our knowledge, this report is of the largest paraganglioma that has been described in the literature so far. Nomenclature, pathogenesis, and treatment options are discussed.

[Differentiation of abdominal lymphadenoptahy with power Doppler sonography]. / Dignitätsbeurteilung von abdominellen Lymphadenopathien in der Powerdoppler-Sonografie.

PURPOSE: Recent studies have reported high accuracy of power Doppler sonography (PDS) and color Doppler sonography (CDS) in the differentiation of benign and malignant peripheral superficial lymphadenopathy. This study was conducted to determine whether PDS can differentiate benign from malignant abdominal lymph nodes on the basis of defined vascular patterns. MATERIALS AND METHODS: We retrospectively evaluated 88 color pictures of abdominal lymph nodes (39 benign lymph nodes, 24 malignant lymphomas, 25 lymph node metastasis) done in the power Doppler mode. The goal was to determine whether benign and malignant abdominal lymph nodes can be differentiated in power Doppler sonography on the basis of 9 defined vascular patterns. RESULTS: Three vascular patterns showed a significantly (p < 0.05) higher appearance in malignant than in benign lymph nodes: aberrant vessel (specificity 87 %), avascular focus (specificity 92 %) and subcapsular vessel (specificity 100 %). The vascular pattern hiliar vessel showed a significantly higher appearance in benign lymph nodes (specificity 87.8 %). CONCLUSION: Three vascular patterns are detectable in power Doppler mode (avascular focus, aberrant vessel, subcapsular vessel) in abdominal lymph nodes, which are typical for malignant abdominal lymphadenopathy. The presence of one of these vascular patterns means with a high specificity (87 - 100 %) that an abdominal lymphadenopathy is malignant. One vascular pattern (hiliar vessel) shows a significantly higher appearance in benign lymph nodes.