Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia.

Background: Cachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit. Methods: Serum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis. Results: Comparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways. Conclusion: We found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.

High In-Hospital Mortality in SARS-CoV-2-Infected Patients with Active Cancer Disease during Omicron Phase of the Pandemic: Insights from the CORONA Germany Study.

INTRODUCTION: SARS-CoV-2 infected patients with cancer have a worse outcome including a significant higher mortality, compared to non-cancer patients. However, limited data are available regarding in-hospital mortality during the Omicron phase of the pandemic. Therefore, the aim of the study was the comparison of mortality in patients with history of cancer and patients with active cancer disease during the different phases of the COVID-19 pandemic, focusing on the current Omicron variant of concern. METHODS: We conducted a multicenter, observational, epidemiological cohort study at 45 hospitals in Germany. Until July 20, 2022, all adult hospitalized SARS-CoV-2 positive patients were included. The primary endpoint was in-hospital mortality regarding cancer status (history of cancer and active cancer disease) and SARS-CoV-2 virus type. RESULTS: From March 11, 2020, to July 20, 2022, a total of 27,490 adult SARS-CoV-2 positive patients were included in the study. 2,578 patients (9.4%) had diagnosis of cancer, of whom 1,065 (41.3%) had history of cancer, whereas 1,513 (58.7%) had active cancer disease. Overall 3,749 out of the total of 27,490 patients (13.6%) died during the hospital stay. Patients with active cancer disease had a significantly higher mortality compared to patients without cancer diagnosis, in both phases of the pandemic (wild-type to Delta: OR 1.940 [1.646-2.285]); Omicron: 2.864 [2.354-3.486]). After adjustment to co-variables, SARS-CoV-2 infected patients with active cancer disease had the highest risk for in-hospital mortality compared to the other groups, in both phases of the pandemic. CONCLUSION: The CORONA Germany study indicates that hospitalized patients with active cancer disease are at high risk of death during a SARS-CoV-2 infection. Mortality of patients with history of cancer improved to nearly the level of non-cancer patients during Omicron phase.

Potential for cure and predictors of long-term survival after radiofrequency ablation for colorectal liver metastases: A 20-years single-center experience.

BACKGROUND: Additional radiofrequency ablation (RFA) of liver-limited colorectal liver metastases (CRLM) improves overall (OS) and recurrence-free survival (RFS) over systemic therapy alone. We aimed to assess the potential and predictive factors of long-term survival and cure to optimize patient selection for RFA application. METHODS: Retrospective review of a prospectively maintained single-center database of consecutive patients undergoing RFA for liver-limited CRLM after systemic therapy between 2002 and 2020. Clinicopathologic characteristics and KRAS/BRAF-genotype data (tested routinely since 2010) were correlated to RFS and OS. Cure was defined as ≥10-years RFS (long-term survival as ≥5-years OS) following RFA. RESULTS: For the entire cohort of 158 patients (median follow-up 13.6 years), co-occurrence of three factors, RECIST-defined response, number of ≤3 CRLM, and ≤3 cm maximum size determined a survival plateau that distinguished cured from non-cured patients (10-years RFS: 15.5% vs 0%, p < 0.0001). Among 59 patients (37.3%) being tested, 4(6.8%) were BRAF-mt, 15(25.4%) KRAS-mt, and 40(67.8%) KRAS/BRAF-wt. OS (median follow-up 8.3 years) was estimated to be higher with KRAS/BRAF-wt compared to a mutant KRAS or BRAF status (5-years OS: 22.8% vs 3.4%, p = 0.0018). CONCLUSION: This study indicates about 15% chance of cure following RFA of low-volume liver-limited CRLM after downsizing by systemic therapy and a negative effect of KRAS or BRAF mutation on long-term survival after CRLM ablation. These findings may improve clinical decision-making in patients potentially candidate to RFA of CRLM and encourage further investigations on molecular factors determining an oligometastatic state of CRLM curable with focal ablative therapy.

MicroRNAs in blood act as biomarkers of colorectal cancer and indicate potential therapeutic targets.

Association studies have linked alterations of blood-derived microRNAs (miRNAs) with colorectal cancer (CRC). Here, we performed a microarray-based comparison of the profiles of 2549 miRNAs in 80 blood samples from healthy donors and patients with colorectal adenomas, colorectal diverticulitis and CRC at different stages. Confirmation by quantitative real-time PCR (RT-PCR) was complemented by validation of identified molecules in another 36 blood samples. No variations in miRNA levels were observed in samples from patients with colorectal adenomas and diverticulitis or from healthy donors. However, there were 179 CRC-associated miRNAs of differential abundance compared to healthy controls. Only three - miR-1225-5p, miR-1207-5p and miR-4459 - exhibited increased levels at all CRC stages. Most deregulated miRNAs (128/179, 71%) specifically predicted metastatic CRC. Pathway analysis found several cancer-related pathways to which the miRNAs contribute in various ways. In conclusion, miRNA levels in blood vary throughout CRC progression and affect cellular functions relevant to haematogenous CRC progression and dissemination. The identified biomarker and therapeutic candidates require further confirmation of their clinical relevance.

Intraoperative (Contrast-Enhanced) Ultrasound Has the Highest Diagnostic Accuracy of Any Imaging Modality in Resection of Colorectal Liver Metastases.

AIM: Defining sensitivity, specificity, diagnostic accuracy for detection of colorectal liver metastases in imaging compared to intraoperative assessment. Defining a cutoff, where accuracy of detection is impaired. METHODS: Prospective single-institution clinical trial (clinicaltrials.gov: NCT01522209). Patients underwent CEUS, MDCT, and 3 Tesla EOB-MRI within 2 weeks preoperatively. Intraoperative palpation, IOUS, and CEIOUS were performed. A patient and lesion-based database was analyzed for accuracy of detection of CEUS, CT, MRI, and Palp/IOUS/CEIOUS combined read. Histology was standard of reference. RESULTS: Forty-seven high tumor load (mean 5, 4 lesions) patients were analyzed. Histopathology confirmed 264 lesions (245 malignant: 19 benign). Accuracy for detection of all lesions: CEUS 63%, CT 71%, MRI 92%, and PALP/IOUS/CEIOUS 98%. ROC analysis for lesion size showed severe impairment of accuracy in lesion detection smaller than 5mm. Intraoperative imaging was not impaired by lesion size. Patient-based analysis revealed a change of resection plan after IOUS/CEIOUS in 35% of patients. CONCLUSION: At 5-mm lesion size, preoperative imaging shows a drop in accuracy of detection. In patients with multiple lesions, addition of MRI to MDCT seems useful. Accuracy of intraoperative ultrasound is not impacted by lesion size and should be mandatory. CEIOUS can improve intraoperative decision-making. TRIAL REGISTRATION: Study registered with clinicaltrials.gov : NCT01522209.

[Diagnostic and prognostic significance of α-fetoprotein in hepatocellular carcinoma]. / Diagnostische und prognostische Bedeutung des α-Feto-Proteins beim hepatozellulären Karzinom.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive tumor with a growing socioeconomic burden. International guidelines do not predominantly recommend the pretherapeutic determination of the alpha-fetoprotein (AFP) concentration. Regarding the prognostic value of AFP, the European study data are not sufficiently meaningful. OBJECTIVE: This study aimed to demonstrate possible aspects of the AFP level and to investigate the prognostic value of AFP levels as well as to provide impetus for future prospective studies. MATERIAL AND METHODS: At the time of data retrieval the prospective liver databank showed 1382 entries. All patients with a histologically confirmed HCC were included resulting in 92 final entries. For these patients, information on T, N, M and G stages, R status as well as sex, age and etiology of the HCC were available. For data analysis the patient population was divided into six groups based on three cut-off values. Furthermore, a survival analysis was performed using Kaplan-Meier and a multifactorial analysis of the influencing factors regarding outcome. RESULTS: The AFP serum level showed a statistically significant correlation with the tumor diameter (T1/T2 vs. T3/T4) and grading (G1/G2 vs. G3/G4). The survival prognosis was significantly lower in patients with higher AFP values (p < 0.05). The median survival time for patients with AFP levels >8 µg/l was 35 months, with AFP levels >200 µg/l or >400 µg/l showed a reduced median survival of 15 months and 11 months, respectively. High AFP levels were a significant influencing factor for the outcome independent of the T stage, age and R status of patients in comparison to low AFP levels. CONCLUSION: Taking the present results into consideration, the AFP level can have a therapeutic usefulness. Therapeutic consequences could be derived from the height of the measured AFP concentration, with respect to the treatment strategy. Therefore, preoperative and postoperative determination of the AFP serum level is recommended in all HCC patients.

Extending resectability of hilar cholangiocarcinomas: how can it be assessed and improved?

Until the 1980's, Klatskin tumors were considered 'desperate cases' and most of them were not resected; almost no oncologic concept was available. After many improvements, today, extended hepatectomy, including caudate lobe resection and lymphoadenectomy, have become a standard of care for oncologicaly radical resection of Klatskin tumors. Portal vein en bloc resection, if necessary, is a diffused standard assuring R0-resection without any improvement of survival in most series. Arterial resection remains episodical and controversial in its oncologic impact. Arterial resection-reconstruction was demonstrated to be feasible with many different technical possibilities. Neoadjuvant chemotherapy, refinement of associating liver partition and portal vein ligation for staged hepatectomy and liver transplantations are some possible future resources for treatment of those aggressive tumors that could be able to expand the pool of treatable patients.

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.

Did the International ALPPS Meeting 2015 Have an Impact on Daily Practice? The Hamburg Barmbek Experience of 58 Cases.

BACKGROUND: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was introduced only 10 years ago and has gained wide acceptance as a variation of staged procedures in liver surgery. It has been criticized for its high morbidity and mortality, which all centers reported in their initial series. METHODS: After a world expert meeting in Hamburg in 2015 where all experts in the field met to discuss this method, caveats were extracted and formulated. We researched our complete prospective ALPPS database to see if the recommendations had any impact on outcome. RESULTS: In total, we performed 58 ALPPS procedures in our center. 33 patients were operated on before, 25 after the meeting. Results in terms of morbidity and mortality were significantly better after the meeting, as were patient selection and strategy. CONCLUSION: In our own center's experience, the implementation of the meetings' recommendations and the information gathered through this valuable exchange had a dramatic impact on results. Having performed 58 ALPPS procedures in total, we can now conclude that ALPPS has become much safer in our hands since the 2015 meeting and that morbidity and mortality are no longer the issue to be discussed. Future research must focus on oncologic outcomes in these patients.

Impact of Systemic Therapy and Recurrence Pattern on Survival Outcome after Radiofrequency Ablation for Colorectal Liver Metastases.

Background: Most patients undergoing radiofrequency ablation (RFA) of colorectal liver metastasases (CLM) develop disease recurrence, but little is known about the effect of recurrence patterns and/or systemic therapy on outcome. In this study, we examined the recurrence patterns and survival after systemic therapy plus RFA in patients with unresectable CLM without extrahepatic disease. The aims were to analyze the effect of recurrence patterns on survival and to assess the relative benefit contributed by systemic therapy and local ablation to disease control and patient outcome. Methods: From January 2002 to December 2012, 113 patients underwent RFA of liver-limited CLM after systemic therapy. Univariate and multivariate analyses for associations between clinical and/or treatment-related variables, recurrence-free survival (RFS), recurrence patterns, and overall survival (OS) were carried out. Results: Of 113 patients, 105 (92.8%) had disease recurrence (median RFS: 6.1 months). Lower post-recurrence OS was observed after early (≤6 months) than after late recurrence (8.5 versus 24.0 months, p < 0.001). Recurrence sites were RFA-sites only (4.8%), liver-only (57.1%), lung-only (10.5%), or multiple (27.6%); the corresponding post-recurrence OS was 21, 19, 39, and 7 months (p < 0.001), respectively. Response to pre-RFA systemic therapy was the strongest predictor for OS (hazard ratio [HR] 5.28), RFS (HR 3.30), early (odds ratio [OR] 6.34) and multiple-site recurrence (OR 3.83) (p < 0.01), respectively; only responders achieved 5-year OS and RFS (29% and 12% versus 0% and 0% for non-responders, p < 0.001, respectively). Conclusions: Survival after RFA for liver-limited CLM is strongly linked to the timing and pattern of non-local disease recurrence. Local ablation efficacy is necessary but not sufficient to obtain long-term disease control. Effective pre-RFA systemic therapy does favourably affect the incidence, timing and patterns of recurrence and long-term survival and appears essential for the tailoring of RFA application to maximize patient benefit.

Identification of cofactors influencing hypertrophy of the future liver remnant after portal vein embolization-the effect of collaterals on embolized liver volume.

OBJECTIVE: The purpose of this retrospective study was to monitor hypertrophy of future liver remnant following portal vein embolization (PVE) before planned extended right hepatectomy. However, because individual responses to PVE are highly variable, our focus was to identify cofactors of successful hypertrophy. METHODS: 28 patients with primary or secondary liver tumours, mean age 64.1 ± 12.9 years, underwent PVE. Volumetric analysis of hypertrophy before and after PVE (median 39.0 ± 15.7 days) was performed. The embolized liver segments were investigated for occurrence of reperfusion of their portal branches. Blood parameters before PVE were additionally investigated. RESULTS: Patients were divided into responders (21/28) and non-responders (7/28) by post-PVE standardized future liver remnant being above or below 25%, respectively. No significant differences between the groups were found regarding biometric and volumetric parameters before PVE. In the entire group after PVE, the mean absolute increase of Segments 2 and 3 was 196.0 ± 84.7 cm3 and the median relative increase was 46.6 ± 98.8%. The formation of left to right hepatic portoportal collaterals exhibited a negative correlation to successful hypertrophy (p = 0.004) as well as low plasma total protein (p = 0.019). Successful embolization of Segment IV showed only a trend to significance (p = 0.098). CONCLUSION: Cofactors associated with a favourable outcome regarding hypertrophy were the absence of collaterals in the control CT scans and high plasma total protein. Advances in knowledge: Portoportal collaterals negatively influence hypertrophy after PVE. On the other hand, plasma total protein is a positive prognostic indicator on hypertrophy of the liver in our cohort.

'Liver-first' approach for metastatic colorectal cancer.

The liver-first approach was proposed for the first time in 2006 to obtain resectability of stage IV colorectal cancer patients and complete the therapeutic plan. From then some groups have used this new revolutionary approach reporting promising results. Other alternative strategies have been proposed for metastatic patients. The authors reviewed the literature weighing the pros and cons of each strategy proposed to manage these advanced tumor stages. The therapeutic options are analyzed in the light of oncologic problems and evidence. Also problems, questions and perspectives are given. Even if the 'liver-first' approach seems to be a promising strategy, the ideal diagnostic-therapeutic flowchart for metastatic colorectal cancer is still difficult to standardize. The great heterogeneity of this population of patients is one of the main problems. A 'tailored approach' philosophy is necessary to calibrate, in a multidisciplinary setting, a case-by-case choice of therapeutic options.

Selection criteria for radiofrequency ablation for colorectal liver metastases in the era of effective systemic therapy: a clinical score based proposal.

BACKGROUND: At present, there are no widely accepted criteria for the use of radiofrequency ablation (RFA) for the treatment of colorectal liver metastases (CLM) in the context of effective modern-agent therapies. We aimed to define selection criteria for patients with liver-limited CLM who may benefit from adding RFA to systemic therapy with respect to long-term disease control. METHODS: Between 2002 and 2007, 88 consecutive patients received RFA for liver-only CLM during partial remission (PR), stable disease (SD), or progressive disease (PD) after systemic therapy. At a median follow-up of 8.2 years (range 5.2-11.1 years), clinical data were correlated to overall survival (OS) and recurrence-free survival (RFS). RESULTS: Poor OS and RFS correlated significantly with PD to systemic therapy before RFA (HR 5.46; p < 0.0001; and HR 6.46; p < 0.0001), number of ≥4 CLM (HR 3.13; p = 0.0005; and HR 1.77; p = 0.0389), and carcinoembryonic antigen (CEA) level of ≥100 ng/ml (HR 1.67; p = 0.032; and HR 1.67; p = 0.044). The presence of four criteria (PR, ≤3 CLM, ≤3 cm maximum size, and CEA ≤100 ng/ml) selected a subgroup (n = 23) with significantly higher probabilities for OS and RFS at 5 years (39% and 22%,respectively) compared to those without any or up 3 of these criteria (0-27% and 0-9%, p < 0.001, respectively). CONCLUSIONS: A score based on four criteria (response to systemic therapy, ≤3 CLM, ≤3 cm size, low CEA value) may allow to select patients with liver-only CLM for whom additional use of RFA most likely adds benefit in an attempt to achieve long-term disease control. Almost one-fourth of patients fulfilling these four criteria may achieve 5-year survival without disease recurrence following effective systemic plus local RFA treatment.

ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a promising method to increase resectability rates of liver tumors. Little has been published about oncological results so far. This report describes clinical evidence regarding a possible effect of ALPPS on tumor recurrence. METHODS: Ten ALPPS procedures were performed for otherwise non-resectable colorectal liver metastases. Seven of these ten patients had a follow-up of at least 3 months and were analyzed for tumor recurrence. RESULTS: Six of these seven patients had tumor recurrence to the liver. Three of seven patients presented with lung metastases, occurring earlier than liver metastases in two of three cases. One patient with a follow-up of 3 months had no visible recurrent disease, but increasing carcinoembryonic antigen levels. CONCLUSIONS: The patient group operable only through ALPPS is at high risk for recurrence and early tumor progression. Still, this new method is the only chance for an oncological treatment strategy including a surgical approach and possibly better outcome.

Staging colorectal cancer with the TNM 7(th): the presumption of innocence when applying the M category.

One of the main changes of the current TNM-7 is the elimination of the category MX, since it has been a source of ambiguity and misinterpretation, especially by pathologists. Therefore the ultimate staging would be better performed by the patient's clinician who can classify the disease M0 (no distant metastasis) or M1 (presence of distant metastasis), having access to the completeness of data resulting from clinical examination, imaging workup and pathology report. However this important change doesn't take into account the diagnostic value and the challenge of small indeterminate visceral lesions encountered, in particular, during radiological staging of patients with colorectal cancer. In this article the diagnosis of these lesions with multiple imaging modalities, their frequency, significance and relevance to staging and disease management are described in a multidisciplinary way. In particular the interplay between clinical, radiological and pathological staging, which are usually conducted independently, is discussed. The integrated approach shows that there are both advantages and disadvantages to abandoning the MX category. To avoid ambiguity arising both by applying and interpreting MX category for stage assigning, its abandoning seems reasonable. The recognition of the importance of small lesion characterization raises the need for applying a separate category; therefore a proposal for their categorization is put forward. By using the proposed categorization the lack of consideration for indeterminate visceral lesions with the current staging system will be overcome, also optimizing tailored follow-up.

A compartment-specific transcriptome analysis reveals survival-relevant marker genes in the stroma fraction of squamous non-small cell lung cancer.

Although it is increasingly recognized that the tumor biology is influenced by the tumor stroma, prognostic gene signatures are usually derived from tissue consisting of tumor cells and surrounding stroma. This study presents a compartment-specific transcriptome analysis of lung squamous cell carcinoma (SCC) samples microdissected into tumor parenchyma and stroma fractions. Typical tumor and stroma genes were identified based on the expression ratios between the two compartments. Our results indicate that in SCC many markers related to longer survival are predominantly expressed in the stroma, particularly genes of the MHC-II complex. Stromal upregulation of MHC-II genes seems crucial for a clinically relevant antitumor immune response in SCC.

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 < or = 1 cm) hepatic lesions in 25 patients, including 65 (25 < or = 1 cm) metastases in 16 patients (M1). Regarding the 45 < or = 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.

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.