Prognostic relevance of serial endoscopic ultrasound after chemoradiation in esophageal cancer.

The objective of this study is the feasibility of sequential endoscopic and endosonographic measurement of locoregional tumor load for the prediction of tumor recurrence in patients after neoadjuvant or definitive chemoradiotherapy, treated in curative intent for locally advanced esophageal carcinoma. In 67 patients with esophageal cancer, serial endoscopic ultrasound was performed before and after neoadjuvant (25) or definitive (42) chemoradiotherapy. Rate of complete endoscopic and endosonographic tumor response, reduction in tumor length or circumferential tumorous extension, maximal tumor thickness, lymph node size, and endosonographic uT- and uN-stage shift was measured. Results were correlated with tumor recurrence rate. After chemoradiotherapy, endosonography revealed a complete response of the primary tumor in 27 patients, and complete resolution of suspicious lymph nodes in 24 patients. According to uTN-stage, 43 patients showed a therapeutic response, with stage shift to a lower tumor stage. In patients with macroscopic residual disease, mean tumor thickness decreased from 13 to 9 mm, with nine patients presenting with a decrease of >50%. Mean tumor length decreased from 5.6 to 4.6 cm, with 10 patients showing a decrease of >50%. Mean lymph node size decreased from 14.5 to 12 mm, with four patients having a reduction in size of >50%. Tumor response was generally more pronounced after definitive than after neoadjuvant chemoradiotherapy. During follow-up, 33 patients developed a tumor recurrence. None of the endoscopic and endosonographic parameter analyzed was predictive for patient's prognosis, irrespective of the kind of chemoradiotherapy (neoadjuvant or definitive). Sequential measurement of locoregional tumor load with endoscopic ultrasound before and after chemoradiotherapy is not suitable for the prediction of tumor recurrence risk.

Improvement in advanced pancreatic cancer survival with novel chemotherapeutic strategies - experience of a community based hospital.

Background: New chemotherapeutic strategies for locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) have been shown to improve survival in randomized clinical trials. Little is known about the use of such chemotherapies and their benefit in community-based hospitals. This retrospective study analyzes the overall survival of these patients under "real life conditions" before and after the introduction of FOLFIRINOX in 2011. Methods: We retrospectively identified consecutive patients with PDAC who were treated at our hospital from 2011 to June 2014 (2011+ cohort) and 2004 to 2010 (historical cohort). Patients were included if PDAC was diagnosed in a locally advanced or metastatic state and at least 1 cycle of chemotherapy was given. Survival was assessed until April 2016. Patients with FOLFIRINOX were further analyzed regarding drug administration and side effects. Results: 128 patients met the inclusion criteria. Of the 74 patients in the historical cohort, 62 patients received Gemcitabine. Of the 54 patients diagnosed between 2011 and June 2014, 28 patients received FOLFIRINOX and 22 Gemcitabine as the first-line chemotherapy. Only 34 % of the patients in the historical cohort received a second-line chemotherapy in comparison to 69 % in the 2011+ cohort. Median overall survival (OS) showed a survival of 13.1 months (95 % CI; 11.6 - 14.5) for the 2011+ cohort compared to 9.6 months (95 % CI; 6.1 - 13.1) in the historical group. Conclusion: This study shows a marked improvement in survival of patients diagnosed with locally advanced or metastatic PDAC in a community-based hospital during the past 4 years. The most likely reasons are the use of new polychemotherapies like FOLFIRINOX and the use of second-line chemotherapy.

Ultrasound in radioembolization induced liver disease (REILD).

BACKGROUND: REILD (radioembolization-induced liver disease) is a rare complication after SIRT (selective internal radiotherapy) of the liver. The diagnosis is based on a combination of clinical signs and symptoms, laboratory values, and MRT findings. Data about sonographic signs associated with REILD are lacking. In this report, we describe sonographic changes in two female patients with REILD. CASE REPORTS: Patient 1: a 34-year-old woman with colorectal carcinoma liver metastasis. Two weeks after SIRT, the patient developed histology-proven REILD. Abdominal ultrasound revealed pronounced hepatomegaly, with inhomogeneous, slightly hyperechoic parenchyma without attenuation. The well-known metastasis could not be delineated easily. Liver veins were compressed, with ill defined borders, and flattened biphasic blood flow in duplex sonography. Signs of portal hypertension with ascites, and splenomegaly were present. A therapy with diuretics, heparin, steroids, and ursodesoxycholic acid was introduced, and the patient recovered. After seven weeks, the ascites had resolved, and the liver parenchyma returned to normal echogenicity. Furthermore, the metastases in both lobes were clearly visible again. The liver veins were well delineated, normal sized, with regular triphasic blood flow in duplex sonography, but splenomegaly persisted. Patient 2: a 58-year-old women with recurrent multifocal peripheral cholangiocarcioma. Abdominal ultrasound 5 weeks after SIRT revealed a slightly increased echogenicity of the liver. Liver veins showed slightly irregular borders with biphasic flow pattern. In contrast to patient no.1, liver metastases could still be delineated easily. Ascites or splenomegaly were not present. Laboratory parameters and MRT findings were consistent with a diagnosis of mild REILD. Liver biopsy was not performed. No specific therapy was introduced. Five weeks later, the liver parenchyma became more homogeneous again, and the liver veins normalized with smooth vessel borders, but still flattened biphasic flow pattern. CONCLUSION: Transient hepatomegaly, with inhomogeneous hyperechoic parenchyma without attenuation, and compressed, ill delineated liver veins, with monophasic or flattened biphasic blood flow, are typical sonographic findings in REILD. In addition, common signs of portal hypertension can be present. Liver alterations and ascites resolve parallel with clinical improvement. Splenomegaly can persist.

Mediastinitis after EUS-FNA in a patient with sarcoidosis - case report with endosonographic features and review of the literature.

BACKGROUND: EUS-FNA of lymph nodes is believed to harbour no risk of serious complications. However, recently, a case series of mediastinal abscess formation after EUS-FNA in patients with sarcoidosis has been published. Here, we describe a patient with sarcoidosis and mediastinitis after EUS-FNA. CASE REPORT: Two years before EUS-FNA, the patient with a history of sarcoidosis, was operated because of esophageal adenocarcinoma. Due to progredient mediastinal lymphoma, we performed EUS-FNA to exclude tumor recurrence. 30 hours later, the patient developed general weakness, musculoskeletal pain, non-productive cough, and mild dysphagia. Ten days later, the patient was admitted with fever and thrombocytopenia. A CT scan showed a mediastinal mass without liquid areas, but small deposits of air. Meropenem, steroid, and low-dose heparin were started. The fever resolved after 24 hours, CRP, as well as coagulatory parameters returned to normal levels after 5 days. Endoscopic ultrasound revealed an inhomogeneous, slightly hyperechoic, mediastinal mass. The lymph nodes were partly dislodged, and partly embedded into this mass with a rounded shape and large hyperechoic center. Vascularization was not increased, liquid areas, or inclusions of gas were not present. A follow-up examination 6 weeks later revealed complete resolution of the mass. CONCLUSION: EUS-FNA, but not EBUS-FNA, seems to be associated with an increased infectious risk in patients with sarcoidosis. Endosonographic features include inhomogeneous, mass-forming mediastinal infiltration, and swelling of lymph nodes with hyperechoic central parts. In cases of suspected sarcoidosis, EBUS-FNA should be preferred. EUS-FNA, probably with antibiotic prophylaxis, should only be done after a non-diagnostic bronchoscopic work-up.

[Validity of endoscopic ultrasonography-guided fine needle aspiration of mediastinal and abdominal lymph nodes in daily clinical practice]. / Endosonographisch gesteuerte Feinnadelpunktion bei mediastinalen und abdominellen Lymphknotenvergrößerungen.

BACKGROUND: According to recent clinical trials, EUS-FNA has a high diagnostic yield in case of mediastinal and abdominal lymphadenopathy. However, it is questionable, if the results of centers of excellence can be maintained in daily clinical practice. METHODS: We retrospectively analyzed the results of 141 EUS-FNP in 121 patients (female 25, male 86; mean age 61,5 years, range 22-87) of 119 mediastinal and 22 abdominal lymph nodes, performed under routine conditions in daily clinical practice in a community hospital. Histopathological examination of operative specimens or clinical follow-up served as gold standard. RESULTS: In 124/141 (80 %) of cases, adequate specimens could be obtained, irrespective of lymph node size. During follow-up, the rate of adequate specimens obtained increased from 77 % (2002-2006) to 98 % (2007-2010). Sensitivity and specifity for the diagnosis of malignancy was 77 and 100 % (diagnostic accuracy 92 %). During follow-up, a relevant learning curve could be observed with a significant increase in sensitivity (72 to 80 %). CONCLUSION: In comparison to the results of centers of excellence, our diagnostic accuracy is slightly inferior. However, even in daily routine praxis, EUS-FNP is a safe and accurate method of sampling mediastinal and abdominal lymph nodes.

[The change of pathology in the era of personalized medicine using the example of discordant KRAS mutational status in metastasized colorectal carcinoma]. / Der Wandel der Pathologie in der Ära der personalisierten Medizin. Eine Übersicht am Beispiel des diskordanten KRAS-Mutationsstatusbeim metastasierten kolorektalen Karzinom.

Modern pathology has developed from "omega" to "alpha" and is vital for therapy and follow-up of tumor treatment today. Pathology has a key role as part of personalized medicine. It is possible to intervene therapeutically into the molecular genetic intricacy of tumors by establishing predictive biomarkers with corresponding tumor therapeutic agents.By identifying the KRAS mutational status at the metastasized colorectal carcinoma, a statement about the benefit of an anti-EGFR-therapy can be given, which is nowadays the basis of diagnostic and therapy of this cancer.For a long period of time a high concordance between primary and metastases inside the KRAS status was taken for granted. Meanwhile, there are many studies demonstrating a possibly underestimated high degree of discordance. The identification of discordances might gather a subcollective, which partially holds a KRAS wild type tissue and thereby might respond with a partial remission. Thus, the survival time of these patients and their quality of living could be successfully improved.

Contrast-enhanced ultrasound (CEUS) for differentiating between hepatocellular and cholangiocellular carcinoma.

PURPOSE: HCC and CC are the most common primary malignancies of the liver. There is only minimal evidence as to whether these two entities can be reliably differentiated by contrast-enhanced ultrasound. MATERIALS AND METHODS: We retrospectively analyzed the CEUS pattern of 39 patients with HCC, 11 patients with intrahepatic cholangiocarcinoma (ICC), 3 patients with Klatskin tumor, and 4 patients with gallbladder carcinoma. CEUS was performed using a standardized protocol (low MI, SonoVue®) with documentation of the arterial, portal-venous, and late phase. Besides the contrast enhancement compared to the adjacent normal liver tissue in every phase, the specific contrast pattern during the arterial phase (complete filling, incomplete filling of different grade, rim sign) was analyzed. RESULTS: Most HCC and ICC showed hyperenhancement during the arterial phase, with hypoenhancement or isoenhancement in the portal-venous and late phase. Hyperenhancement during the portal-venous phase was only observed in some cases of HCC, but not in ICC. In the case of arterial hyperenhancement, HCC showed complete filling more often than ICC. In the case of incomplete filling, the area of contrast-enhanced tumor in most HCCs was larger than in ICCs. A rim sign was present in only less than half ICCs, but in no HCCs. CONCLUSION: HCC and ICC differ to some extent in their CEUS enhancement pattern. Incomplete arterial hyperenhancement is more often seen in ICC than in HCC. A rim sign seems to be specific for ICC, but is only rarely present. However, in a case-to-case decision, due to overlapping characteristics, a reliable differentiation between the two tumor types by CEUS alone is very often not possible.

High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers.

OBJECTIVE: High-dose vitamin C therapy might mediate beneficial clinical effects by counteracting reactive oxygen species. However, concerns are raised whether this approach might provoke diametrical (ie pro-oxidative) effects. The objective was to determine ascorbyl free radical (AFR) concentrations and potential variables of pro-oxidative damage. DESIGN: Crossover study; six healthy males received daily infusions of 750 or 7500 mg vitamin C for six consecutive days. Fasting concentrations of vitamin C and AFR were determined daily. On day 1, concentrations of vitamin C and AFR were measured at 0.25, 0.5, 1, 2, 4 and 8 h post infusion. Plasma concentrations of thiobarbituric acid-reactive substances (TBARS), tocopherol and urine concentrations of 8-oxoguanosine were determined on days 1 and 6. RESULTS: Kinetic studies on day 1 showed that concentrations of vitamin C and AFR displayed parallel dose- and time-dependent kinetics and elimination was highly efficient. Vitamin C and AFR fasting concentrations on days 2-6 were slightly above the baseline, suggesting new, stable steady states. TBARS decreased in both groups, whereas tocopherol and 8-oxoguanosine concentrations remained unchanged. CONCLUSION: Kinetics of AFR largely depend on plasma vitamin C concentrations and AFR is eliminated efficiently. Our data do not support induction of pro-oxidative effects in healthy volunteers given intravenous high-dose vitamin C. SPONSORSHIP: Pascoe Pharmazeutische Präparate GmbH, Giessen, Germany.

Carotenoids are decreased in biopsies from colorectal adenomas.

UNLABELLED: A lower intake of carotenoids is associated with an increased risk of colorectal cancer. In order to take advantage of the chemopreventive properties of carotenoids, it is necessary to determine carotenoid concentration at the target tissue. As early stages in the adenoma-carcinoma sequence of colorectal cancer might be susceptible to chemoprevention, we sought to determine carotenoid concentrations in biopsies from colorectal adenomas. METHODS: Biopsies from colorectal adenomas and non-involved mucosa were taken from seven patients. For controls, biopsies were obtained from the ascending and descending colon of patients without polyps (n = 5). Concentration of carotenoids (alpha-, beta-carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin) were determined by optimizing gradient HPLC-analysis. Results are expressed as pmol/microg DNA. RESULTS: Except for alpha-carotene, all carotenoids could reliably be detected in all specimens. In control patients carotenoid concentrations were highest in the ascending colon, being followed by the descending colon and non-involved mucosa from polyp-carriers. In colorectal adenomas all carotenoids were significantly reduced as compared to-non-involved mucosa (beta-carotene: 0.37 vs 0.19, P<0.03; lycopene: 0.34 vs 0.21, P<0.06, beta-cryptoxanthin: 0.14 vs 0.09, P<0.03, zeaxanthin: 0.18 vs 0.09, P<0.02; lutein: 0.18 vs 0.13,P <0.02). CONCLUSION: All carotenoids investigated are reduced in colorectal adenomas, suggesting that mucosal carotenoids could serve as biomarkers for predisposition to colorectal cancer. Moreover, anti-tumor activity exerted by carotenoids is limited due to mucosal depletion. We speculate that supplementation of a larger array of carotenoids might be beneficial for patients with colorectal adenoma.

[Acquired hemophilia A after an early abortion]. / Erworbene Hämophilie A nach Frühabort.

HISTORY: A 30-year-old woman was referred to our clinic because she had developed recurrent spontaneous hematomas of both calves within the last 2 months. 6 months earlier the patient had developed an ovarian hyperstimulation syndrome after ovarian stimulation treatment and intrauterine insemination. Shortly afterwards a missed abortion (8 (th) week) had been diagnosed. A curettage was carried out. INVESTIGATIONS: Routine coagulation tests confirmed a prolongation of aPTT to 90 s and a lupus anticoagulant. A high-titre factor VIII inhibitor (56 Bethesda units) was identified. TREATMENT AND COURSE: Given these facts an acquired post-partum hemophilia was diagnosed. The patient was treated with prednisolone and immunoglobulins. The aPTT shortened to normal values. The factor VIII inhibitor and lupus anticoagulant disappeared. There were no further hematomas. CONCLUSIONS: The simultaneous occurrence of antibodies in an altered immune state such as pregnancy is well known. In our case, acquired factor VIII inhibitor was found after an early abortion. Treatment with steroids and immunoglobulines led to the disappearance of factor VIII inhibitor and lupus anticoagulant.

Meta-analysis: efficacy of therapeutic regimens in ongoing variceal bleeding.

BACKGROUND AND STUDY AIMS: Variceal bleeding is a major cause of mortality in liver cirrhosis. Therapeutic options include medical (vasoconstrictive/vasoactive drugs) and endoscopic (sclerotherapy/ligation) treatments. Most studies evaluating acute esophageal bleeding have included patients with both ongoing and recent bleeding. Therefore therapeutic efficacy in ongoing bleeding may not have been adequately determined in these studies. A meta-analysis was performed for two reasons: first to compare directly the various treatments in the case of ongoing bleeding, as this would not be accomplished by a single trial, and secondly, to determine the success rates of each treatment option based on a larger number of patients. METHODS: An extensive Medline search identified 13 randomized controlled trials with precise statements of the number of patients with ongoing bleeding and their clinical outcomes. All studies followed a similar design and a Q test excluded heterogeneity of the studies. Data were pooled and cumulative success rates were calculated. RESULTS: Ligation appeared to be the most effective treatment (91.0 %, 95 % CI 82.4-96.3 %); it was significantly more successful than vasoconstrictive treatment (vasopressin/terlipressin 68.7 %, 61.7-75.2 %; P < 0.002, chi-squared-test) or vasoactive treatment (somatostatin/octreotide, 75.9 %, 68.1-82.6 %; P < 0.02) treatment, but was not statistically better than sclerotherapy (81.1 %, 71.7-88.4 %). The latter therapy was not statistically superior to medical treatment options. Calculations of estimated true effects, which take into account the weight of each study, rendered similar results. CONCLUSION: Ligation is the most effective treatment option. No significant difference was found between the efficacy of sclerotherapy and treatment with somatostatin or octreotide.