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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 into 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.

Background Portal venous embolization (PVE) is a minimal invasive preoperative strategy that aims to increase future liver remnant (FLR) in order to facilitate extended hemihepatectomy. We analyzed our data retrospectively regarding complications and degree of hypertrophy (DH). Methods: 88 patients received PVE either by particles / coils (n = 77) or by glue / oil (n = 11), supported by 7 right hepatic vein embolizations (HVE) by coils or occluders. All complications were categorized by the Clavien- Dindo (CD) and the CIRSE classification. Results In 88 patients (median age 68 years) there was one intervention with a biliary leak and subsequent drainage (complication grade 3 CD, CIRSE 3), two with prolonged hospital stay (grade 2 CD, grade 3 CIRSE) and 13 complications grade 1 CD, but no complications of grade 4 or higher neither in Clavien- Dindo nor in CIRSE classification. The median relative increase in FLR was 47% (SD 35%). The mean pre-intervention standardized FLR rose from 23% (SD 10%) to a post-intervention standardized FLR of 32% (SD 12%). The degree of hypertrophy (DH) was 9,3% (SD 5,2%) and the kinetic growth rate (KGR) per week was 2,06 (SD 1,84). Conclusion PVE and, if necessary, additional sequential HVE were safe procedures with a low rate of complications and facilitated sufficient preoperative hypertrophy of the future liver remnant.

Cancer cachexia has been linked to gut bacterial alterations, but alterations of gut viruses, mostly bacteriophages, have not yet been explored. We performed shotgun metagenomic sequencing of DNA from stool samples of 78 cachectic and 42 non-cachectic cancer patients. K-mer-based matching to reference databases revealed abundance variations of bacteria and viruses. Beyond bacterial alterations, cachectic patients exhibited significantly lower bacteriophage abundance, predominantly affecting Caudovirales and Siphoviridae species (double-stranded DNA) but also Inoviridae and Microviridae families (single-stranded DNA). Machine learning models exploiting the data for classification between cachectic and non-cachectic state yielded an AUC of 0.704. Caudovirales and Siphoviridae species were among the top-most important classifiers. AUC increased to 0.850 with solely antibiotic-exposed samples from 20 cachectic and 10 non-cachectic patients. This study is the first to suggest a link between cancer cachexia and intestinal bacteriophage richness. This could constitute a new basis for hypothesis-driven research in cancer cachexia diagnosis and treatment.

Introduction. Percutaneous hepatic perfusion with melphalan (PHP-M) for hepatic metastasis of uveal melanoma (LMUM) achieves high local response rates, but the individual clinical benefit is poorly defined. We aimed to determine cofactors of response and clinical outcomes including the probability of long-term (5-years) overall survival (OS) in PHP-M-treated patients with LMUM. Patients and Methods. We retrospectively reviewed clinicopathological, radiological, and outcome data of 19 patients with unresectable LMUM treated with 43 PHP-M (median 2 PHP-M) between 2014 and 2019. Tumor response and adverse events were evaluated using RECIST 1.1 and the Clavien–Dindo classification. Kaplan–Meier methods and Cox regression hazard proportional models were used. Results. Of 19 patients, 10 (53%) achieved a partial response (PR) and 9 (47%) had stable disease (SD). There was no progressive disease (PD) and no adverse events exceeding Clavien–Dindo grade IV. Median OS was 16.7 months after the first PHP-M treatment and 26.4 months after initial diagnosis. Low hepatic tumor volume (median of 10 mL vs. 150 mL) was an independent predictor of favorable OS (hazard ratio (95% confidence interval): 0.190 (0.041, 0.893); p<0.05), and female patients were at a lower risk compared with males (0.146 (0.017, 1.240)). Estimates of the overall survival were 0.213 (0.0449, 1) from first imaging (95% confidence interval) to 5 years and 0.793 (0.609, 1) and 0.604 (0.380, 0.960) for 1 and 2 years after chemosaturation, respectively. Discussion. PHP-M for nonresectable LMUV provides a safe and locally efficient liver-directed procedure that offers patients a chance for long-term OS, especially for patients with a low hepatic tumor burden.

Background The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. Objective To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. Design Prospective cohort study. Setting Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. Patients The first 12 consecutive COVID-19-positive deaths. Measurements Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. Limitation Limited sample size. Conclusion The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. Primary funding source University Medical Center Hamburg-Eppendorf.

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.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.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).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.

Background: Acute myocardial injury (AMJ), assessed by elevated levels of cardiac troponin, is associated with fatal outcome in coronavirus disease 2019 (COVID-19). However, the role of acute cardiovascular (CV) events defined by clinical manifestation rather than sole elevations of biomarkers is unclear in hospitalized COVID-19 patients. Objective: The aim of this study was to investigate acute clinically manifest CV events in hospitalized COVID-19 patients. Methods: From 1 March 2020 to 5 January 2021, we conducted a multicenter, prospective, epidemiological cohort study at six hospitals from Hamburg, Germany (a portion of the state-wide 45-center CORONA Germany cohort study) enrolling all hospitalized COVID-19 patients. Primary endpoint was occurrence of a clinically manifest CV-event. Results: In total, 132 CV-events occurred in 92 of 414 (22.2%) patients in the Hamburg-cohort: cardiogenic shock in 10 (2.4%), cardiopulmonary resuscitation in 12 (2.9%), acute coronary syndrome in 11 (2.7%), de-novo arrhythmia in 31 (7.5%), acute heart-failure in 43 (10.3%), myocarditis in 2 (0.5%), pulmonary-embolism in 11 (2.7%), thrombosis in 9 (2.2%) and stroke in 3 (0.7%). In the Hamburg-cohort, mortality was 46% (42/92) for patients with a CV-event and 33% (27/83) for patients with only AMJ without CV-event (OR 1.7, CI: (0.94–3.2), p = 0.077). Mortality was higher in patients with CV-events (Odds ratio(OR): 4.8, 95%-confidence-interval(CI): [2.9–8]). Age (OR 1.1, CI: (0.66–1.86)), atrial fibrillation (AF) on baseline-ECG (OR 3.4, CI: (1.74–6.8)), systolic blood-pressure (OR 0.7, CI: (0.53–0.96)), potassium (OR 1.3, CI: (0.99–1.73)) and C-reactive-protein (1.4, CI (1.04–1.76)) were associated with CV-events. Conclusion: Hospitalized COVID-19 patients with clinical manifestation of acute cardiovascular events show an almost five-fold increased mortality. In this regard, the emergence of arrhythmias is a major determinant.

Das hepatozellulare Karzinom (HCC) wird zu einer immer groser werdenden soziookonomischen Herausforderung. Internationale Leitlinien sprechen sich vorwiegend gegen die pratherapeutische Bestimmung der α‑Feto-Protein(AFP)-Konzentration aus. Bezuglich der prognostischen Aussagekraft des AFP ist die europaische Studienlage nicht aussagekraftig genug. Diese Arbeit soll mogliche Aspekte des AFP-Spiegels aufzeigen und die prognostische Vorhersagekraft des AFP-Spiegels untersuchen sowie Anregungen fur zukunftige prospektive Studien geben. Eine prospektive Leberdatenbank (n = 1382) wurde im Hinblick auf HCC-Patienten, die einen histologisch gesicherten Tumor aufweisen (n = 92), ausgewertet. Es lagen Informationen zu T‑, N‑, M‑, G‑Stadium und R‑Status bzw. zu Geschlecht, Alter, Genese vor. Fur die Analyse teilten wir das Patientengut anhand von 3 Cut-off-Werten in 6 Gruppen ein. Des Weiteren fuhrten wir eine Uberlebensanalyse mittels Kaplan-Meier und eine multifaktorielle Analyse der Einflussfaktoren auf das Outcome durch. Es gibt einen statistisch signifikanten Zusammenhang zwischen dem AFP-Spiegel, dem Tumordurchmesser (T1/2 vs. T3/4) und dem Grading (G1/G2 vs. G3/G4). In allen Gruppen fiel die Uberlebensprognose in der jeweiligen Gruppe mit dem hoheren AFP-Spiegel signifikant schlechter aus (p 8 μg/l betrug 35 Monate; bei Patienten mit AFP-Spiegeln von >200 μg/l bzw. >400 μg/l betrug das mediane Uberleben 15 Monate bzw. 11 Monate. Hohe AFP-Spiegel sind unabhangig vom T‑Stadium, Alter und R‑Status des Patienten im Vergleich zu niedrigen AFP-Spiegeln ein signifikanter Einflussfaktor fur das Outcome. Unter Berucksichtigung der vorliegenden Ergebnisse kann dem AFP-Spiegel eine therapeutische Nutzlichkeit zugeschrieben werden. Es konnten sich aus der Hohe der gemessenen AFP-Konzentration therapeutische Konsequenzen im Hinblick auf die Therapiestrategie ergeben. Demnach empfehlen wir bei allen HCC-Patienten die pra- und postoperative Bestimmung des AFP-Spiegels.

Since December 2020, the COVID-19 pandemic in Germany was influenced by two new major factors: detection of new virus Variants of Concern (VOC) and the start of the vaccination campaign...

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.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.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.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.Study registered with clinicaltrials.gov : NCT01522209.

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.

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.

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.

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.

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. 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. 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. 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.

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.

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.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 index0.1). 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.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; p0.05; 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; p0.05; respectively).Sulfur hexafluoride-filled microbubble-enhanced sonography improves characterization of focal splenic lesions with and without the availability of clinical data.

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

Modern colorectal liver metastasis (CRLM) surgery has undergone a very impressive development over the last ten years due to the evolution of methods, techniques and extension of surgical indications. The main limits of surgical CRLM treatment were extension of liver disease, volume and quality of future liver remnant and foreseeable hypertrophy induced by portal vein embolisation or ligation (PVE/PVL) for a possible two-staged hepatectomy. In 2007 Dr. Schlitt, performing the first associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) [1], unconsciously opened Pandora’s box; leading to intense surgical research into two-staged hepatectomies and allowing a further expansion of the resectable pool of liver tumour patients affected by bilobar tumour load. Now, 9 years after the first ALPPS, and after the recently proposed technical evolution named “monosegment ALPPS” [2], we can affirm that we are about to abandon a dogma of liver surgery: for extended liver resection at least 2 liver segments as future liver remnant are necessary; in fact, now this seems to no longer be true. This recent advancement further enhances the concept of liver hypertrophy and the application of ALPPS after agreements of the first consensus meeting [1]. As

Ziel: Die Ultraschall (US)-gesteuerte Radiofrequenzabalation (RFA) wird zunehmend zur Behandlung von Lebertumoren eingesetzt. Ziel der vorliegenden Studie war, den Einfluss einer interdisziplinaren Indikationsstellung auf die klinischen Ergebnisse zu untersuchen. Material und Methoden: Von Januar 2002 bis Dezember 2004 wurden 69 konsekutive Patienten zur RFA-Behandlung vorgestellt. Nach interdisziplinarer Tumorboard-Entscheidung wurden 33 Patienten (47,8 %) mit 70 Lebertumoren mittels 14-gauge Nadelelektroden uber einen perkutanen (33) oder intraoperativen Zugangsweg (7) allein oder kombiniert mit einer Resektion (3) oder Chemoembolisation (3) behandelt. 36 Patienten (52,2 %) wurden von der RFA-Behandlung ausgeschlossen, uberwiegend wegen zu groser Tumorlast oder Nichtansprechen auf vorrausgegangene Chemotherapie. Alle 69 Patienten wurden im Mittel 20 Monate (6 - 42 Monate) nachbeobachtet, um den klinischen Verlauf zu erfassen, die 33 behandelten Patienten zusatzlich mittels Kontrastmittel-CT zur Beurteilung des lokalen Behandlungserfolgs. Ergebnisse: Eine komplette Tumornekrose wurde bei 64/70 abladierten Lasionen (91,4 %) erreicht. Das Verhaltnis von Herdgrose zu Nekrose betrug im Mittel 2,3 cm (0,9 - 5,0) vs. 3,7 cm (2,1 - 5,7). Bei 2 Patienten (6,6 %) traten Komplikationen auf, darunter ein Postablationsyndrom und ein Leberabzess. Zum Zeitpunkt der Tumorboard-Entscheidung unterschieden sich die RFA- (33) und Nicht-RFA-Gruppe (36) insbesondere im mittleren Tumordurchmesser (2,3 vs. 3,5 cm), der Zahl der Lasionen pro Patient (2,1 vs. 3,8), und der Resistenz gegen Chemotherapie (2/33 vs. 22/36). 24/36 der von uns fur ungeeignet beurteilten Patienten (66,6 %) wurden auswarts mittels RFA behandelt. Die Uberlebenszeiten von in unserer Institution (33) vs. auswarts behandelten (24) vs. nicht behandelten Patienten (12) waren unterschiedlich; 1/33 (3 %) vs. 9/24 (37,5 %) vs. 8/12 (66,6 %) verstarben innerhalb von 6 Monaten und 27/33 (81,2 %) vs. 5/24 (29,2 %) vs. 2/12 (16,7 %) uberlebten bei mittlerer Nachbeobachtungzeit von 20 Monaten. Schlussfolgerung: Die US-gesteuerte RFA ist eine sichere lokaltherapeutische Option zur Destruktion kleiner Lebertumore (< 3 cm). Sorgfaltig interdisziplinar ausgewahlte Patienten konnen profitieren, der unkritische Einsatz fuhrt zu unbefriedigenden klinischen Behandlungsergebnissen. Purpose: Ultrasonography (US)-guided Radiofrequency ablation (RFA) is increasingly used to treat liver tumours. The aim of this study was to evaluate the impact of multidisciplinary patient selection on clinical results. Materials and Methods: From January 2002 to December 2004, 69 consecutive patients with malignant hepatic tumours were presented to our clinic for RFA-treatment. After a multidisciplinary tumour board decision, 33 patients (47.8 %) with 70 liver tumours underwent RFA using a 14-gauge needle electrode via a percutaneous (26) or surgical (7) approach, either alone or combined with resection (3) or chemoembolisation (3). 36 patients (52.2 %) were excluded from RFA treatment, mainly because of extensive disease or failure of prior chemotherapy. With a median of 20 months (range 6 - 42 months), all 69 patients were followed clinically to assess survival, and the 33 patients who received additional treatment were examined by contrast-enhanced CT to assess local success. Results: Complete necrosis was obtained in 64/70 of ablated tumours (91.4 %).The corresponding mean sizes (ranges) of lesion vs. necrosis achieved were 2.3 cm (0.9 - 5.0) vs. 3.7 cm (2.1 - 5.7). Two complications (6.6 %) occurred, including one liver abscess and one postablational syndrome. At the time of the tumour board decision, the RFA (33) and non-RFA (36) group differed in mean sizes of tumours (2.3 vs. 3.5 cm), average tumours per patient (2.1 vs. 3.8), and failure of prior chemotherapy (2/33 vs. 22/36). From 36 patients judged to be ineligible for RFA, 24 (66.6 %) underwent RFA at another institution. When comparing survival of patients who underwent RFA at our institution (33) vs. those who underwent RFA outside (24) vs. those who underwent no RFA (12), 1/33 (3 %) vs. 9/24 (37.5 %) vs. 8/12 (66.6 %) died within 6 month and 27/33 (81.2 %) vs. 5/24 (29.2 %) vs. 2/12 (16.7 %) were alive after 20 months median follow up. Conclusion: US-guided RFA offers a safe local treatment option to destroy small liver tumours (< 3 cm). Carefully and multidisciplinary selected patients may derive benefit, but uncritical application leads to unsatisfying clinical results.

ABSTRACT 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.

Anamnese und klinischer Befund: Eine 46-jahrige Patientin stellte sich mit seit 8 Wochen zunehmenden, morphinresistenten, zur Immobilitat fuhrenden Schmerzen im Bereich des rechten Sitzbeins vor. Nach intensiver und kompliaktionsreicher Vorbehandlung eines Ovarial- und Rektumkarzinom inklusive einer Beckenvorbestrahlung bis zu einer Herddosis von 70,4 Gy lehnte die Patientin eine erneute Operation, Strahlentherapie oder Chemotherapie ab. Untersuchungen: Die Knochenszintigraphie ergab eine Mehranreicherung im rechten Sitzbein. Das konventionelle Rontgen zeigte hier eine 3 × 4 cm grose Auftreibung mit Kortikalisausloschung. Die Computertomographie wies zahlreiche Mikrofrakturen und pseudarthrotische Veranderungen nach. Per Nadelbiopsie wurde eine Knochenmetastase des Rektumkarzinoms verifiziert. Die Prufung der Vorbestrahlungsfelder ergab ein hohes Risiko fur einen Bestrahlungsschaden bei konventioneller Fraktionierung. Therapie und Verlauf: Im interdisziplinaren Konsens erfolgte bei eingeschrankter Einsatzmoglichkeit von Standardverfahren eine perkutane Radiofrequenzablation mit nachfolgender Knochenzementauffullung. Der Eingriff wurde komplikationslos in einer Sitzung unter Analgosedierung und computertomographischer Nadelpositionierung durchgefuhrt. Nach 8 Tagen konnte die Patientin unter Morphinreduktion schmerzfrei mobilisiert entlassen werden, der Karnofsky-Index stieg von 30 % auf 90 %. Nach 9 Monaten anhaltender Schmerzfreiheit und Belastungsstabilitat traten neu Lungenmetastasen auf. Die Sitzbeinmetastase zeigte nativradiologisch keinen Tumorprogress, die Lage des Knochenzements war unverandert regelrecht. Einer erneuten Chemotherapie stimmte die Patientin jetzt zu. Folgerung: Die perkutane, kombinierte Radiofrequenzablation und Osteoplastie fuhrt im Einzelfall zur schnellen Wiederherstellung von Lebensqualitat und Mobilitat. Nutzen und Risiko der palliativen, minimal-invasiven Lokaltherapie von symtomatischen Knochenmetastasen sollten durch Studien objektiviert werden, speziell fur Patienten, bei denen Standardverfahren wie Strahlentherapie oder Operation ausscheiden oder versagen. History and admission findings: A 46-year-old woman presented with worsening, morhine-resistant pain during the previous 8 weeks in the right ischium which rendered her immobile. The patient refused further surgery, radiotherapy or chemotherapy, as she had been treated for ovarial cancer and recurring rectal carcinoma with peritoneal carcinomatosis for the last three years almost without interruption and experiended several complications. The pelvic region had radiotherapy up to 70,4 Gy. Investigation: Scintigraphy of the bone showed enhancement in the right ischium. Conventional radiography demonstrated an irregular lesion with destruction of the corticalis 3 × 4 cm in size. Computed tomography revealed numerous microfractures and pseudoarthrotic changes. Needle biopsy confirmed a bone metastasis from the rectal carcinoma. Examination of radiation fields showed a high risk for radiation damage using conventional fractionation. Treatment and course: After achieving an interdisciplinary consensus the metastatic lesion of the patient under analgesia and sedation was thermoablated by using radiofrequency percutanously under ct-control and filled with bone cement. 8 days later the patient was released from hospital pain-free and mobile. Her Karnofsky index rose from 30 % to 90 %. Morphine could be reduced to zero. No complications occurred. 9 month later, though newly appearing lung metastasisis, the lesion of the ischium was still asymptomatic and stable and conventional radiography did not indicate local tumorprogress or dislocated bone cement. The patient now agreed to further chemotherapy. Conclusion: Palliative minimally invasive radiofrequency ablation with concurrent osteoplasty can be effective in individual cases giving a better quality of life and mobility. Benefits and risks should be carefully evaluated in studies examing quality of life, especially in patients without the options of surgical and radiotherapy.

Die Qualitat der diagnostischen und interventionellen Sonographie der Leber wird fur onkologische Patienten durch den Einsatz von Ultraschallkontrastmitteln erheblich gesteigert. Die Diagnose von Leberherden, der Nachweis von Lebermetastasen und die Prazision von ultraschallgezielten Interventionen (Punktion, Radiofrequenzablation) werden deutlich verbessert. Die Kontrastmittel-Sonographie ist die primare Methode zum Staging und zur Verlaufskontrolle fur uberwiegend hepatisch metastasierende Malignome (z.B. gastrointestinale Tumore). Ohne Kontrastmittelsonographie ist der sonographische Ausschlus von Lebermetastasen bei differentialtherapeutischer Konsequenz nicht mehr vertretbar (z. B. kolorektale Lebermetastasen). Die notwendige Ausbildung und Qualitat der Untersucher wird durch das Mehrstufenmodell der DEGUM (Deutsche Gesellschaft fur Ultraschall in der Medizin) gewahrleistet.

After the establishment of DNA/RNA sequencing as a means of clinical diagnosis, the analysis of the proteome is next in line. As a matter of fact, proteome-based diagnostics is bound to be even more informative, since proteins are directly involved in the actual cellular processes that are responsible for disease. However, the structural variation and the biochemical differences between proteins, the much wider range in concentration and their spatial distribution as well as the fact that protein activity frequently relies on interaction increase the methodological complexity enormously, particularly if an accuracy and robustness is required that is sufficient for clinical utility. Here, we discuss the contribution that protein microarray formats could play towards proteome-based diagnostics.

Endoscopic mucosal resection (EMR) or radical surgical resection are the standard treatment options for patients with early Barrett´s adenocarcinoma (EBAC). Endoscopic submucosal dissection (ESD) is a new endoscopic technique, which allows—in contrast to EMR—endoscopic en-bloc resection of neoplastic lesions greater than 2 cm with complete histological evaluation of the resected specimen. In contrast to Western countries, Barrett´s esophagus is less common in Asia indicating the low volume of published data of ESD in EBAC in Japanese series. Therefore, the aim of the present study is to describe the results of ESD in patients with EBAC performed in a German tertiary referral center. Between November 2009 and April 2014 ESDs were performed in 22 patients with histologically proven EBAC. Data were given for the en-bloc, the R0, the R0 en-bloc, and the curative resection rate as well as for the complication and the local recurrence rate. ESD was technically possible in all of the 22 patients. 20 of the resected EBAC were mucosal carcinomas, whereas in two patients the tumor showed submucosal invasion. The en-bloc, R0, R0 en-bloc, and curative resection rates were 95.5, 81.8, 81.8 %, and77.3 %, resp. Complication rate was 27.3 % (perforation n = 1, bleeding n = 2, stenosis n = 3). In case of curative tumor resection, only one local tumor recurrence (5.9 %) occurred after a medium follow-up of 1.6 years. Despite the small number of patients and a relatively short follow-up, the present data underline the value of ESD, especially in case of curative resections in the definite and less invasive therapy of EBAC. Attention should be drawn toward subsquamous extension of EBAC requiring a sufficient safety margin as an obligate condition for curative R0 resections. Due to the required learning curve and the management of potential complications, ESD should be restricted to greater endoscopic centers.

Paraneoplastic symptoms can manifest in a multitude of organ systems and can precede cancer diagnosis, accompany the acute disease or appear during remission. Paraneoplastic neurological syndromes ...

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.

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.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.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 cmCofactors 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.

Zusammenfassung Ziel: Ziele dieser Arbeit waren die Identifikation und die Validierung von unterschiedlichen tumorspezifischen Kontrastmittelmustern für die Differenzialdiagnose zwischen benignen vaskulären Neoplasien (Typ Hämangiom/Hamartom) und malignen Milzherden in der Kontrastmittelsonografie (CEUS). Material und Methoden: 136 Milzläsionen (58 benigne vaskuläre Neoplasien, 78 maligne Läsionen) wurden jeweils in der B-Bild-Sonografie (US) und nachfolgend in der Kontrastmittelsonografie nach Sulfur-Hexafluoride-Injektion untersucht und dokumentiert. Zwei On-site-Reader analysierten das Kontrastmittelverhalten der Milzläsionen während der arteriellen und parenchymalen Phase. Mittels univariater und multivariater Analyse wurden tumorspezifische Kontrastmittelmuster, die signifikant mit einer der beiden Tumordiagnosen korreliert waren, identifiziert. Zwei geblindete Off-site-Reader benutzten diese tumorspezifischen Kontrastmittelmuster als Diagnosekriterien und stellten unabhängig voneinander anhand der Befunde der B-Bild-Sonografie und der Kontrastmittelsonografie eine Diagnose der Milzherde. Die diagnostische Treffsicherheit und Confidence (Az-Werte) sowie die Übereinstimmung der Off-site-Reader (қ-Werte) wurden kalkuliert. Referenzstandards waren Histopathologie oder CT und/oder MRI mit klinischem Verlauf. Ergebnisse: In der multivariate Analyse waren arterielles Hyper- oder Isoenhancement unabhängige Prediktoren für eine benigne vaskuläre Neoplasie (Odds Ratio, 3,558; p Schlussfolgerung: Die Kontrastmittelsonografie verbessert die Differenzialdiagnose zwischen benigen vaskulären Neoplasien und malignen Tumoren in der Milz und scheint besonders hilfreich bei unklaren, zufällig im Ultraschall entdeckten hypoechogenen Milzherden.

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.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.The reference standard verified 109 (45or = 1 cm) hepatic lesions in 25 patients, including 65 (25or = 1 cm) metastases in 16 patients (M1). Regarding the 45or = 1 cm liver lesions, rates for detection were significantly higher (P0.05) 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 P0.05). On patient-based analysis, specificity of MDCT (85.4%, 41/48) was significantly lower (P0.05) 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 (P0.05) 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 (P0.05) 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).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.

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