Search

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.

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

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.

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.