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Background and aims: Patients with gastric cancer often show signs of malnutrition. We sought to evaluate the influence of sarcopenia in patients with locally advanced, not metastasized, gastric or gastro-esophageal junction (GEJ) cancer undergoing curative treatment (perioperative chemotherapy and surgery) on morbidity and mortality in order to identify patients in need for nutritional intervention.
Patients and methods: Two-centre study, conducted in the Frankfurt University Clinic and Krankenhaus Nordwest (Frankfurt) as part of the University Cancer Center Frankfurt (UCT). 47/83 patients were treated in the FLOT trial (NCT01216644). Patients´ charts were reviewed for clinical data. Two consecutive CT scans were retrospectively analyzed to determine the degree of sarcopenia. Survival was calculated using the Kaplan-Meier method, multivariate analysis was performed using the Cox regression.
Results: 60 patients (72.3%) were male and 23 (27.7%) female. 45 patients (54.2%) had GEJ type 1–3 and 38 (45.8%) gastric tumors, respectively. Sarcopenic patients were significantly older than non-sarcopenic patients (mean age 65.1 years vs. 59.5 years, p = 0.042), terminated the chemotherapy significantly earlier (50% vs. 22.6%, p = 0.037) and showed higher Clavien-Dindo scores, indicating more severe perioperative complications (score ≥3 43.3 vs. 17.0%, p = 0.019). Sarcopenic patients had a significantly shorter survival than non-sarcopenic patients (139.6 ± 19.5 [95% CI, 101.3–177.9] vs. 206.7 ± 13.8 [95% CI, 179.5–233.8] weeks, p = 0.004). Multivariate Cox regression analysis showed that, besides UICC stage, sarcopenia significantly influenced survival.
Conclusion: Sarcopenia is present in a large proportion of patients with locally advanced gastric or GEJ cancer and significantly influences tolerability of chemotherapy, surgical complications and survival.
Background: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.
Methods: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period.
Results: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [−6.0 %, 19.8 %] does not include the lower noninferiority margin (−10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups.
Conclusion: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.
Prognostische Bedeutung der R1 Resektion : verbessertes Überleben in der Ära elektiver Chemotherapie
(2008)
Einleitung: Die Resektion kolorektaler Lebermetastasen ist der alleinigen Chemotherapie überlegen und erfolgt unter kurativer Zielsetzung. Multimodale Therapiekonzepte erlauben zunehmend primär irresektable Metastasen sekundär zu resezieren. Bei einem Teil der Patienten wird das Ziel der Tumorfreiheit nicht erreicht. Anhand einer retrospektiven Analyse wurde der Anteil der nicht kurativ resezierten Patienten nach primärer und sekundärer Resektion und ihr Überleben bestimmt. Material und Methoden: Bei 152 Patienten wurden zwischen 1/02 – 7/07 insgesamt 174 Leberresektionen aufgrund kolorektaler Metastasen durchgeführt. Dieses Kollektiv wurde anhand des R-Status der Leberresektion in eine kurativ- (Gruppe I) und in eine nicht kurativ resezierte Gruppe (Gruppe II) unterteilt. Die Auswertung erfolgte retrospektiv nach Überleben, Metastasenausdehnung, neoadjuvanter Chemotherapie und primärem Tumorstadium. Ergebnisse: 174 Leberresektionen schlossen 44 Re-Resektion und 6 zweizeitige Resektionen ein. Bei 61 Patienten erfolgte eine neoadjuvante Chemotherapie vor der Leberresektion. Die demographischen Daten beider Gruppen zeigten keinen signifikanten Unterschied (Gr. I: Männer: 60%, Alter: 63+/-1; Gr. II: Männer: 65%, Alter: 57+/-2,4). Die Anzahl der resezierten Metastasen war in Gruppe II signifikant höher (Gr. I: 1,5+/-0,1; Gr. II: 3,5+/-0,7, p<0,01), während die lokale Primärtumor-Ausdehnung gemessen am T-Stadium (Gr. I: 2,8 +/- 0,1, Gr. II: 2,8 +/- 0,13, n.s.) keinen Unterschied zeigte. Der Anteil der nicht kurativ resezierten Patienten war nach primärer und sekundärer Resektion gleich (17% vs. 21%, n.s.). Das Gesamtüberleben (4-Jahre, Kaplan-Meier) (Gr. I: 61%, Gr. II: 29%, p<0,05) und das mediane Überleben (Gr. I: 4,4, Gr. II: 2,4 [Jahre], p<0,05) wiesen einen signifikanten Unterschied auf. Schlussfolgerung: Der R-Status nach Resektion kolorektaler Lebermetastasen ist weiterhin ein entscheidender prognostischer Faktor. R-1 resezierte Patienten erreichen jedoch mit 2,4 Jahren ein besseres medianes Überleben als vergleichbare historische Kollektive. Sekundäre Resektionen nach neoadjuvanter Therapie weisen eine vergleichbar hohe Rate an R1 Resektionen auf wie bei primären Resektionen.
Background: Peritoneal metastasis is a common and dismal evolution of several gastrointestinal (GI) tumors, including gastric, colorectal, hepatobiliary, pancreatic, and other cancers. The therapy of peritoneal metastasis is largely palliative; with the aim of prolonging life and preserving its quality. In the meantime, a significant pharmacological advantage of intraperitoneal chemotherapy was documented in the preclinical model, and numerous clinical studies have delivered promising clinical results.
Methods: This is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy vs. intravenous systemic chemotherapy alone on patients with metastatic upper GI tumors with a peritoneal seeding. Upper GI-adenocarcinomas originated from biliary tract, pancreas and stomach, or esophago- gastric junction are eligible. Patients in the study are treated with standard of care systemic palliative chemotherapy (mFOLFOX6) vs. PIPAC with intravenous (i.v.) chemotherapy (mFOLFOX6). Patients in first line with first diagnosed peritoneal seeding are eligible. Primary outcome is progression free survival (PFS).
Conclusions: PIPAC-procedure is explicit a palliative method but it delivers cytotoxic therapy like in hyperthermic intraperitoneal chemotherapy (HIPEC)-procedure directly to the tumor in a minimally invasive technique, without the need for consideration of the peritoneal-plasma barrier. The technique of PIPAC is minimally invasive and very gentle and the complete procedure takes only round about 45 min and, therefore, optimal in a clearly palliative situation where cure is not the goal. It is also ideal for using this approach in a first line situation, where deepest response should be achieved. The symbiosis of systemic therapy and potentially effective surgery has to be well-planned without deterioration of the patient due to aggressive way of surgery like in cytoreductive surgery (CRS)+HIPEC.
Trial registration: EudraCT: 2018-001035-40.
BACKGROUND: Recent findings support the idea that interleukin (IL)-22 serum levels are related to disease severity in end-stage liver disease. Existing scoring systems--Model for End-Stage Liver Disease (MELD), Survival Outcomes Following Liver Transplantation (SOFT) and Pre-allocation-SOFT (P-SOFT)--are well-established in appraising survival rates with or without liver transplantation. We tested the hypothesis that IL-22 serum levels at transplantation date correlate with survival and potentially have value as a predictive factor for survival.
MATERIAL AND METHODS: MELD, SOFT, and P-SOFT scores were calculated to estimate post-transplantation survival. Serum levels of IL-22, IL-6, IL-10, C-reactive protein (CRP), and procalcitonin (PCT) were collected prior to transplantation in 41 patients. Outcomes were assessed at 3 months, 1 year, and 3 years after transplantation.
RESULTS: IL-22 significantly correlated with MELD, P-SOFT, and SOFT scores (Rs 0.35, 0.63, 0.56 respectively, p<0.05) and with the discrimination in post-transplantation survival. IL-6 showed a heterogeneous pattern (Rs 0.40, 0.63, 0.57, respectively, p<0.05); CRP and PCT did not correlate. We therefore added IL-22 serum values to existing scoring systems in a generalized linear model (GLM), resulting in a significantly improved outcome prediction in 58% of the cases for both the P-SOFT (p<0.01) and SOFT scores (p<0.001).
CONCLUSIONS: Further studies are needed to address the concept that IL-22 serum values at the time of transplantation provide valuable information about survival rates following orthotopic liver transplantation.
Background: Patient Blood Management (PBM) is a systematic quality improving clinical model to reduce anemia and avoid transfusions in all kinds of clinical settings. Here, we investigated the potential of PBM in oncologic surgery and hypothesized that PBM improves 2-year overall survival (OS).
Methods: Retrospective analysis of patients 2 years before and after PBM implementation. The primary endpoint was OS at 2 years after surgery. We identified a sample size of 824 to detect a 10% improvement in survival in the PBM group.
Results: The analysis comprised of 836 patients that underwent oncologic surgery, 389 before and 447 after PBM, was implemented. Patients in the PBM+ presented significantly more frequent with normal hemoglobin values before surgery than PBM− (56.6 vs. 35.7%; p < 0.001). The number of transfusions was significantly reduced from 5.5 ± 11.1 to 3.0 ± 6.9 units/patient (p < 0.001); moreover, the percentage of patients being transfused during the clinic stay was significantly reduced from 62.4 to 40.9% (p < 0.001). Two-year OS was significantly better in the PBM+ and increased from 67.0 to 80.1% (p = 0.001). A normal hemoglobin value (> 12 g/dl in female and > 13 g/dl in male) before surgery (HR 0.43, 95% CI 0.29–0.65, p < 0.001) was the only independent predictive factor positively affecting survival.
Conclusions: PBM is a quality improvement tool that is associated with better mid-term surgical oncologic outcome. The root cause for improvement is the increase of patients entering surgery with normal hemoglobin values.
Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates
(2021)
Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.
Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.
Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.
Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
Meeting Abstract : Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008 Einleitung: Konventionelle Ösophagusresektionen gehen auch heute noch mit einer hohe Morbidität und Mortalität einher. Die Ergebnisse einiger Serien minimal-invasiver Ösophagusresektionen sind vielversprechend, aber kontrovers diskutiert. Material und Methoden: Im Rahmen einer Beobachtungsstudie werden seit Mai 2005 minimal-invasive thorakoabdominelle Ösophagektomien mit cervikalem Magenhochzug durchgeführt. Die operativen Parameter und der postoperative Verlauf werden prospektiv erfasst und jetzt retrospektiv ausgewertet. Ergebnisse: Seit Mai 2005 wurden 28 Patienten minimal-invasive ösophagektomiert, 3 transhiatal und 25 thorakoabdominell. Indikation waren Plattenepithelkarzinome bei 14 und distale Adenokarzinome bei 13 Patienten, bei einem Patienten eine langstreckige benigne Stenose. Die Tumorstadien waren UICC-IIa in 7, UICC-2b in 2 und UICC-III in 18 Patienten. 11 Patienten (41%) wurden neoadjuvant vorbehandelt. Die OP-Zeit betrug im Mittel 296 Min. +/- 46 Min., der intraoperative Blutverlust 110 ml +/- 131 ml. Ein abdomineller Operationsabschnitt wurde konvertiert (4%), thorakal war bisher keine Konversion notwendig. R-0 Resektionen wurde in 26/27 Patienten (96%) erzielt, die mittlere Anzahl entfernter Lymphknoten betrug 19. Die 30-Tage –Letalität war 0, die Krankenhausletalität 11%. Die Morbidität betrug 54% und beinhaltet 7 Anastomoseninsuffizienzen, 2 „Ösophago“-tracheale Fisteln, 1 Hiatushernie, 2 Recurrensparesen, 2 Pneumonien und 1 beatmungspflichtiges Delir. Drei Patienten (11%) wurden operativ revidiert (eine Fistel, eine Anastomoseninsuffizienz bei Magenschlauchnekrose, eine Hiatushernie). Schlussfolgerung: Nach Einführung der minimal-invasiven thorakoabdominellen Ösophagektomie werden die exzellenten Ergebnisse anderer minimal-invasiver Serien bisher nicht erreicht, entsprechen aber im Wesentlichen den Ergebnissen der konventionellen Technik. Abzuwarten bleibt, ob die Ergebnisse nach weiterer Abflachung der Lernkurve Verbesserungen aufweisen werden.
Low platelet count predicts reduced survival in potentially resectable hepatocellular carcinoma
(2022)
The prognostic role of platelet count in hepatocellular carcinoma (HCC) remains unclear, and in fact both thrombocytopenia and thrombocytosis are reported as predictors of unfavourable outcomes. This study aimed to clarify the prognostic value of preoperative platelet count in potentially resectable HCC. We retrospectively reviewed 128 patients who underwent hepatic resection for HCC at a tertiary academic centre (2007–2019). Patient data were modelled by regression analysis, and platelet count was treated as a continuous variable. 89 patients had BCLC 0/A tumours and 39 had BCLC B tumours. Platelet count was higher in patients with larger tumours and lower in patients with higher MELD scores, advanced fibrosis, and portal hypertension (p < 0.001 for all listed variables). After adjusting for BCLC stage and tumour diameter, low platelet count associated with reduced overall survival (hazard ratio 1.25 per 50/nL decrease in platelet count, 95% confidence interval (CI) 1.02–1.53, p = 0.034) and increased perioperative mortality (odds ratio 1.96 per 50/nL decrease in platelet count, 95% CI 1.19–3.53, p = 0.014). Overall, low platelet count correlates with increased liver disease severity, inferior survival, and excess perioperative mortality in resectable HCC. These insights might be applied in clinical practice to better select patients for resection.
Local treatment of unresectable colorectal liver metastases : results of a randomized phase II trial
(2017)
Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach.
Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat.
Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm.
Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.