Biliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin ...and gemcitabine as adjuvant treatment in patients with resected BTC.
Patients initially received gemcitabine 1000 mg/m
alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m
and cisplatin 25 mg/m
on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.
Overall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.
Adjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.
The study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 ).
Purpose
Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine–chloroquine ...combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer.
Methods
In this 3 + 3 dose escalation study, patients received a single weekly standard dose of intravenous gemcitabine, followed by single weekly oral intake of 100, 200 or 300 mg of chloroquine. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Immune status was evaluated by RT-PCR to measure the relative expression of immune-related genes in peripheral blood mononuclear cells (PBMCs).
Results
Overall, nine patients median age 72 years; interquartile range (IQR), 68–78 years were treated. No dose-limiting toxicities as defined in the protocol were observed. Three patients experienced partial response, and two patients had stable disease. The median time to progression was 4 months (95% CI 0.8–7.2), and the median overall survival was 7.6 months (95% CI 5.3–9.9). Among 86 assayed immune genes, three were significantly differentially expressed in PBMCs from responding versus non-responding patients: interferon-gamma receptor-1, toll-like receptor 2, and beta-2 microglobulin.
Conclusions
The addition of chloroquine to gemcitabine was well tolerated and showed promising effects on the clinical response to the anti-cancer chemotherapy. Based on these initial results, the efficacy of the gemcitabine–chloroquine combination should be further assessed.
Purpose
The detection of small lung nodules in thoracoscopic procedure is difficult when the lesions are not located within the outer border of the lung. In the case of ground-glass opacities, it is ...often impossible to palpate the lesion. Marking lung nodules using a radiotracer is a known technique. We analysed the accuracy and safety of the technique and the potential benefits of operating in a hybrid operating room.
Methods
57 patients, including 33 (58%) females with a median age of 67 years (range 21-82) were included. In 27 patients, we marked and resected the lesion in a hybrid room. In 30 patients, the lesion was marked at the department of radiology the day before resection.
99m
TcTc-Macrosalb (Pulmocis
®
) was used at an activity of 1 MBq in the hybrid room and at an activity of 3 MBq the day before to get technical feasible results. Radioactivity was detected using the Neoprobe
®
detection system.
Results
Precise detection and resection of the nodules was possible in 95% of the lesions and in 93% of the patients. Complete thoracoscopic resection was possible in 90% of the patients. Total conversion rate was 10%, but conversion due to failure of the marking of the nodule was observed in only 5% of the patients. Histology revealed 28 (37%) primary lung cancers, 24 (32%) metastases and 21 (28%) benign lesions. In 13 (23%) patients, minor complications were observed. None of them required additional interventions.
Conclusion
The radio-guided detection of small pulmonary nodules is very accurate and safe after CT-guided injection of
99m
TcTc-Macrosalb. Performing the operation in a hybrid room has several logistic advantages and allows using lower technetium-99m activities. The technique allows minimally invasive lung sparing resection and prevents overtreatment of benign and metastatic lesions.
Prolonged air leak (PAL) is often associated with pain and immobilization and is a major limiting factor for discharge from the hospital. The efficacy of 2 surgical patches was investigated in the ...treatment of air leak following open surgery.
Forty-five patients were randomized in a 1:1 ratio either to treatment with Neoveil (polyglycolic acid) (n = 22) or TachoSil (collagen sponge) (n = 23). Air leak was monitored at 2, 4, 8, 12 and 24 h after surgery and then daily at 8 am and 6 pm, using a digital recording system. The primary outcome was the time to air leak closure. Secondary outcomes were incidence, air leak intensity, incidence of PAL and incidence of pneumonia.
Air leak 2 h after surgery was observed in 11/22 (50%) vs 14/23 (61%) patients treated with polyglycolic acid, respectively, with collagen sponge. On average, air loss within the first 24 h after surgery was lower and declined faster in patients treated with polyglycolic acid. Time to pulmonary air leak closure was somewhat shorter with polyglycolic acid (median interquartile range 10 2, 52 h) compared to collagen sponge (19 2, 141 h). However, the difference was not statistically significant (P = 0.35, Wilcoxon rank-sum test). PAL occurred in 3/22 (14%) vs 6/23 (26%) patients, and pneumonia occurred in 2/22 (9%) vs 3/23 (13%) patients treated with polyglycolic acid, respectively, collagen sponge.
Both systems are effective in the treatment of air leak. Our results suggest a possible superiority of Neoveil over TachoSil in post-surgery air leak control.
NCT04065880.
Abstract
OBJECTIVES
First experiences with rib fixation using nitinol, in terms of reliability and morbidity, influence on pain control and quality of life (QOL), in a large series of selected ...patients after blunt chest trauma.
METHODS
Data of all patients who had undergone rib fixation by the use of nitinol were retrospectively analysed in terms of indications, morbidity and in-hospital mortality. Pain status and health-related QOL were assessed preoperatively, when possible, at discharge and at 1, 3, 6 and 12 months post-surgery using visual analogous scale and short form 12 questionnaires.
RESULTS
From September 2017 to April 2019, 70 patients underwent rib fixation using the nitinol device, of which 47 (67%) had dislocated, painful fractures, 6 (8.5%) had flail chest injuries, 6 (8.5%) were emergencies with haemodynamical instability and 11 (16%) had pseudoarthrosis. Morbidity was 21% without wound infection; in-hospital mortality was 3%. Fracture of the material occurred in 6% of the patients during the first year, but removal of the material was not required. Analysis of the pain score showed a statistically significant decrease in pain for both the whole collective and the group with a series of dislocated and painful fractured ribs (P < 0.001, Tukey contrast on the linear mixed-effects models). Assessment of health-related QOL revealed a significant improvement in the physical score for the mid- and long-term analysis.
CONCLUSIONS
Our results suggest that rib fixation using the nitinol device is reliable, associated with an acceptable morbidity, while significantly decreasing pain and improving health-related QOL.
Treatment of rib fractures associated with blunt chest trauma is still commonly conservative 1.
Sternoclavicular joint infection is rare. Operation is the treatment of choice, but there is no generally accepted approach. This report evaluated the clinical and functional results after extended ...surgical treatment.
This single-center cohort study included 14 patients. Extended operation consisted of initial débridement with removal of the joint capsule; partial resection of the ipsilateral manubrium sterni, of the medial part of the clavicle, and sometimes of the first rib; and vacuum-assisted closure dressing. The procedure was repeated until the microbiologic findings and surgical site showed healing. Analysis of the risk factors, complications, and recurrence rate was performed. Functional results were assessed by the shortened version of the standardized Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire.
Only 4 of 14 patients (29%) had fever and elevated infectious parameters at diagnosis. Staphylococcus was the most frequently observed microorganism. Grade ≥III complications according to the Clavien-Dindo classification were observed in 5 of 14 (36%) patients. Recurrence was observed in 1 patient diagnosed 2 months after hospital discharge. Clinical and functional assessment after a mean follow-up of 48 months revealed excellent results without instability of the shoulder girdle, residual pain, or functional impairment. The mean QuickDASH score in our population was 4.5 of 100 points.
Extended surgical treatment of sternoclavicular joint infection in conjunction with assisted wound healing led to satisfying clinical and functional results.
Background: Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. ...The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma. Methods: Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m 2 gemcitabine and predefined doses of cisplatin 25 mg/m 2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1–14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported. Results: The determined MTD for gemcitabine was 800 mg/m 2 . Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1–49), and median progression-free survival 10.1 months (range 2–40). Conclusions: Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted.
•The use of vinorelbine with reduced-dose filgrastim resulted in high hematopoietic progenitor cell collection rates.•Leukapheresis sessions could be started at the anticipated collection date with ...high predictability.•Patients receiving less filgrastim reported lower bone pain intensity.•Treatment cost were lower in the study arm with reduced dose filgrastim.
Vinorelbine combined with filgrastim at a dose of 10 µg/kg of body weight (BW) per day is a reliable and well-tolerated regimen for mobilization of hematopoietic progenitor cells (HPCs) in patients with multiple myeloma. This prospective, randomized, phase II study was initiated to assess the feasibility of a reduced filgrastim dosage. Vinorelbine was combined with either standard-dose filgrastim (10 µg/kg BW per day) or reduced-dose filgrastim (5 µg/kg BW per day). Leukapheresis sessions were planned to start at day 8 and were continued until the predefined target amount of 4 × 106 HPCs/kg BW was collected. The study demonstrated the feasibility of vinorelbine combined with reduced daily filgrastim with a mean of 1.29 leukapheresis sessions necessary per patient (95% confidence interval, .95 to 1.7). All patients could start leukapheresis as planned at day 8, and the collection success rate was 100% for the whole patient collective after a maximum of 2 leukapheresis sessions. No statistically significant differences with regard to the amount of HPCs collected between the 2 groups were observed (P = .99). Accordingly, no differences were seen with regard to length of hospitalization for autotransplant (P = .34) and duration of neutrophil (P = .93) and platelet engraftment (P = .42). Patients receiving reduced-dose filgrastim reported significantly lower peak pain values in a numeric analogue scale (P = .01), and the costs were significantly lower than in patients undergoing standard-dose chemomobilization (P = .001). Vinorelbine 35 mg/m2 plus filgrastim 5 µg/kg BW once per day until completion of HPC collection is feasible and appears to be advantageous with respect to the severity of pain intensity and treatment costs.
EZH2 is a member of the polycomb group of genes and important in cell cycle regulation. Increased expression of EZH2 has been associated previously with invasive growth and aggressive clinical ...behavior in prostate and breast cancer, but the relationship with tumor cell proliferation has not been examined in human tumors. The purpose of this study was to validate previous findings in a population-based setting, also including tumors that have not been studied previously.
In our study of nearly 700 patients, we examined EZH2 expression and its association with tumor cell proliferation and other tumor markers, clinical features, and prognosis in cutaneous melanoma and cancers of the endometrium, prostate, and breast.
Strong EZH2 expression was associated with increased tumor cell proliferation in all four cancer types. Associations were also found between EZH2 and important clinicopathologic variables. EZH2 expression showed significant prognostic impact in melanoma, prostate, and endometrial carcinoma in univariate survival analyses, and revealed independent prognostic importance in carcinoma of the endometrium and prostate. CONCLUSION Our findings point at EZH2 as a novel and independent prognostic marker in endometrial cancer, and validate previous findings on prostate and breast cancer. Further, EZH2 expression was associated with features of aggressive cutaneous melanoma. The fact that EZH2 might identify increased tumor cell proliferation and aggressive subgroups in several cancers may be of practical interest because the polycomb group proteins have been suggested as candidates for targeted therapy. EZH2 expression should, therefore, be further examined as a possible predictive factor.
The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years ...2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0–19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20–64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.
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