Carcinogenicity Evaluation of Baclofen in TgrasH2 Mice

Baclofen is a γ-aminobutyric acid-B receptor agonist used for control of spastic muscle activity and as a treatment for alcohol abuse. The review of the nonclinical database suggested a data gap for potential carcinogenicity following long-term use. Regulatory requirements for pharmaceutical safety testing of cancer-causing potential have historically included 2-year rodent studies in rats and mice. The availability of transgenic models with greater specificity and sensitivity to carcinogens provides safety testing alternatives that align with the 3Rs. The carcinogenicity of baclofen was evaluated in CB6F1-TgrasH2 transgenic mice following daily oral administration at 45, 90, and 180 mg/kg/d for 26 weeks, preceded by a 2-week drug-conditioning period. There were no treatment-related palpable masses or neoplastic findings, and survival rates were not affected by the baclofen treatment. In conclusion, baclofen was considered as noncarcinogenic in CB6F1-TgrasH2 mice, which is consistent with results previously obtained in a 2-year rat study.

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Transapical versus Conventional Aortic Valve Replacement�A Propensity-Matched Comparison

The Heart Surgery Forum ◽

10.1532/hsf98.20111084 ◽

2012 ◽

Vol 15 (1) ◽

pp. 4 ◽

Cited By ~ 23

Author(s):

David M. Holzhey ◽

William Shi ◽

A. Rastan ◽

Michael A. Borger ◽

Martin H�nsig ◽

...

Keyword(s):

Aortic Valve ◽

Survival Rates ◽

Long Term Results ◽

Term Survival ◽

Kaplan Meier ◽

Risk Patients ◽

Short And Long Term ◽

Good Treatment Option ◽

Matched Comparison

Introduction: The goal of this study was to compare the short- and long-term outcomes after aortic valve (AV) surgery carried out via standard sternotomy/partial sternotomy versus transapical transcatheter AV implantation (taTAVI).Patients and Methods: All 336 patients who underwent taTAVI between 2006 and 2010 were compared with 4533 patients who underwent conventional AV replacement (AVR) operations between 2001 and 2010. Using propensity score matching, we identified and consecutively compared 2 very similar groups of 167 patients each. The focus was on periprocedural complications and long-term survival.Results: The 30-day mortality rate was 10.8% and 8.4% (P = .56) for the conventional AVR patients and the TAVI patients, respectively. The percentages of postoperative pacemaker implantations (15.0% versus 6.0%, P = .017) and cases of renal failure requiring dialysis (25.7% versus 12.6%, P = .004) were higher in the TAVI group. Kaplan-Meier curves diverged after half a year in favor of conventional surgery. The estimated 3-year survival rates were 53.5% � 5.7% (TAVI) and 66.7% � 0.2% (conventional AVR).Conclusion: Our study shows that even with all the latest successes in catheter-based AV implantation, the conventional surgical approach is still a very good treatment option with excellent long-term results, even for older, high-risk patients.

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Pulmonary Homografts for Aortic Valve Replacement: Long-term Comparison with Aortic Grafts

The Heart Surgery Forum ◽

10.1532/hsf98.20101162 ◽

2011 ◽

Vol 14 (4) ◽

pp. 237 ◽

Cited By ~ 3

Author(s):

Ferdinand Vogt ◽

Anke Kowert ◽

Andres Beiras-Fernandez ◽

Martin Oberhoffer ◽

Ingo Kaczmarek ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Survival Rates ◽

Long Term Results ◽

Rank Test ◽

Aortic Graft ◽

Valve Prostheses ◽

Retrospective Comparative Study

Objective: The use of homografts for aortic valve replacement (AVR) is an alternative to mechanical or biological valve prostheses, especially in younger patients. This retrospective comparative study evaluated our single-center long-term results, with a focus on the different origins of the homografts.Methods: Since 1992, 366 adult patients have undergone AVR with homografts at our center. We compared 320 homografts of aortic origin and 46 homografts of pulmonary origin. The grafts were implanted via either a subcoronary technique or the root replacement technique. We performed a multivariate analysis to identify independent factors that influence survival. Freedom from reintervention and survival rates were calculated as cumulative events according to the Kaplan-Meier method, and differences were tested with the log-rank test.Results: Overall mortality within 1 year was 6.5% (21/320) in the aortic graft group and 17.4% (8/46) in the pulmonary graft group. In the pulmonary graft group, 4 patients died from valve-related complications, 1 patient died after additional heterotopic heart transplantation, and 1 patient who entered with a primary higher risk died from a prosthesis infection. Two patients died from non-valve-related causes. During the long-term follow-up, the 15-year survival rate was 79.9% for patients in the aortic graft group and 68.7% for patients in the pulmonary graft group (P = .049). The rate of freedom from reoperation was 77.7% in the aortic graft group and 57.4% in the pulmonary graft group (P < .001). The reasons for homograft explantation were graft infections (aortic graft group, 5.0%; pulmonary graft group, 6.5%) and degeneration (aortic graft group, 7.5%; pulmonary graft group, 32.6%).Conclusion: Our study demonstrated superior rates of survival and freedom from reintervention after AVR with aortic homografts. Implantation with a pulmonary graft was associated with a higher risk of redo surgery, owing to earlier degenerative alterations.

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Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

Orvosi Hetilap ◽

10.1556/650.2015.30260 ◽

2015 ◽

Vol 156 (45) ◽

pp. 1824-1833 ◽

Cited By ~ 1

Author(s):

Árpád Illés ◽

Ádám Jóna ◽

Zsófia Simon ◽

Miklós Udvardy ◽

Zsófia Miltényi

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Treatment Options ◽

Survival Rates ◽

Relapse Free Survival ◽

Term Survival ◽

Free Survival ◽

Novel Treatment ◽

Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

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Herbal Medicine for Glioblastoma: Current and Future Prospects

Medicinal Chemistry ◽

10.2174/1573406416666200130100833 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1022-1043

Author(s):

Imran Khan ◽

Sadaf Mahfooz ◽

Mustafa A. Hatiboglu

Keyword(s):

Cell Proliferation ◽

Survival Rates ◽

Standard Of Care ◽

Natural Compounds ◽

Treatment Modalities ◽

Normal Brain ◽

The Central Nervous System ◽

Cycle Regulation ◽

Immense Potential

Background: Glioblastoma is one of the most aggressive and devastating tumours of the central nervous system with short survival time. Glioblastoma usually shows fast cell proliferation and invasion of normal brain tissue causing poor prognosis. The present standard of care in patients with glioblastoma includes surgery followed by radiotherapy and temozolomide (TMZ) based chemotherapy. Unfortunately, these approaches are not sufficient to lead a favorable prognosis and survival rates. As the current approaches do not provide a long-term benefit in those patients, new alternative treatments including natural compounds, have drawn attention. Due to their natural origin, they are associated with minimum cellular toxicity towards normal cells and it has become one of the most attractive approaches to treat tumours by natural compounds or phytochemicals. Objective: In the present review, the role of natural compounds or phytochemicals in the treatment of glioblastoma describing their efficacy on various aspects of glioblastoma pathophysiology such as cell proliferation, apoptosis, cell cycle regulation, cellular signaling pathways, chemoresistance and their role in combinatorial therapeutic approaches was described. Methods: Peer-reviewed literature was extracted using Pubmed, EMBASE Ovid and Google Scholar to be reviewed in the present article. Conclusion: Preclinical data available in the literature suggest that phytochemicals hold immense potential to be translated into treatment modalities. However, further clinical studies with conclusive results are required to implement phytochemicals in treatment modalities.

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Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis

Leukemia ◽

10.1038/s41375-020-01111-2 ◽

2021 ◽

Author(s):

Hagop M. Kantarjian ◽

Timothy P. Hughes ◽

Richard A. Larson ◽

Dong-Wook Kim ◽

Surapol Issaragrisil ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Survival Rates ◽

Chronic Phase ◽

Individual Treatment ◽

Molecular Response ◽

Newly Diagnosed ◽

Long Term Outcomes ◽

Treatment Free Remission

AbstractIn the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.

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Comparison of clinicopathological features and long-term prognosis between mixed predominantly differentiated-type and pure differentiated-type early gastric cancer

BMC Cancer ◽

10.1186/s12885-021-07962-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yutaka Okagawa ◽

Tetsuya Sumiyoshi ◽

Hitoshi Kondo ◽

Yusuke Tomita ◽

Takeshi Uozumi ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Vascular Invasion ◽

Survival Rates ◽

Malignant Potential ◽

Clinicopathological Features ◽

Node Metastasis ◽

Group 5 ◽

Long Term Prognosis

Abstract Background Recent studies have shown that mixed predominantly differentiated-type (MD) early gastric cancer (EGC) might have more malignant potential than pure differentiated-type (PD) EGC. However, no study has analyzed all differentiated-type EGC cases treated endoscopically and surgically. This study aimed to compare the differences in clinicopathological features and long-term prognosis between MD- and PD-EGC. Methods We evaluated all patients with differentiated-type EGCs who were treated endoscopically and surgically in our hospital between January 2010 and October 2014. The clinicopathological features and long-term prognosis of MD-EGC were compared with those of PD-EGC. Results A total of 459 patients with 459 lesions were evaluated in this study; of them, 409 (89.1%) and 50 (10.9%) were classified into the PD and MD groups, respectively. Submucosal invasion was found in 96 (23.5%) patients of the PD group and in 33 (66.0%) patients of the MD group (p < 0.01). The rates of positive lymphatic and vascular invasion and ulceration were significantly higher in the MD group than in the PD group (p < 0.01). The proportion of patients with lymph node metastasis was also significantly higher in the MD group than in the PD group (5 (10%) vs 6 (1.5%), p < 0.01). The 5-year overall and EGC-specific survival rates in the PD group were 88.3 and 99.5%, respectively, while they were 94.0 and 98.0% in the MD group, respectively. Conclusions MD-EGC has more malignant potential than PD-EGC. However, the long-term prognosis of MD-EGC is good and is not significantly different from that of PD-EGC when treated appropriately.

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Robotic and laparoscopic liver surgery for colorectal liver metastases: an experience from a German Academic Center

World Journal of Surgical Oncology ◽

10.1186/s12957-020-02113-1 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Mirhasan Rahimli ◽

Aristotelis Perrakis ◽

Vera Schellerer ◽

Andrew Gumbs ◽

Eric Lorenz ◽

...

Keyword(s):

Abdominal Surgery ◽

Minimally Invasive ◽

Liver Surgery ◽

Colorectal Liver Metastases ◽

Survival Rates ◽

Long Term Outcomes ◽

Short Term ◽

Minimally Invasive Liver Surgery ◽

Previous Abdominal Surgery

Abstract Background Minimally invasive liver surgery (MILS) in the treatment of colorectal liver metastases (CRLM) is increasing in incidence. The aim of this work was to present our experience by reporting short-term and long-term outcomes after MILS for CRLM with comparative analysis of laparoscopic (LLS) and robotic liver surgery (RLS). Methods Twenty-five patients with CRLM, who underwent MILS between May 2012 and March 2020, were selected from our retrospective registry of minimally invasive liver surgery (MD-MILS). Thirteen of these patients underwent LLS and 12 RLS. Short-term and long-term outcomes of both groups were analyzed. Results Operating time was significantly longer in the RLS vs. the LLS group (342.0 vs. 200.0 min; p = 0.004). There was no significant difference between the laparoscopic vs. the robotic group regarding length of postoperative stay (8.8 days), measured blood loss (430.4 ml), intraoperative blood transfusion, overall morbidity (20.0%), and liver surgery related morbidity (4%). The mean BMI was 27.3 (range from 19.2 to 44.8) kg/m2. The 30-day mortality was 0%. R0 resection was achieved in all patients (100.0%) in RLS vs. 10 patients (76.9%) in LLS. Major resections were carried out in 32.0% of the cases, and 84.0% of the patients showed intra-abdominal adhesions due to previous abdominal surgery. In 24.0% of cases, the tumor was bilobar, the maximum number of tumors removed was 9, and the largest tumor was 8.5 cm in diameter. The 1-, 3- and 5-year overall survival rates were 84, 56.9, and 48.7%, respectively. The 1- and 3-year overall recurrence-free survival rates were 49.6 and 36.2%, respectively, without significant differences between RLS vs. LLS. Conclusion Minimally invasive liver surgery for CRLM is safe and feasible. Minimally invasive resection of multiple lesions and large tumors is also possible. RLS may help to achieve higher rates of R0 resections. High BMI, previous abdominal surgery, and bilobar tumors are not a barrier for MILS. Laparoscopic and robotic liver resections for CRLM provide similar long-term results which are comparable to open techniques.

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Clinical long-term and patient-reported outcomes of dental implants in oral cancer patients

International Journal of Implant Dentistry ◽

10.1186/s40729-021-00373-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Eik Schiegnitz ◽

Lena Katharina Müller ◽

Keyvan Sagheb ◽

Lisa Theis ◽

Vahide Cagiran ◽

...

Keyword(s):

Radiation Therapy ◽

Oral Cancer ◽

Cancer Patients ◽

Dental Implants ◽

Survival Rates ◽

Implant Survival ◽

Implant Placement ◽

Patient Reported ◽

Oral Cancer Patients

Abstract Background and purpose The aim of this clinical study was to investigate the clinical long-term and patient-reported outcome of dental implants in patients with oral cancer. In addition, analysis of the influence of radiation therapy, timing of implant insertion, and augmentation procedures on implant survival was performed. Material and methods This retrospective study investigated the clinical outcome of 711 dental implants in 164 oral cancer patients, inserted by experienced surgeons of the Department of Oral and Maxillofacial Surgery, University Medical Center Mainz, Germany. Oral health-related quality of life (OHRQoL) was evaluated. Results Cumulative 5-year and 10-year implant survival rates for all included implants were 87.3% and 80.0%. Implants placed straight after ablative surgery (primary implant placement) and implants placed after completing the oncologic treatment (secondary implant placement) showed a comparable implant survival (92.5% vs. 89.5%; p = 0.635). Irradiation therapy had no significant influence on implant survival of secondary placed implants (p = 0.929). However, regarding implant site (native bone vs. augmented bone) and radiation therapy (non-irradiated bone vs. irradiated bone), implants inserted in irradiated bone that received augmentation procedures showed a statistically significant lower implant survival (p < 0.001). Patients reported a distinct improvement in OHRQoL. Conclusions Promising long-term survival rates of dental implants in patients after treatment of oral cancer were seen. In addition, patients benefit in form of an improved OHRQoL. However, bone augmentation procedures in irradiated bone may result in an impaired implants’ prognosis.

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Surgical treatment of pulmonary artery sarcoma: a report of 17 cases

Pulmonary Circulation ◽

10.1177/2045894020986394 ◽

2021 ◽

Vol 11 (1) ◽

pp. 204589402098639

Author(s):

Wu Song ◽

Long Deng ◽

Jiade Zhu ◽

Shanshan Zheng ◽

Haiping Wang ◽

...

Keyword(s):

Pulmonary Artery ◽

Survival Rates ◽

Tumor Resection ◽

Long Term Results ◽

Pulmonary Endarterectomy ◽

Pulmonary Artery Sarcoma ◽

The Mean ◽

Operative Findings

Pulmonary artery sarcoma (PAS) is a rare and devastating disease. The diagnosis is often delayed, and optimal treatment remains unclear. The aim of this study is to report our experience in the surgical management of this disease. Between 2000 and 2018, 17 patients underwent operations for PAS at our center. The medical records were retrospectively reviewed to evaluate the clinical characteristics, operative findings, the postoperative outcomes, and the long-term results. The mean age at operation was 46.0 ± 12.4 years (range, 26–79 years), and eight (47.1%) patients were male. Six patients underwent tumor resection alone, whereas the other 11 patients received pulmonary endarterectomy (PEA). There were two perioperative deaths. Follow-up was completed for all patients with a mean duration of 23.5 ± 17.6 months (1–52 months). For all 17 patients, the median postoperative survival was 36 months, and estimated cumulative survival rates at 1, 2, 3, and 4 years were 60.0%, 51.4%, 42.9%, and 21.4%, respectively. The mean survival was 37.0 months after PEA and 14.6 months after tumor resection only ( p = 0.046). Patients who had no pulmonary hypertension (PH) postoperatively were associated with improved median survival (48 vs. 5 months, p = 0.023). In conclusion, PAS is often mistaken for chronic pulmonary thromboembolism. The prognosis of this very infrequent disease remains poor. Early detection is essential for prompt and best surgical approach, superior to tumor resection alone, and PEA surgery with PH relieved can provide better chance of survival.

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Short- and Long-Term Outcomes of Robotic Surgery for Rectal Neuroendocrine Tumor

Surgical Innovation ◽

10.1177/15533506211030436 ◽

2021 ◽

pp. 155335062110304

Author(s):

Kentaro Saito ◽

Yusuke Yamaoka ◽

Akio Shiomi ◽

Hiroyasu Kagawa ◽

Hitoshi Hino ◽

...

Keyword(s):

Robotic Surgery ◽

Neuroendocrine Tumor ◽

Surgical Approach ◽

Anal Verge ◽

Survival Rates ◽

Long Term Outcomes ◽

Conversion To Open Surgery ◽

Short And Long Term ◽

Rectal Neuroendocrine Tumor

Background. The optimal radical surgical approach for rectal neuroendocrine tumor (NET) is unknown. Methods. This study evaluated the short- and long-term outcomes of 27 patients who underwent robotic radical surgery for rectal NET between 2011 and 2019. Results. The median distance from the lower border of the tumor to the anal verge was 5.0 cm. The median tumor size was 9.5 mm. Six patients (22%) had lymph node metastasis. The incidences of postoperative complications of grade II and grade III or more according to the Clavien–Dindo classification were 11% and 0%, respectively. All patients underwent sphincter-preserving surgery, and no patients required conversion to open surgery. The median follow-up time was 48.9 months, and both the 3-year overall survival and relapse-free survival rates were 100%. Conclusions. Short- and long-term outcomes of robotic surgery for rectal NET tumor were favorable. Robotic surgery may be a useful surgical approach for rectal NET.

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