855 Treatment strategies, disease recurrence and survival of women with malignant sex cord-stromal cell tumours in Germany

Cellular senescence is a state of stable cell cycle arrest that can be triggered in response to various insults and is characterized by distinct morphological hallmarks, gene expression profiles, and the senescence-associated secretory phenotype (SASP). Importantly, cellular senescence is a key component of normal physiology with tumor suppressive functions. In the last few decades, novel cancer treatment strategies exploiting pro-senescence therapies have attracted considerable interest. Recent insight, however, suggests that therapy-induced senescence (TIS) elicits cell-autonomous and non-cell-autonomous implications that potentially entail detrimental consequences, reflecting the Jekyll and Hyde nature of cancer cell senescence. In essence, the undesirable manifestations that generally culminate in inflammation, cancer stemness, senescence reversal, therapy resistance, and disease recurrence are dictated by the persistent accumulation of senescent cells and the SASP. Thus, mitigating these pro-tumorigenic effects by eliminating these cells or inhibiting their SASP production holds great promise for developing innovative therapeutic strategies. In this review, we describe the fundamental aspects and dynamics of cancer cell senescence and summarize the comprehensive research on the adverse outcomes of TIS. Furthermore, we underline the rationale and motivation of emerging senotherapeutic modalities surrounding the removal of senescent cells and the SASP to help maximize the overall efficacy of cancer therapies.

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Hereditary and acquired complement dysregulation in membranoproliferative glomerulonephritis

Thrombosis and Haemostasis ◽

10.1160/th08-09-0575 ◽

2009 ◽

Vol 101 (02) ◽

pp. 271-278 ◽

Cited By ~ 41

Author(s):

Veronique Fremeaux-Bacchi ◽

Christoph Licht

Keyword(s):

Membranoproliferative Glomerulonephritis ◽

Age Of Onset ◽

Current Knowledge ◽

Treatment Strategies ◽

Specific Treatment ◽

Disease Recurrence ◽

C3 Nephritic Factor ◽

Dense Deposit ◽

Glomerular Deposits ◽

End Stage

SummaryMembranoproliferative glomerulonephritis (MPGN) is a chronic progressive renal disease that is diagnosed on the basis of renal histological features. Several MPGN subtypes have been defined by the localization and composition of glomerular deposits (electron dense, Ig and C3). MPGN II or dense deposit disease (DDD) which is defined by the occurrence of electron dense deposits within the lamina densa of the glomerular basement membrane (GBM) is strongly associated with dysregulation of the alternative complement pathway (AP). However, C3 Nephritic Factor (C3NeF), an autoantibody against the alternative C3 convertase C3bBb, and mutations in regulatory proteins of the AP have also been identified in other subtypes of MPGN and even in glomerulonephritis with mesangial C3 deposits. Clinically, MPGN is characterized by proteinuria (up to nephrotic range) and hypertension, frequent progression to end-stage kidney disease and disease recurrence after renal transplantation. The age of onset varies from childhood to adulthood. In the following we will review our current knowledge of pathogenesis of MPGN and will present a novel classification system of the disease based on pathogenesis rather than on morphology. A better understanding of the pathogenesis of MPGN is crucial for the development of novel, specific treatment strategies.

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Advances in Biomarker-Driven Targeted Therapies in Thyroid Cancer

Cancers ◽

10.3390/cancers13246194 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6194

Author(s):

Prachi Mishra ◽

Dipranjan Laha ◽

Robert Grant ◽

Naris Nilubol

Keyword(s):

Thyroid Cancer ◽

Targeted Therapies ◽

Kinase Inhibitors ◽

Mapk Pathway ◽

Treatment Strategies ◽

Disease Recurrence ◽

Receptor Kinase ◽

New Treatment ◽

Tyrosine Receptor Kinase ◽

Multiple Receptor

Thyroid cancer is the most common type of endocrine malignancy comprising 2–3% of all cancers, with a constant rise in the incidence rate. The standard first-line treatments for thyroid cancer include surgery and radioactive iodine ablation, and a majority of patients show a good response to these therapies. Despite a better response and outcome, approximately twenty percent of patients develop disease recurrence and distant metastasis. With improved knowledge of molecular dysregulation and biological characteristics of thyroid cancer, the development of new treatment strategies comprising novel targets has accelerated. Biomarker-driven targeted therapies have now emerged as a trend for personalized treatments in patients with advanced cancers, and several multiple receptor kinase inhibitors have entered clinical trials (phase I/II/III) to evaluate their safety and efficacy. Most extensively investigated and clinically approved targeted therapies in thyroid cancer include the tyrosine receptor kinase inhibitors that target antiangiogenic markers, BRAF mutation, PI3K/AKT, and MAPK pathway components. In this review, we focus on the current advances in targeted mono- and combination therapies for various types of thyroid cancer.

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Short-changed during the bacillus Calmette–Guérin shortages?

Journal of Clinical Urology ◽

10.1177/2051415820941780 ◽

2020 ◽

pp. 205141582094178

Author(s):

Kenneth R MacKenzie ◽

Sidney D Parker ◽

Dawn Watson ◽

Joanne Cresswell

Keyword(s):

High Risk ◽

Treatment Strategies ◽

Disease Free Survival ◽

Disease Recurrence ◽

Bacillus Calmette Guerin ◽

Level Of Evidence ◽

Significant Difference ◽

Muscle Invasive ◽

Long Term Impact

Objective: Intravesical bacillus Calmette–Guérin (BCG) is the first-line treatment of choice for high-risk non-muscle-invasive bladder cancer (NMIBC). Our aim was to evaluate the long-term impact of BCG shortages on oncological outcomes. Methods: All patients undertaking an initial course of intravesical BCG for intermediate or high risk NMIBC at a single UK cancer centre between August 2012 and August 2014 were evaluated. Compliance was defined as completing 12 doses of BCG within the first year following diagnosis. Results: Due to BCG shortages, 25/114 (22%) patients were compliant with planned maintenance treatment. Compared to the compliant cohort, the non-compliant due to BCG shortages cohort had a higher rate of disease recurrence (35.3% vs. 24%), required more additional intravesical treatments (14.7% vs. 12%) and had a higher rate of radical cystectomy (11.8% vs. 4%). Disease-free survival was superior in the compliant cohort at two years (88% vs. 79.5%) and at 4.5 years (72% vs. 56.1%). There was no statistically significant difference, likely due to the sample size. Conclusions: The consequences of undertreatment due to BCG shortages can impact long-term cancer outcomes. Increased vigilance, robust long-term surveillance and alternative treatment strategies are required for NMIBC patients affected by shortages in BCG supplies. Level of evidence: Level 2b

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Eradication of Measurable Residual Disease in AML: A Challenging Clinical Goal

Cancers ◽

10.3390/cancers13133170 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3170

Author(s):

Paolo Bernasconi ◽

Oscar Borsani

Keyword(s):

Clinical Outcome ◽

Residual Disease ◽

Treatment Strategies ◽

Leukemic Cell ◽

Disease Recurrence ◽

Driver Mutations ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Negative State ◽

Measurable Residual Disease

In non-promyelocytic (non-M3) AML measurable residual disease (MRD) detected by multi-parameter flow cytometry and molecular technologies, which are guided by Consensus-based guidelines and discover very low leukemic cell numbers far below the 5% threshold of morphological assessment, has emerged as the most relevant predictor of clinical outcome. Currently, it is well-established that MRD positivity after standard induction and consolidation chemotherapy, as well as during the period preceding an allogeneic hematopoietic stem cell transplant (allo-HSCT), portends to a significantly inferior relapse-free survival (RFS) and overall survival (OS). In addition, it has become absolutely clear that conversion from an MRD-positive to an MRD-negative state provides a favorable clinical outcome similar to that associated with early MRD negativity. Thus, the complete eradication of MRD, i.e., the clearance of the few leukemic stem cells—which, due to their chemo-radiotherapy resistance, might eventually be responsible of disease recurrence—has become an un-met clinical need in AML. Nowadays, this goal might potentially be achieved thanks to the development of novel innovative treatment strategies, including those targeting driver mutations, apoptosis, methylation patterns and leukemic proteins. The aim of this review is to analyze these strategies and to suggest any potential combination able to induce MRD negativity in the pre- and post-HSCT period.

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Deep learning predicts postsurgical recurrence of hepatocellular carcinoma from digital histopathologic images

Scientific Reports ◽

10.1038/s41598-021-81506-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rikiya Yamashita ◽

Jin Long ◽

Atif Saleem ◽

Daniel L. Rubin ◽

Jeanne Shen

Keyword(s):

Hepatocellular Carcinoma ◽

Deep Learning ◽

Surgical Resection ◽

Treatment Strategies ◽

Recurrence Risk ◽

Disease Recurrence ◽

Risk Scores ◽

Post Surgery ◽

Staging Systems ◽

External Test

AbstractRecurrence risk stratification of patients undergoing primary surgical resection for hepatocellular carcinoma (HCC) is an area of active investigation, and several staging systems have been proposed to optimize treatment strategies. However, as many as 70% of patients still experience tumor recurrence at 5 years post-surgery. We developed and validated a deep learning-based system (HCC-SurvNet) that provides risk scores for disease recurrence after primary resection, directly from hematoxylin and eosin-stained digital whole-slide images of formalin-fixed, paraffin embedded liver resections. Our model achieved concordance indices of 0.724 and 0.683 on the internal and external test cohorts, respectively, exceeding the performance of the standard Tumor-Node-Metastasis classification system. The model’s risk score stratified patients into low- and high-risk subgroups with statistically significant differences in their survival distributions, and was an independent risk factor for post-surgical recurrence in both test cohorts. Our results suggest that deep learning-based models can provide recurrence risk scores which may augment current patient stratification methods and help refine the clinical management of patients undergoing primary surgical resection for HCC.

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Limb-Salvage Surgery of Soft Tissue Sarcoma with Sciatic Nerve Involvement

Sarcoma ◽

10.1155/2018/6483579 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Hussein Sweiti ◽

Noor Tamimi ◽

Fabian Bormann ◽

Markus Divo ◽

Daniela Schulz-Ertner ◽

...

Keyword(s):

Soft Tissue ◽

Sciatic Nerve ◽

Treatment Strategies ◽

Soft Tissue Sarcomas ◽

Oncological Outcome ◽

Type A ◽

Disease Recurrence ◽

Limb Salvage Surgery ◽

Type B ◽

Nerve Involvement

Background. The surgical resection of soft tissue sarcomas (STS) with sciatic nerve involvement presents a significant surgical and oncological challenge. Current treatment strategies pursue a multimodal approach with the aim of limb preservation. We aim to evaluate the outcomes of limb-sparing surgery of STS in a patient cohort and to propose a classification for STS with sciatic nerve involvement. Methods. Patients receiving limb-preserving resections for STS with sciatic nerve involvement between 01/2010 and 01/2017 were included. Clinical and oncological data were prospectively collected in a computerized database and retrospectively analyzed. Sciatic nerve involvement in STS was classified preoperatively as follows: type A for nerve encasement; type B for nerve contact; and type C for no nerve involvement. Results. A total of 364 patients with STS were treated, of which 27 patients had STS with sciatic nerve involvement. Eight patients with type A tumors (29.6%) underwent sciatic nerve resection, and 19 patients with type B tumors (70.4%) received epineural dissections. Disease progression was observed in 8 patients (29.6%) with a local recurrence of 11.1% and distant metastasis in 29.6%. The type of nerve resection significantly influenced leg function but had no impact on disease recurrence or overall survival. Conclusion. In a cohort of carefully selected patients with STS and sciatic nerve involvement, the extent of sciatic nerve resection had no significant impact on disease recurrence or survival. Precise classification of neural involvement may therefore be useful in selecting the appropriate degree of nerve resection, without compromising oncological outcome or unnecessarily sacrificing leg function.

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Transsphenoidal Microsurgery for Growth Hormone-Secreting Pituitary Adenomas: Initial Outcome and Long-Term Results

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.10.5111 ◽

1998 ◽

Vol 83 (10) ◽

pp. 3411-3418 ◽

Cited By ~ 146

Author(s):

Aviva Abosch ◽

J. Blake Tyrrell ◽

Kathleen R. Lamborn ◽

Lisa T. Hannegan ◽

Carol B. Applebury ◽

...

Keyword(s):

Sella Turcica ◽

Treatment Strategies ◽

Disease Recurrence ◽

Mortality Rates ◽

Long Term Results ◽

Long Term Effect ◽

Transsphenoidal Microsurgery ◽

Long Term Follow Up ◽

Cerebrospinal Fluid Leaks

Treatment of acromegaly has long been recognized as necessary to relieve symptoms, halt progression of deformities, and decompress the sella turcica. More recently, treatment strategies have focused on decreasing GH levels to a point at which mortality rates normalize, thereby redefining previous concepts of a cure. No surgical series to date has investigated the long-term effect of treatment on mortality rates. We retrospectively reviewed 254 consecutive patients with acromegaly who underwent transsphenoidal microsurgery of GH-secreting adenomas between 1974–1992. Seventy-six percent of these patients had basal GH levels <5 ng/mL within 30 days of surgery, and 24% had persistent disease. Multivariate analysis revealed that higher stage, grade, and preoperative GH levels were all predictive of persistence (P < 0.01). Long-term follow-up was obtained on 129 of the patients in initial remission. Of these, 9 (7%) had disease recurrence and 120 remained in remission. The incidence of major postoperative complications was 8% (2% permanent diabetes insipidus, 2% cerebrospinal fluid leaks requiring surgery, 2% meningitis, and 2% hypopituitarism), with no mortality. In contrast to the 2.4- to 4.8-fold increased mortality among untreated acromegalics, the mortality rate among patients with posttherapy GH levels <5 ng/mL was equivalent to that of age- and sex-matched controls. Aggressive therapy to normalize GH levels should therefore be instituted at diagnosis.

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Follicular lymphoma: is there an optimal way to define risk?

Hematology ◽

10.1182/hematology.2021000264 ◽

2021 ◽

Vol 2021 (1) ◽

pp. 313-319

Author(s):

Carla Casulo

Keyword(s):

Prognostic Factors ◽

Follicular Lymphoma ◽

Prognostic Markers ◽

Treatment Strategies ◽

Genetic Data ◽

Disease Recurrence ◽

Comprehensive Understanding ◽

Rapid Pace ◽

Patient Prognosis ◽

Clinical Advances

Abstract Follicular lymphoma (FL) has a long natural history and typically indolent behavior. In the present era, there are a plethora of prognostic factors combining clinical, biological, and genetic data to determine patient prognosis and help develop treatment strategies over the course of a patient's lifetime. The rapid pace of tumor-specific and clinical advances in FL has created a challenge in the prioritization and implementation of these factors into clinical practice. Developing a comprehensive understanding of existing prognostic markers in FL will help select optimal ways of utilization in the clinical setting and investigate opportunities to define and intervene upon risk at FL diagnosis and disease recurrence.

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