Publications by authors named "David Chan"

481 Publications

Epigenetic Silencing of miR-33b Promotes Peritoneal Metastases of Ovarian Cancer by Modulating the TAK1/FASN/CPT1A/NF-κB Axis.

Cancers (Basel) 2021 Sep 24;13(19). Epub 2021 Sep 24.

Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Peritoneal metastases are frequently found in high-grade serous carcinoma (HGSOC) patients and are commonly associated with a poor prognosis. The tumor microenvironment (TME) is a complex milieu that plays a critical role in epigenetic alterations driving tumor development and metastatic progression. However, the impact of epigenetic alterations on metastatic ovarian cancer cells in the harsh peritoneal microenvironment remains incompletely understood. Here, we identified that miR-33b is frequently silenced by promoter hypermethylation in HGSOC cells derived from metastatic omental tumor tissues. Enforced expression of miR-33b abrogates the oncogenic properties of ovarian cancer cells cocultured in omental conditioned medium (OCM), which mimics the ascites microenvironment, and in vivo tumor growth. Of note, restoration of miR-33b inhibited OCM-upregulated de novo lipogenesis and fatty acid β-oxidation in ovarian cancer cells, indicating that miR-33b may play a novel tumor suppressor role in the lipid-mediated oncogenic properties of metastatic ovarian cancer cells found in the omentum. Mechanistic studies demonstrated that miR-33b directly targets transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing the activities of fatty acid synthase (FASN) and carnitine palmitoyltransferase 1A (CPT1A) in modulating lipid metabolic activities and simultaneously inhibiting the phosphorylation of NF-κB signaling to govern the oncogenic behaviors of ovarian cancer cells. Thus, our data suggest that a lipid-rich microenvironment may cause epigenetic silencing of miR-33b, which negatively modulates ovarian cancer peritoneal metastases, at least in part, by suppressing TAK1/FASN/CPT1A/NF-κB signaling.
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http://dx.doi.org/10.3390/cancers13194795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508465PMC
September 2021

Activity of the Gamma Secretase Inhibitor AL101 in Desmoid Tumors: A Case Report of 2 Adult Cases.

Curr Oncol 2021 Sep 21;28(5):3659-3667. Epub 2021 Sep 21.

Department of Medical Oncology, Peter MacCallum Cancer Centre Royal Melbourne Hospital, Melbourne, VIC 3000, Australia.

Desmoid tumors (aggressive fibromatosis) are soft tissue mesenchymal tumors that can be locally invasive and life-threatening. Depending on the location, these tumors are often unresectable or tend to recur after surgery. To date, there are no approved systemic therapies for desmoid tumors. These tumors typically harbor mutations in the β-catenin oncogene or the tumor suppressor gene adenomatous polyposis coli, resulting in constitutive activation of the WNT pathway. The Notch pathway is part of the underlying cause for desmoid tumor development, possibly due to crosstalk with the WNT pathway, providing a rationale for Notch inhibition as a therapeutic strategy. The gamma secretase activation of the Notch receptor can be targeted with investigational gamma secretase inhibitors. In this case report, we follow the course of 2 patients with desmoid tumors treated with the highly potent, parenterally administered investigational gamma secretase inhibitor AL101, resulting in long-lasting responses. Case 1 reports on a patient with a mesenteric desmoid tumor who participated in a phase 1 trial and then transitioned into a compassionate use program; Case 2 reports on a patient with recurrent pelvic tumors receiving AL101 through a compassionate use program. After tumor progression on other systemic therapies, Cases 1 and 2 had confirmed partial responses (41% and 60% maximal tumor size decrease from baseline) recorded after 1.0 and 1.6 years of treatment with AL101, with a duration of response of 8.6+ and 2.6+ years, respectively. Also, in a phase 1 study of AL102, a potent orally administered gamma secretase inhibitor that shares structural features with AL101, a patient with a desmoid tumor was noted to have tumor shrinkage. Formal clinical testing of AL102 for the treatment of patients with desmoid tumors that are not amenable to surgery or are refractory to/recurrent from other prior therapies is currently underway.
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http://dx.doi.org/10.3390/curroncol28050312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482204PMC
September 2021

The Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment.

Cancers (Basel) 2021 Sep 12;13(18). Epub 2021 Sep 12.

Shenzhen Institute of Research and Innovation (HKU-SIRI), The University of Hong Kong, Shenzhen 518057, China.

Emerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as a hypoxia-inducible gene for promoting tumor progression in ovarian cancer peritoneal metastases. We demonstrated that BCL2A1 was induced not only by hypoxia but also other physiological stresses through NF-κB signaling and then was gradually reduced by the ubiquitin-proteasome pathway in ascites-derived ovarian cancer cells. The upregulated BCL2A1 was frequently found in advanced metastatic ovarian cancer cells, suggesting its clinical relevance in ovarian cancer metastatic progression. Functionally, BCL2A1 enhanced the foci formation ability of ovarian cancer cells in a stress-conditioned medium, colony formation in an ex vivo omental tumor model, and tumor dissemination in vivo. Under stress conditions, BCL2A1 accumulated and colocalized with mitochondria to suppress intrinsic cell apoptosis by interacting with the BH3-only subfamily BCL2 members HRK/BAD/BID in ovarian cancer cells. These findings indicate that BCL2A1 is an early response factor that maintains the survival of ovarian cancer cells in the harsh tumor microenvironment.
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http://dx.doi.org/10.3390/cancers13184577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469659PMC
September 2021

Genioplasty and Mandibular Implants.

Facial Plast Surg 2021 Sep 16. Epub 2021 Sep 16.

Otolaryngology and Facial Plastic Associates, Fort Worth, Texas.

Genioplasty is a useful technique employed for both aesthetic and, in the case of obstructive sleep apnea, functional purposes. Mandibular implants similarly represent a powerful tool in the facial surgeons armamentarium. Herein, we review relevant anatomy, patient evaluation, and various techniques employing both alloplastic augmentation and osseous modification of the mandible.
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http://dx.doi.org/10.1055/s-0041-1735307DOI Listing
September 2021

Systematic review and meta-analysis of the influence of prophylactic pyloric balloon dilatation in the prevention of early delayed gastric emptying after oesophagectomy.

Dis Esophagus 2021 Sep 2. Epub 2021 Sep 2.

Department of Upper GI Surgery, Derriford Hospital, Plymouth, UK.

Background: Early delayed gastric emptying (DGE) occurs in up to 50% of patients following oesophagectomy, which can contribute to increased anastomotic leak and respiratory infection rates. Although the treatment of DGE in the form of pyloric balloon dilatation (PBD) post-operatively is well established, there is no consensus on the optimal approach in the prevention of DGE. The aim of this review was to determine the efficacy of prophylactic PBD in the prevention of DGE following oesophagectomy.

Method: PubMed, MEDLINE and the Cochrane Library (January 1990 to April 2021) were searched for studies reporting the outcomes of prophylactic PBD in patients who underwent oesophagectomy. The primary outcome measure was the rate of DGE. Secondary outcome measures include anastomotic leak rate and length of hospital stay.

Results: Three studies with a total of 203 patients [mean age 63 (26-82) years, 162 males (79.8%)] were analyzed. PBD with a 20-mm balloon was performed in 165 patients (46 patients had PBD and botox therapy) compared with 38 patients who had either no intervention or botox alone (14 patients). The pooled rates of early DGE [16.27%, 95% CI (12.29-20.24) vs. 39.02% (38.87-39.17) (P < 0.001)] and anastomotic leak [8.55%, 95% CI (8.51-8.59) vs. 12.23% (12.16-12.31), P < 0.001] were significantly lower in the PBD group.

Conclusion: Prophylactic PBD with a 20-mm balloon significantly reduced the rates of early delayed gastric emptying and anastomotic leak following oesophagectomy.
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http://dx.doi.org/10.1093/dote/doab062DOI Listing
September 2021

Feasibility and Utility of Mobile Applications for the Evaluation of Urology Residents' Surgical Competence.

Urology 2021 Aug 24. Epub 2021 Aug 24.

Smith Institute for Urology at Northwell Health of the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY.

Objective: To provide real-time assessment and feedback on the competency of urology residents' surgical skill via mobile applications and examine their feasibility and utility.

Materials And Methods: Two mobile application-based systems (SIMPL and myTIPreport) were sequentially implemented for the case-by-case assessment of residents' performance of surgical skills at a single institution. Data was collected regarding residents' perception of their feedback pre- and post-implementation of the applications. Faculty were surveyed after their implementation to determine their feasibility and utility.

Results: 297 individual evaluations were completed with SIMPL and 822 with myTIPreport over four and eleven months respectively. Post-implementation, residents showed significantly improved perceptions regarding the quantity and personalization of surgical skill feedback (P = .043 and .005 respectively). A majority (75%) of the faculty found the mobile applications feasible to use, an improvement compared to prior methods of resident evaluation, and would recommend continued use.

Conclusion: This study represents the first documented use of real-time surgical competency assessment in urology. The use of mobile applications to evaluate urology residents' surgical competency in clinical practice is both feasible and useful. Their use may allow for more individualized surgical skill teaching during training and for the verification of the surgical skills necessary to practice autonomously.
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http://dx.doi.org/10.1016/j.urology.2021.05.112DOI Listing
August 2021

The quality of clinical trials in neuroendocrine tumours; have we learnt from our mistakes? An evaluation of phase II and phase III clinical trials.

J Neuroendocrinol 2021 Sep 16;33(9):e13015. Epub 2021 Aug 16.

The University of Sydney, Camperdown, NSW, Australia.

The quality and reporting of neuroendocrine tumour (NET) clinical trials has previously been found to be heterogeneous impairing trial interpretability. We aimed to perform an updated review of the quality of phase II/III clinical trials in NET to assess if trial design and reporting have improved since 2011. We performed a PubMed search for phase II/III trials evaluating systemic anticancer therapies or liver-directed therapies published between 2011 and 2018. Data collected comprised administrative data, study population characteristics, endpoints, reporting and statistical design parameters, and results. Sixty studies were included (5218 patients): 50 phase II and 10 phase III trials. Study populations were heterogeneous: 52% of trials allowed tumours from various primary sites, 28% allowed both well- and poorly-differentiated tumour morphology or did not specify, and 57% did not report proliferative indices and/or tumour grade in ≥80% of the study population. Only 36% of trials mandated radiological disease progression on participant enrolment using a validated measure. Statistical design and primary endpoint were clearly defined in 67% and 88% of trials, respectively. Toxicity (88%), radiological response rate (85%) and progression-free survival/time to progression (82%) were well reported in a majority of trials, but health-related quality of life was included in the minority. Of the randomised trials (n = 11), study populations were more homogeneous and study design was more often clearly defined; however, only 45% mandated radiological progression at baseline as measured per Response Evaluation Criteria In Solid Tumours, and reporting of health-related quality of life (55%) remained suboptimal. The design and reporting of NET clinical trials, predominantly of single-arm phase II trials, remains suboptimal and has not considerably improved over time despite the growth in our knowledge of the biology and unique characteristics of NETs. Higher quality is seen in randomised trials, although certain design and reporting elements remain inadequate in some studies. We must prioritise the design and conduct of NET clinical trials to effectively inform future research and guide practice change.
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http://dx.doi.org/10.1111/jne.13015DOI Listing
September 2021

Trajectory of Pain, Functional Limitation, and Parental Coping Resources Following Pediatric Short-stay Surgery: Factors Impacting Rate of Recovery.

Clin J Pain 2021 09;37(9):698-706

Department of Pain, Sydney Children's Hospital, Randwick.

Objectives: Although there are many benefits of short-stay hospital admissions for high volume, pediatric surgical procedures, this model of care places greater responsibility on parents for the management of children's pain. This study aimed to document the trajectory of child pain outcomes and a range of parent-reported functional outcomes following discharge from a short-stay surgical admission. Moreover, we aimed to document the trajectory of parental perceived personal coping resources. Second, we assessed whether parental dispositional factors, assessed before hospital discharge, predicted the child's pain intensity and parent-reported functional recovery.

Methods: Participants included children (aged 4 to 14 y) admitted for a short-stay tonsillectomy or appendectomy, and their parents. Parents completed a questionnaire before discharge from hospital. Demographic and surgical information was recorded from medical records. Following discharge, daily assessments of pain and functioning were carried out over a 10-day period using iPods or mobile phones. Predischarge and postdischarge data were obtained for 55 child and parent dyads.

Results: Pain intensity scores returned to low levels (2/10 or less) by day 5 for appendectomy and day 10 for tonsillectomy. Parents' perceived personal coping resources increased more slowly following tonsillectomy than appendectomy. Controlling for time since surgery and parental coping resources, parental pain-related catastrophizing was a significant predictor of child pain and functional recovery.

Discussion: Short-stay surgery results in parents facing considerable burden in managing their child's pain and functional impairment over a 10-day period. The potential value of screening for parental pain-related catastrophizing before discharge from hospital warrants further consideration and may enable identification of children likely to experience poorer recovery.
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http://dx.doi.org/10.1097/AJP.0000000000000966DOI Listing
September 2021

Fis1 ablation in the male germline disrupts mitochondrial morphology and mitophagy, and arrests spermatid maturation.

Development 2021 08 12;148(16). Epub 2021 Aug 12.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena CA 91125, USA.

Male germline development involves choreographed changes to mitochondrial number, morphology and organization. Mitochondrial reorganization during spermatogenesis was recently shown to require mitochondrial fusion and fission. Mitophagy, the autophagic degradation of mitochondria, is another mechanism for controlling mitochondrial number and physiology, but its role during spermatogenesis is largely unknown. During post-meiotic spermatid development, restructuring of the mitochondrial network results in packing of mitochondria into a tight array in the sperm midpiece to fuel motility. Here, we show that disruption of mouse Fis1 in the male germline results in early spermatid arrest that is associated with increased mitochondrial content. Mutant spermatids coalesce into multinucleated giant cells that accumulate mitochondria of aberrant ultrastructure and numerous mitophagic and autophagic intermediates, suggesting a defect in mitophagy. We conclude that Fis1 regulates mitochondrial morphology and turnover to promote spermatid maturation.
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http://dx.doi.org/10.1242/dev.199686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380467PMC
August 2021

Correction to: Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers.

Clin Epigenetics 2021 Aug 3;13(1):151. Epub 2021 Aug 3.

Department of Obstetrics and Gynaecology, L747 Laboratory Block, LKS Faculty of Medicine, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, People's Republic of China.

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http://dx.doi.org/10.1186/s13148-021-01141-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330114PMC
August 2021

Temozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review.

Oncologist 2021 Aug 3. Epub 2021 Aug 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

Background: Grade 3 gastroenteropancreatic neuroendocrine neoplasms (G3 GEPNENs) are often aggressive, and the optimal treatment is unclear for this subgroup of neuroendocrine neoplasms (NENs). Temozolomide (TEM)-based regimens have been increasingly used to treat grade 1-2 NENs, but their efficacy in G3 NENs remains undetermined. We aimed to assess the clinical efficacy of TEM-containing regimens in advanced grade 3 GEPNENs.

Materials And Methods: A multicenter retrospective review (2008-2018) of patients with metastatic/unresectable G3 GEPNENs who received a TEM-containing regimen was undertaken within a North American partnership to pool data. The primary endpoint was time to treatment failure (TTF). Radiologic response was extracted from local reports.

Results: One hundred and thirty patients in six high-volume NEN centers were included (median age 55, 64% male, 18% functional, 67% pancreatic NEN). Forty-nine percent were well-differentiated, 35% poorly differentiated, and 15% unknown based on local pathology reports. The regimen used was capecitabine and temozolomide (CAPTEM) in 92% and TEM alone in 8%. Radiological response by local assessment was seen in 36% of patients. Median TTF was 3.6 months and median overall survival (OS) 19.2 months. Six percent of patients required discontinuation of therapy due to adverse events. TTF was longer in first-line treatment (7.8 months vs. 2.9 months; hazard ratio, 1.62; 95% confidence interval, 1.11-2.36; p = .015) and in patients with pancreatic NENs (panNENs) compared with gastrointestinal NENs (5.8 months vs 1.8 months; p = .04). The overall response rate was higher in the first-line setting (51% vs 29%; p = .02) and in panNEN (41% vs 23%; p = .04).

Conclusion: This is the largest TEM treatment series in G3 NEN, involving collaboration of several major North American NEN centers as a partnership. Thirty-six percent of patients showed some degree of radiographic response, and treatment was generally well tolerated, although the median duration of response was short. Response rates and time to treatment failure were superior in the first-line setting. CAPTEM should be considered a viable treatment option in this setting. Further randomized trials are warranted.

Implications For Practice: Neuroendocrine neoplasms (NENs) are heterogeneous, and optimal treatment for aggressive grade 3 (G3) NENs remains undetermined. The capecitabine and temozolomide (CAPTEM) regimen has been used in low-grade pancreas NENs but there are few data for its safety and efficacy in the G3 setting. This article reports on the efficacy of temozolomide-containing regimens, particularly CAPTEM, in management of G3 NENs. The good tolerance and response rate show that CAPTEM should be considered a viable regimen in treatment of G3 NENs pending confirmatory prospective studies.
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http://dx.doi.org/10.1002/onco.13923DOI Listing
August 2021

Nuclear HKII-P-p53 (Ser15) Interaction is a Prognostic Biomarker for Chemoresponsiveness and Glycolytic Regulation in Epithelial Ovarian Cancer.

Cancers (Basel) 2021 Jul 7;13(14). Epub 2021 Jul 7.

Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, Centre for Infection, Immunity and Inflammation, Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

In epithelial ovarian cancer (EOC), carboplatin/cisplatin-induced chemoresistance is a major hurdle to successful treatment. Aerobic glycolysis is a common characteristic of cancer. However, the role of glycolytic metabolism in chemoresistance and its impact on clinical outcomes in EOC are not clear. Here, we show a functional interaction between the key glycolytic enzyme hexokinase II (HKII) and activated P-p53 (Ser15) in the regulation of bioenergetics and chemosensitivity. Using translational approaches with proximity ligation assessment in cancer cells and human EOC tumor sections, we showed that nuclear HKII-P-p53 (Ser15) interaction is increased after chemotherapy, and functions as a determinant of chemoresponsiveness as a prognostic biomarker. We also demonstrated that p53 is required for the intracellular nuclear HKII trafficking in the control of glycolysis in EOC, associated with chemosensitivity. Mechanistically, cisplatin-induced P-p53 (Ser15) recruits HKII and apoptosis-inducing factor (AIF) in chemosensitive EOC cells, enabling their translocation from the mitochondria to the nucleus, eliciting AIF-induced apoptosis. Conversely, in p53-defective chemoresistant EOC cells, HKII and AIF are strongly bound in the mitochondria and, therefore, apoptosis is suppressed. Collectively, our findings implicate nuclear HKII-P-p53(Ser15) interaction in chemosensitivity and could provide an effective clinical strategy as a promising biomarker during platinum-based therapy.
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http://dx.doi.org/10.3390/cancers13143399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306240PMC
July 2021

Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers.

Clin Epigenetics 2021 Jul 22;13(1):142. Epub 2021 Jul 22.

Department of Obstetrics and Gynaecology, L747 Laboratory Block, LKS Faculty of Medicine, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, People's Republic of China.

Background: In contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC.

Methods: An epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells.

Results: Global DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells.

Conclusions: This study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment.
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http://dx.doi.org/10.1186/s13148-021-01130-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296615PMC
July 2021

The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression.

Int J Mol Sci 2021 Jun 18;22(12). Epub 2021 Jun 18.

Department of Obstetrics & Gynaecology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China.

Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's "Seed and Soil" hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.
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http://dx.doi.org/10.3390/ijms22126560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235734PMC
June 2021

Marked improvement in hyperammonaemic encephalopathy from multimodal treatment of metastatic neuroendocrine tumour.

BMJ Case Rep 2021 Jun 30;14(6). Epub 2021 Jun 30.

Medical Oncology, Royal North Shore Hospital, University of Sydney, Royal North Shore Hospital, New South Wales, Australia.

Gastroenteropancreatic neuroendocrine tumours (GEPNETs) are a heterogenous group of tumours which are rising in incidence. Morbidity and mortality related to these tumours is dependent on the location of metastatic spread. Hyperammonaemia and subsequent encephalopathy has previously been described in GEPNET and is typically associated with a poor prognosis. We describe a case of a 55-year-old woman with hyperammonaemic encephalopathy and a new diagnosis of GEPNET. Given the poor prognosis and the outcomes in this patient group we feel this case highlights the benefit of a multimodality treatment approach including peptide receptor radionucleotide therapy and transarterial chemoembolisation.
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http://dx.doi.org/10.1136/bcr-2020-241191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246280PMC
June 2021

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer.

Front Cell Dev Biol 2021 28;9:673295. Epub 2021 May 28.

Faculty of Medical Laboratory Science, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2's correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.
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http://dx.doi.org/10.3389/fcell.2021.673295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194078PMC
May 2021

Kidney Biopsy in Patients With Monoclonal Gammopathy: A Multicenter Retrospective Cohort Study.

Front Med (Lausanne) 2021 24;8:687149. Epub 2021 May 24.

State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Guangdong Provincial Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, China.

To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury. This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy. We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding ( = 34, 33.7%), followed by membranous nephropathy ( = 18, 17.8%) and membranoproliferative nephritis ( = 8, 7.9%). Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury. Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS).
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http://dx.doi.org/10.3389/fmed.2021.687149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180861PMC
May 2021

High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME).

J Clin Med 2021 May 17;10(10). Epub 2021 May 17.

Laboratory of Cardiac Imaging and 3D Printing, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China.

Left ventricular hypertrophy (LVH) caused by cardiac variant Fabry disease (FD) is typically late-onset and may mimic LVH caused by abnormal loading conditions. We aimed to determine the prevalence of FD in a non-selective patient population of everyday practice presenting with LVH, including those with hypertension and valve disease. We measured plasma alpha-galactosidase A activity using dried blood spot tests in 499 (age = 66 ± 13 years; 336 men) Hong Kong Chinese patients with LVH defined as maximal LV septal/posterior wall thickness ≥13 mm on echocardiography. Patients with low enzyme activity underwent mutation analysis of the GLA gene. Eight (age = 53-74 years; all men) unrelated patients (1.6%) had low plasma alpha-galactosidase A activity (0.57 ± 0.27 μmol/L wb/hr) and all were confirmed to have the GLA IVS4 + 919G > A mutation. FD patients presented with heart failure ( = 5), heart block ( = 2), ventricular tachycardia ( = 1), chest pain ( = 3), and/or murmur ( = 1). Uncontrolled hypertension ( = 4) and/or severe mitral/aortic valve pathology ( = 2) were frequent. Ethnic subgroups included Teochew ( = 5), Canton ( = 2), and Wenzhou ( = 1). Endomyocardial biopsy ( = 6) revealed hypertrophic myocytes with vacuolization and dense lamellar bodies. Late-onset IVS4 + 919G > A FD is prevalent among Chinese LVH patients, and should be considered as a cause of LVH in adult patients even when hypertension and/or valve pathology are present.
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http://dx.doi.org/10.3390/jcm10102160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157141PMC
May 2021

The Cavovarus Ankle: Approaches to Ankle Instability and Inframalleolar Deformity.

Clin Podiatr Med Surg 2021 Jul;38(3):461-481

East Liverpool City Hospital, East Liverpool, OH, USA.

Pathologic affects from a cavus foot deformity range from flexible subtle to rigid severe deformities and are related to many pathologic conditions of the foot and ankle. Understanding the underlying deformity and the deforming force is essential in treating the cavus ankle and foot. Every deformity is different and unique to a given patient; therefore, surgical plans should be modified to each patient.
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http://dx.doi.org/10.1016/j.cpm.2020.12.015DOI Listing
July 2021

CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer.

Front Immunol 2021 7;12:667177. Epub 2021 May 7.

Faculty of Medical Laboratory Science, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Accumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8 T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.
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http://dx.doi.org/10.3389/fimmu.2021.667177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138166PMC
May 2021

A pilot study of everolimus and radiation for neuroendocrine liver metastases.

Endocr Relat Cancer 2021 Jun 21;28(8):541-548. Epub 2021 Jun 21.

Division of Medical Oncology, University of Toronto, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

Liver metastases are common in patients with neuroendocrine tumours. For patients, management must balance disease control with consideration of toxicity, given limited treatment options. Everolimus has demonstrated effectiveness in neuroendocrine neoplasms. Given emerging data of a synergistic effect with radiation therapy, we evaluated combined everolimus and radiation for neuroendocrine liver metastases. This single-arm, single-centre prospective pilot study evaluated the safety and efficacy of combined everolimus and radiotherapy for well-differentiated neuroendocrine liver metastases. Patients with unresectable liver metastases received everolimus for 30 days, followed by concurrent everolimus and liver radiotherapy, then a further 14 days of everolimus. Tolerability was evaluated using the CTCAE v.4.03. Individual metastasis response rate and local control were measured by RECIST v1.1. Overall survival, progression-free survival and freedom from a change in systemic therapy were estimated by the Kaplan-Meier method. Forty metastases were treated in 14 patients. No grade 3 or higher toxicities were identified in the concurrent treatment phase; one patient developed grade 3 toxicity in the post-radiation phase. Overall response rate was 38%. One- and 2-year local control were 97% and 71%. Median progression-free survival was 12 months. One- and 2-year overall survival were 100% and 92%. In conclusion, combined everolimus and radiation are well-tolerated for neuroendocrine liver metastases and are associated with excellent local control. The approach of selective local ablation of oligometastatic or oligoprogressive disease warrants further evaluation in this patient population.
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http://dx.doi.org/10.1530/ERC-21-0030DOI Listing
June 2021

Computed tomography (CT)-defined sarcopenia and myosteatosis are prevalent in patients with neuroendocrine neoplasms (NENs) treated with peptide receptor radionuclide therapy (PRRT).

Eur J Clin Nutr 2021 May 13. Epub 2021 May 13.

Cancer Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Background/objectives: Neuroendocrine neoplasms (NEN) may predispose patients to malnutrition. CT-defined sarcopenia and myosteatosis are common in other tumour types and recognized adverse prognostic factors. However, the prevalence and prognostic impact of sarcopenia and myosteatosis remain undetermined in NEN patients to date.

Methods: A retrospective study of NEN patients treated with peptide receptor radionuclide therapy (PRRT) at a tertiary institution from 2012 to 2017. Patients with PET/CT imaging at baseline and follow-up were included. The L3 slice of the co-localizing CT was analysed using the Alberta Protocol. Skeletal muscle cross-sectional area and muscle attenuation were measured and compared with pre-defined cut-offs. The primary endpoint was the prevalence of sarcopenia and myosteatosis according to previously published cut-offs.

Results: Fourty-nine patients (median age 64 (range 26-80) years) were included. The most common primary sites of tumour were the small bowel (51%) and pancreas (26%). Baseline sarcopenia was prevalent in 67% of patients and myosteatosis in 71%. Forty-five percent of patients gained weight over the course of PRRT. The presence of baseline sarcopenia was not associated with progression-free survival (20.8 mo vs. 20.7 mo, HR 0.86, p = 0.70) nor overall survival. Similarly, baseline myosteatosis (PFS 19.5 mo vs. 20.8 mo, HR 0.77, p = 0.47) was not significantly associated with survival outcomes. The mean (SD) age of those with myosteatosis was 60.8 ± 11.6 years compared to 49.7 ± 12.7 years for those without (p = 0.003).

Conclusions: Body composition analysis is feasible using routinely acquired PET/CT data for patients with NEN. CT-defined sarcopenia and myosteatosis are prevalent in NEN patients, although myosteatosis is more common with increasing age. These findings were not associated with worsened overall or progression-free survival in the current study.
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http://dx.doi.org/10.1038/s41430-021-00915-4DOI Listing
May 2021

Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy.

Eur J Surg Oncol 2021 Oct 30;47(10):2543-2550. Epub 2021 Apr 30.

Sydney Medical School, The University of Sydney, Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, NSW, Australia.

Background: Pancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection.

Materials And Methods: Prospectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed.

Results: Between 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010).

Conclusion: Patients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.
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http://dx.doi.org/10.1016/j.ejso.2021.04.005DOI Listing
October 2021

Th17 Cells Provide Mucosal Protection against Gastric Trypanosoma cruzi Infection.

Infect Immun 2021 06 16;89(7):e0073820. Epub 2021 Jun 16.

Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri, USA.

Trypanosoma cruzi is the intracellular parasite of Chagas disease, a chronic condition characterized by cardiac and gastrointestinal morbidity. Protective immunity requires CD4 T cells, and Th1 cells and gamma interferon (IFN-γ) are important players in host defense. More recently, Th17 cells and interleukin 17A (IL-17A) have been shown to exert protective functions in systemic T. cruzi infection. However, it remains unclear whether Th17 cells and IL-17A protect in the mucosa, the initial site of parasite invasion in many human cases. We found that IL-17RA knockout (KO) mice are highly susceptible to orogastric infection, indicating an important function for this cytokine in mucosal immunity to T. cruzi. To investigate the specific role of Th17 cells for mucosal immunity, we reconstituted RAG1 KO mice with T. cruzispecific T cell receptor transgenic Th17 cells prior to orogastric T. cruzi challenges. We found that Th17 cells provided protection against gastric mucosal T. cruzi infection, indicated by significantly lower stomach parasite burdens. macrophage infection assays revealed that protection by Th17 cells is reduced with IL-17A neutralization or reversed by loss of macrophage NADPH oxidase activity. Consistently with this, mice lacking functional NADPH oxidase were not protected by Th17 cell transfer. These data are the first report that Th17 cells protect against mucosal T. cruzi infection and identify a novel protective mechanism involving the induction of NADPH oxidase activity by IL-17A. These studies provide important insights for Chagas vaccine development and, more broadly, increase our understanding of the diverse roles of Th17 cells in host defense.
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http://dx.doi.org/10.1128/IAI.00738-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208511PMC
June 2021

PARP (Poly ADP-Ribose Polymerase) inhibitors for locally advanced or metastatic breast cancer.

Cochrane Database Syst Rev 2021 Apr 22;4:CD011395. Epub 2021 Apr 22.

NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Australia.

Background: Locally advanced and metastatic breast cancer remains a challenge to treat. With emerging study results, it is important to interpret the available clinical data and apply the evidence offering the most effective treatment to the right patient. Poly(ADP Ribose) Polymerase (PARP) inhibitors are a new class of drug and their role in the treatment of locally advanced and metastatic breast cancer is being established.

Objectives: To determine the efficacy, safety profile, and potential harms of Poly(ADP-Ribose) Polymerase (PARP) inhibitors in the treatment of patients with locally advanced or metastatic breast cancer. The primary outcome of interest was overall survival; secondary outcomes included progression-free survival, tumour response rate, quality of life, and adverse events.

Search Methods: On 8 June 2020, we searched the Cochrane Breast Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via OvidSP, Embase via OvidSP, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal and ClinicalTrials.gov. We also searched proceedings from the major oncology conferences as well as scanned reference lists from eligible publications and contacted corresponding authors of trials for further information, where needed.

Selection Criteria: We included randomised controlled trials on participants with locally advanced or metastatic breast cancer comparing 1) chemotherapy in combination with PARP inhibitors, compared to the same chemotherapy without PARP inhibitors or 2) treatment with PARP inhibitors, compared to treatment with other chemotherapy. We included studies that reported on our primary outcome of overall survival and secondary outcomes including progression-free survival, tumour response rate, quality of life, and adverse events.

Data Collection And Analysis: We used standard methodological procedures defined by Cochrane. Summary statistics for the endpoints used hazard ratios (HR) with 95% confidence intervals (CI) for overall survival and progression-free survival, and odds ratios (OR) for response rate (RR) and toxicity.

Main Results: We identified 49 articles for qualitative synthesis, describing five randomised controlled trials that were included in the quantitative synthesis (meta-analysis). A sixth trial was assessed as eligible but had ended prematurely and no data were available for inclusion in our meta-analysis. Risk of bias was predominately low to unclear across all studies except in regards to performance bias (3/5 high risk) and detection bias for the outcomes of quality of life (2/2 high risk) and reporting of adverse events (3/5 high risk). High-certainty evidence shows there may be a small advantage in overall survival (HR 0.87, 95% CI 0.76 to 1.00; 4 studies; 1435 patients). High-certainty evidence shows that PARP inhibitors offer an improvement in PFS in locally advanced/metastatic HER2-negative, BRCA germline mutated breast cancer patients (HR 0.63, 95% CI 0.56 to 0.71; 5 studies; 1474 patients). There was no statistical heterogeneity for these outcomes. Subgroup analyses for PFS outcomes based on trial level data were performed for triple-negative breast cancer, hormone-positive and/or HER2-positive breast cancer, BRCA1 and BRCA2 germline mutations, and patients who had received prior chemotherapy for advanced breast cancer or not. The subgroup analyses showed a persistent PFS benefit regardless of the subgroup chosen. Pooled analysis shows PARP inhibitors likely result in a moderate improvement in tumour response rate compared to other treatment arms (66.9% vs 48.9%; RR 1.39, 95% CI 1.24 to 1.54; 5 studies; 1185 participants; moderate-certainty evidence). The most common adverse events reported across all five studies included neutropenia, anaemia and fatigue. Grade 3 or higher adverse events probably occur no less frequently in patients receiving PARP inhibitors (59.4% for PARP arm versus 64.5% for non-PARP arm, RR 0.98, 95% CI 0.91 to 1.04; 5 studies; 1443 participants; moderate-certainty evidence). Only two studies reported quality of life outcomes so this was not amenable to meta-analysis. However, both studies that did assess quality of life showed PARP inhibitors were superior compared to physician's choice of chemotherapy in terms of participant-reported outcomes.

Authors' Conclusions: In people with locally advanced or metastatic HER2-negative, BRCA germline mutated breast cancer, PARP inhibitors offer an improvement in progression-free survival, and likely improve overall survival and tumour response rates. This systematic review provides evidence supporting the use of PARP inhibitors as part of the therapeutic strategy for breast cancer patients in this subgroup. The toxicity profile for PARP inhibitors is probably no worse than chemotherapy but more information is required regarding quality of life outcomes, highlighting the importance of collecting such data in future studies. Future studies should also be powered to detect clinically important differences in overall survival and could focus on the role of PARP inhibitors in other relevant breast cancer populations, including HER2-positive, BRCA-negative/homologous recombination repair-deficient and Programmed Death-Ligand 1 (PDL1) positive.
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http://dx.doi.org/10.1002/14651858.CD011395.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092476PMC
April 2021

Vigilance for carcinoid heart disease is still required in the era of somatostatin analogues: Lessons from a case series.

Asia Pac J Clin Oncol 2021 Apr 14. Epub 2021 Apr 14.

Department of Endocrine Oncology, University Hospital, Uppsala, Sweden.

Aim: Carcinoid heart disease (CHD) is a well-documented complication of neuroendocrine tumors (NETs) due to secreted hormones causing fibrosis. Somatostatin analogues (SSAs) can decrease hormonal secretion and inhibit tumor growth. The reported incidence of CHD has decreased as SSA use has increased. We describe a series of patients who have developed CHD even though they were treated with SSA therapy.

Methods: Nine patients were seen in four centers in Australia and New Zealand. The average duration of follow-up from diagnosis was 39 months.

Results: Three patients had Grade 1 and six Grade 2 disease by World Health Organization 2010 criteria. All patients had no CHD symptoms at baseline and started SSA therapy soon after diagnosis, yet developed significant, symptomatic cardiac dysfunction in their disease course. The median time from NET diagnosis to SSA initiation was 1 month, and median time from NET diagnosis to CHD diagnosis was 23 months (range 4-52). All patients who were tested had persistently increased hormonal levels (chromogranin A, urinary 5-hydroxyindolacetic acid).

Conclusions: The good symptomatic control afforded by SSAs should not lead to reduced vigilance in screening for CHD, especially in patients with persistently elevated hormonal assays. Clinicians should consider regular echocardiographic screening in patients with a secretory syndrome.
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http://dx.doi.org/10.1111/ajco.13577DOI Listing
April 2021

Real-world management and patient perspectives on QOL with neuroendocrine tumors: An ANZ perspective.

Asia Pac J Clin Oncol 2021 Apr;17 Suppl 2:3-10

NeuroEndocrine Cancer Australia, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1111/ajco.13587DOI Listing
April 2021

Percutaneous transcystic removal of gallbladder and common bile duct stones: a narrative review.

Acta Radiol 2021 Apr 12:2841851211006915. Epub 2021 Apr 12.

Department of Upper GI Surgery, 6634University Hospitals Plymouth NHS Trust, Plymouth, UK.

The incidence of gallstone-related complications is rising, thus leading to increases in waiting list times for elective laparoscopic cholecystectomy (LC). Percutaneous cholecystostomy (PC) provides immediate biliary drainage and may be used as an emergency option in a critically unwell patient as a bridge to surgery, or as the management option of a patient who is not fit for surgery. However, a significant number of these patients may be readmitted after PC with recurrent acute cholecystitis or pancreatitis, leading to significant morbidity and mortality. The aim of the present review was to analyze the available literature surrounding the use of the transcystic approach, including the extraction and balloon expulsion method, in the management of patients with gallbladder stones and/or common bile duct (CBD) stones. The full text of 18 articles were reviewed, of which four were included in this review. Results showed an overall success rate of CBD stone extraction in 118 of 139 patients (84.9%), gallbladder stone extraction in 97 of 114 (85.0%), and CBD stone expulsion in 27 of 29 (93.1%). Percutaneous CBD and gallbladder stone extraction may be a safe management option for elderly or co-morbid patients who are not appropriate for surgical intervention. However, the evidence base surrounding this is very limited; therefore, further research is required in order to evaluate this in more detail.
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http://dx.doi.org/10.1177/02841851211006915DOI Listing
April 2021
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