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1.
Skeletal health in patients with differentiated thyroid carcinoma.
Cellini, M, Rotondi, M, Tanda, ML, Piantanida, E, Chiovato, L, Beck-Peccoz, P, Lania, A, Mazziotti, G
Journal of endocrinological investigation. 2021;(3):431-442
Abstract
Osteoporosis and fractures are important comorbidities in patients with differentiated thyroid cancer (DTC), with potential negative impact on quality of life and survival. The main determinant of skeletal fragility in DTC is the thyrotropin (TSH)-suppressive therapy, which is commonly recommended to prevent disease's recurrence, especially in patients with structural incomplete response after thyroid surgery and radio-iodine therapy. TSH-suppressive therapy can stimulate bone resorption with consequent bone loss, deterioration of bone microstructure and high risk of fragility fractures. The skeletal effects of TSH-suppressive therapy may be amplified when thyroid cancer cells localize to the skeleton inducing alterations in bone remodelling, impairment of bone structure and further increase in risk of fractures. The management of skeletal fragility in DTC may be challenging, since prediction of fractures is a matter of uncertainty and data on effectiveness and safety of bone-active agents in this clinical setting are still scanty. This review deals with pathophysiological, clinical and therapeutic aspects of skeletal fragility of patients with DTC.
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2.
Tumour metabolism and its unique properties in prostate adenocarcinoma.
Bader, DA, McGuire, SE
Nature reviews. Urology. 2020;(4):214-231
Abstract
Anabolic metabolism mediated by aberrant growth factor signalling fuels tumour growth and progression. The first biochemical descriptions of the altered metabolic nature of solid tumours were reported by Otto Warburg almost a century ago. Now, the study of tumour metabolism is being redefined by the development of new molecular tools, tumour modelling systems and precise instrumentation together with important advances in genetics, cell biology and spectroscopy. In contrast to Warburg's original hypothesis, accumulating evidence demonstrates a critical role for mitochondrial metabolism and substantial variation in the way in which different tumours metabolize nutrients to generate biomass. Furthermore, computational and experimental approaches suggest a dominant influence of the tissue-of-origin in shaping the metabolic reprogramming that enables tumour growth. For example, the unique metabolic properties of prostate adenocarcinoma are likely to stem from the distinct metabolism of the prostatic epithelium from which it emerges. Normal prostatic epithelium employs comparatively glycolytic metabolism to sustain physiological citrate secretion, whereas prostate adenocarcinoma consumes citrate to power oxidative phosphorylation and fuel lipogenesis, enabling tumour progression through metabolic reprogramming. Current data suggest that the distinct metabolic aberrations in prostate adenocarcinoma are driven by the androgen receptor, providing opportunities for functional metabolic imaging and novel therapeutic interventions that will be complementary to existing diagnostic and treatment options.
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3.
Treatment of Patients with Advanced Gastroesophageal Adenocarcinoma: Does Age Matter?
Lorenzen, S, Hofheinz, RD
Drugs & aging. 2019;(5):403-409
Abstract
Gastroesophageal cancer is the fourth most frequent malignant disease and, despite significant advances in chemotherapy, the prognosis of unresectable or recurrent gastroesophageal cancer is poor. The majority of patients, nearly two-thirds, are over the age of 65 years at diagnosis. Elderly patients are a heterogeneous population and aging occurs at different rates in different individuals. The chronological age of a patient does not necessarily reflect the physiological age. However, elderly patients are more likely to have a number of concomitant diseases and impaired organ function, which should be considered when making treatment decisions. Therefore, treatment in older adults requires particular caution, and physiologic age rather than chronologic age should be considered when deciding for or against systemic therapy. Older patients are generally underrepresented in clinical trials and many elderly patients do not receive effective combination therapies due to concerns with tolerability. Age itself is not a negative predictive factor and treatment should not be omitted just on the basis of chronological age. Older patients who fulfill the standard inclusion criteria of clinical trials seem to have a similar advantage from palliative chemotherapy for gastroesophageal adenocarcinoma as younger patients; however, large prospective trials in the elderly population are needed to guide clinicians in making evidence-based decisions.
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4.
Advances in the diagnosis and surveillance of Barrett's esophagus (with videos).
, , Trindade, AJ, Navaneethan, U, Aslanian, HR, Bhutani, MS, Krishnan, K, Lichtenstein, DR, Melson, J, Pannala, R, Parsi, MA, et al
Gastrointestinal endoscopy. 2019;(3):325-334
Abstract
BACKGROUND AND AIMS Most patients diagnosed with esophageal adenocarcinoma do not carry a known diagnosis of Barrett's esophagus (BE), suggesting that an improved approach to screening may potentially be of benefit. The use of dysplasia as a biomarker and random biopsy protocols for its detection has limitations. In addition, detecting and appropriately classifying dysplasia in patients with known BE can be difficult. METHODS This document reviews several technologies with a recently established or potential role in the diagnosis and/or surveillance of BE as well as risk stratification for progression to esophageal adenocarcinoma. RESULTS Two technologies were reviewed for imaging or tissue sampling: (1) wide-area transepithelial sampling and (2) volumetric laser endomicroscopy. Four technologies were reviewed for molecular and biomarker technologies for diagnosis and risk stratification: (1) Cytosponge, (2) mutational load, (3) fluorescence in situ hybridization, and (4) immunohistochemistry. CONCLUSION Several technologies discussed in this document may improve dysplasia detection in BE in a wide-field manner. Moreover, the addition of different biomarkers may aid in enhanced risk stratification to optimize approaches to surveillance or treatment for patients with BE.
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5.
The Rationale and Efficacy of Primary and Secondary Prevention in Adenocarcinomas of the Upper Gastrointestinal Tract.
Bornschein, J, Bird-Lieberman, EL, Malfertheiner, P
Digestive diseases (Basel, Switzerland). 2019;(5):381-393
Abstract
While the primary risk factor for oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO) is gastro-oesophageal reflux, the infection with Helicobacter pylori (H. pylori) is the dominant risk factor for gastric cancer. Reduction of reflux by dietary measures and proton pump inhibitors has some merits in OAC prevention, and the chemopreventive effect of Aspirin and statins is being widely investigated; however, improved outcome in OAC occurs primarily as the result of secondary prevention. Early detection of neoplastic lesions in Barrett's metaplasia can be achieved by surveillance endoscopies. Novel endoscopic imaging modalities carry similar importance as the endoscopic treatment techniques as without detection of early lesions, therapy cannot be applied. Minimally invasive approaches are currently being investigated to identify patients with BO who are at particular risk of neoplastic progression. While dietary factors also play an important role in the prevention of gastric cancer and chemoprevention seems to be promising, the most beneficial effect has been shown for the eradication of H. pylori infection, which results in at least a one third reduction of gastric cancer risk. This effect can be further improved if the eradication takes place prior to the development of pre-neoplastic gastric conditions such as mucosal atrophy or intestinal metaplasia (IM). The definition of the "point of no return", after which eradication is less effective, is of high importance, although H. pylori eradication can still be beneficial even at more advance stages of mucosal changes. For this reason, patients with advanced atrophy and IM should undergo endoscopic surveillance in the same way as patients with BO. There is also need for development of non-invasive tests to identify patients at high risk of progression to gastric cancer to improve outcome of these surveillance approaches.
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6.
Risk factors for oesophageal cancer.
Xie, SH, Lagergren, J
Best practice & research. Clinical gastroenterology. 2018;:3-8
Abstract
The two main histological subtypes of oesophageal cancer, squamous cell carcinoma and adenocarcinoma, have distinct risk factor profiles. For oesophageal squamous cell carcinoma, tobacco smoking and excess alcohol use are the main risk factors. For adenocarcinoma, gastro-oesophageal reflux disease and obesity are main risk factors, whereas tobacco smoking is a moderately strong risk factor and infection with Helicobacter pylori decreases the risk. Dietary factors may influence the risk of both types of oesophageal cancer. Genetic factors are involved in the aetiology, but their influence is generally low. The striking male predominance in oesophageal adenocarcinoma is unexplained, although sex hormones may play a role. Risk prediction models combining information on multiple risk factors have shown promising potential in identifying high-risk individuals for targeted prevention and early detection, which should prompt further studies. More high-quality research efforts are warranted for better understanding of the aetiology of oesophageal cancer, particularly in developing countries.
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7.
The role of vitamin D in hepatic metastases from colorectal cancer.
Shaw, E, Massaro, N, Brockton, NT
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2018;(3):259-273
Abstract
Colorectal cancer (CRC) represents a significant health burden worldwide, comprising approximately 10% of annual cancer cases globally. Hepatic metastases are the most common site of CRC metastasis, and are the leading cause of death in CRC patients. There is strong epidemiologic evidence for an inverse association between vitamin D status and risk of CRC; however, the role of vitamin D in the natural history of liver metastases has not yet been investigated. Several researchers have proposed hallmarks of metastases; crucially, metastases can be blocked by interrupting just one rate-limiting step. Vitamin D status has been implicated in each proposed hallmark of metastasis. The aim of this review is to examine the potential role for vitamin D in reducing the development of hepatic metastases from CRC and outline the candidate mechanisms by which vitamin D may mediate these effects. The results of ongoing randomised intervention trials are eagerly awaited to determine whether addressing vitamin D insufficiency in CRC patients could reduce the occurrence of liver metastases, and the consequent morbidity and mortality.
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8.
Irreversible Electroporation in pancreatic ductal adenocarcinoma: Is there a role in conjunction with conventional treatment?
de Liguori Carino, N, O'Reilly, DA, Siriwardena, AK, Valle, JW, Radhakrishna, G, Pihlak, R, McNamara, MG
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018;(10):1486-1493
Abstract
BACKGROUND The incidence of pancreatic ductal adenocarcinoma (PDAC) is rapidly increasing. Up to 30% of patients present with locally advanced disease and therefore are not candidates for surgery. Locally advanced pancreatic cancer (LAPC) is an emerging entity lacking in level III evidence-based recommendations for its treatment. Currently, systemic chemotherapy is the main treatment for LAPC. However, due to lack of response or disease progression, downsizing of the tumour, making it resectable is successful in only a small proportion of patients. Radiotherapy is often advocated to improve local disease control if there is stability following chemotherapy. Recently, Irreversible Electroporation (IRE), a novel non-thermal ablation technique, has been proposed for the treatment of LAPC. AIMS AND METHODS This narrative review aims to explore the potential role and timing for the use of IRE in patients with LAPC. RESULTS To date, there is limited and inconsistent level I and II evidence available in the literature regarding the use of IRE for the treatment of PDAC. DISCUSSION Although some of the preliminary experience of the use of IRE in patients with LAPC is encouraging, it should only be used after conventional evidence-based treatments and/or within the research context.
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9.
Surgical and clinical safety and effectiveness of robot-assisted laparoscopic hysterectomy compared to conventional laparoscopy and laparotomy for cervical cancer: A systematic review and meta-analysis.
Park, DA, Yun, JE, Kim, SW, Lee, SH
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2017;(6):994-1002
Abstract
AIM: This study aimed to evaluate the surgical safety and clinical effectiveness of RH versus LH and laparotomy for cervical cancer. METHODS We searched Ovid-Medline, Ovid-EMBASE, and the Cochrane library through May 2015, and checked references of relevant studies. We selected the comparative studies reported the surgical safety (overall; peri-operative; and post-operative complications; death within 30 days; and specific morbidities), and clinical effectiveness (survival; recurrence; length of stay [LOS]; estimated blood loss [EBL]; operative time [OT]) and patient-reported outcomes. RESULTS Fifteen studies comparing RH with OH and 11 comparing RH with LH were identified. No significant differences were found in survival outcomes. The LOS was shorter and transfusion rate was lower with RH compared to OH or LH. EBL was significantly reduced with RH compared to OH. Compared to OH, overall complications, urinary infection, wound infection, and fever were significantly less frequent with RH. The overall, peri-operative, and post-operative complications were similar in other comparisons. Several patient-reported outcomes were improved with RH, though each outcome was reported in only one study. CONCLUSIONS RH appears to have a positive effect in reducing overall complications, individual adverse events including wound infection, fever, urinary tract infection, transfusion, LOS, EBL, and time to diet than OH for cervical cancer patients. Compared to LH, the current evidence is not enough to clearly determine its clinical safety and effectiveness. Further rigorous prospective studies with long-term follow-up that overcome the many limitations of the current evidence are needed.
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10.
Surgery for pancreatic ductal adenocarcinoma.
Vera, R, Díez, L, Martín Pérez, E, Plaza, JC, Sanjuanbenito, A, Carrato, A
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2017;(11):1303-1311
Abstract
Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement. Prior to surgery preoperative nutritional measures as well as endoscopic biliary drainage can be applied to optimize patient's conditions. Cephalic pancreaticoduodenectomy is the recommended surgical technique in tumors located in the head of the pancreas. The benefits from pyloric preservation, type or reconstruction (one vs. two loops), type of anastomosis (pancreaticojejunostomy vs. pancreaticogastrostomy), intraoperative biopsy of the pancreatic resection margin or the use of intraperitoneal drainages are inconclusive. Total pancreatectomy and/or portal resection should only be performed in particular cases; however, arterial resections have shown no benefits. Radical antegrade modular pancreaticosplenectomy, that can be performed laparoscopically, is the technique used for those tumors located in the pancreatic body-tail.