Longitudinal characterisation of cachexia in patients undergoing surgical resection for cancer

PURPOSE OF REVIEW: The complexity of the cancer cachexia phenotype has undoubtedly hindered researchers' understanding of this devastating syndrome. The presence and magnitude of host-tumour interactions are rarely considered during clinical decision-making within the current staging paradigm. Furthermore, treatment options for those patients who are identified as suffering from cancer cachexia remain extremely limited.RECENT FINDINGS: Previous attempts to characterise cachexia have largely focussed on individual surrogate disease markers, often studied across a limited timeframe. While the adverse prognostic value of clinical and biochemical features is evident, the relationships between these are less clear. Investigation of patients with earlier-stage disease could allow researchers to identify markers of cachexia that precede the refractory stage of the wasting process. Appreciation of the cachectic phenotype within 'curative' populations may aid our understanding of the syndrome's genesis and provide potential routes for prevention, rather than treatment.SUMMARY: Holistic, longitudinal characterisation of cancer cachexia, across all at-risk and affected populations, is of vital importance for future research in the field. This paper presents the protocol for an observational study aiming to create a robust and holistic characterisation of surgical patients with, or at risk of, cancer cachexia.</p

The tip of the iceberg: a giant pelvic atypical lipoma presenting as a sciatic hernia

BACKGROUND: This case report highlights two unusual surgical phenomena: lipoma-like well-differentiated liposarcomas and sciatic hernias. It illustrates the need to be aware that hernias may not always simply contain intra-abdominal viscera. CASE PRESENTATION: A 36 year old woman presented with an expanding, yet reducible, right gluteal mass, indicative of a sciatic hernia. However, magnetic resonance imaging demonstrated a large intra- and extra-pelvic fatty mass traversing the greater sciatic foramen. The tumour was surgically removed through an abdomino-perineal approach. Subsequent pathological examination revealed an atypical lipomatous tumour (synonym: lipoma-like well-differentiated liposarcoma). The patient remains free from recurrence two years following her surgery. CONCLUSION: The presence of a gluteal mass should always suggest the possibility of a sciatic hernia. However, in this case, the hernia consisted of an atypical lipoma spanning the greater sciatic foramen. Although lipoma-like well-differentiated liposarcomas have only a low potential for recurrence, the variable nature of fatty tumours demands that patients require regular clinical and radiological review

Adipose depot gene expression identifies intelectin-1 as potential mediator of the metabolic response to cancer and cachexia

Background Cancer cachexia is a poorly understood metabolic consequence of cancer. During cachexia, different adipose depots demonstrate differential wasting rates. Animal models suggest adipose tissue may be a key driver of muscle wasting through fat–muscle crosstalk, but human studies in this area are lacking. We performed global gene expression profiling of visceral (VAT) and subcutaneous (SAT) adipose from weight stable and cachectic cancer patients and healthy controls. Methods Cachexia was defined as >2% weight loss plus low computed tomography‐muscularity. Biopsies of SAT and VAT were taken from patients undergoing resection for oesophago‐gastric cancer, and healthy controls (n = 16 and 8 respectively). RNA was isolated and reverse transcribed. cDNA was hybridised to the Affymetrix Clariom S microarray and data analysed using R/Bioconductor. Differential expression of genes was assessed using empirical Bayes and moderated‐t‐statistic approaches. Category enrichment analysis was used with a tissue‐specific background to examine the biological context of differentially expressed genes. Selected differentially regulated genes were validated by qPCR. Enzyme‐linked immunosorbent assay (ELISA) for intelectin‐1 was performed on all VAT samples. The previously‐described cohort plus 12 additional patients from each group also had plasma I = intelectin‐1 ELISA carried out. Results In VAT vs. SAT comparisons, there were 2101, 1722, and 1659 significantly regulated genes in the cachectic, weight stable, and control groups, respectively. There were 2200 significantly regulated genes from VAT in cachectic patients compared with controls. Genes involving inflammation were enriched in cancer and control VAT vs. SAT, although different genes contributed to enrichment in each group. Energy metabolism, fat browning (e.g. uncoupling protein 1), and adipogenesis genes were down‐regulated in cancer VAT (P = 0.043, P = 5.4 × 10−6 and P = 1 × 10−6 respectively). The gene showing the largest difference in expression was ITLN1, the gene that encodes for intelectin‐1 (false discovery rate‐corrected P = 0.0001), a novel adipocytokine associated with weight loss in other contexts. Conclusions SAT and VAT have unique gene expression signatures in cancer and cachexia. VAT is metabolically active in cancer, and intelectin‐1 may be a target for therapeutic manipulation. VAT may play a fundamental role in cachexia, but the down‐regulation of energy metabolism genes implies a limited role for fat browning in cachectic patients, in contrast to pre‐clinical models

Review of remote monitoring systems for the delivery of sustainable and resilient water infrastructure

Purpose This paper aims to present a literature review of remote monitoring systems for water infrastructure in the Global South. Design/methodology/approach Following initial scoping searches, further examination was made of key remote monitoring technologies for water infrastructure in the Global South. A standard literature search methodology was adopted to examine these monitoring technologies and their respective deployments. This hierarchical approach prioritised “peer-reviewed” articles, followed by “scholarly” publications, then “credible” information sources and, finally, “other” relevant materials. The first two search phases were conducted using academic search services (e.g. Scopus and Google Scholar). In the third and fourth phases, Web searches were carried out on various stakeholders, including manufacturers, governmental agencies and non-governmental organisations/charities associated with Water, Sanitation and Hygiene (WASH) in the Global South. Findings This exercise expands the number of monitoring technologies considered in comparison to earlier review publications. Similarly, preceding reviews have largely focused upon monitoring applications in sub-Saharan Africa (SSA). This paper explores opportunities in other geographical regions and highlights India as a significant potential market for these tools. Research limitations/implications This review predominantly focuses upon information/data currently available in the public domain. Practical implications Remote monitoring technologies enable the rapid detection of broken water pumps. Broken water infrastructure significantly impacts many vulnerable communities, often leading to the use of less protected water sources and increased exposure to water-related diseases. Further to these public health impacts, there are additional economic disadvantages for these user communities. Originality/value This literature review has sought to address some key technological omissions and to widen the geographical scope associated with previous investigations

Endoscopic ultrasound in the assessment of advanced duodenal adenomatosis in familial adenomatous polyposis

Objective Current surveillance strategies for duodenal adenomatosis in familial adenomatous polyposis (FAP) miss malignancies and underestimate cancer risk in ampullary disease. This study aimed to evaluate the utility of endoscopic ultrasound (EUS) in the assessment of FAP patients with duodenal and/or ampullary polyposis referred for surgical intervention. Design A retrospective analysis of FAP patients undergoing index EUS between December 2006 and May 2015 was performed. Follow-up was completed in January 2018, including review of all EUS procedures and surgical interventions (median follow-up 6 years). Results Fifty-five patients underwent 188 EUS procedures. Six patients (11%) developed malignancy (three duodenal, three ampullary). Ampullary cancer risk was underestimated by Spigelman stage and overestimated by Kashiwagi classification. Ultrasound findings were poor predictors of malignancy, with common bile duct dilatation being the only finding present in one EUS prior to a diagnosis of ampullary cancer. The best predictors of ampullary malignancy were an ampullary polyp size >3 cm and an increase >1 cm in ampullary polyp size. Ampullary polyp size >3 cm provided the best predictive value, correctly identifying two of the three cases of ampullary cancer and both patients with high-grade dysplasia. EUS biopsy failed to detect malignancy later confirmed by surgical histology in two patients. Conclusion EUS surveillance confers little additional benefit to standard endoscopic surveillance in FAP patients. The best predictor of ampullary malignancy is an ampullary polyp >3 cm; this could be regarded as a relative indication for surgery

Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients

Background&nbsp; In order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients.&nbsp; Methods&nbsp; One hundred seven patients (15 weight-stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight-loss of UGIC patients was 8.1 (9.3\%). Cachexia was defined as weight-loss &ge;5\%. Rectus&thinsp;abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real-time&ndash;polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n&thinsp;=&thinsp;52), forkhead box O transcription factors (n&thinsp;=&thinsp;59), ubiquitin E3 ligases (n&thinsp;=&thinsp;59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n&thinsp;=&thinsp;59, as markers of autophagy), myosin heavy-chain (MyHC, n&thinsp;=&thinsp;54), dystrophin (n&thinsp;=&thinsp;39), &beta;-dystroglycan (n&thinsp;=&thinsp;52), and &beta;-sarcoglycan (n&thinsp;=&thinsp;52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255&thinsp;days (range 581&ndash;1955&thinsp;days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non-cachectic cancer patients; and (iii) cancer patients surviving &le;1 vs. {\textgreater}1&thinsp;year post operatively.&nbsp; Results&nbsp; Cancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P&thinsp;=&thinsp;0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P&thinsp;=&thinsp;0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P&thinsp;=&thinsp;0.024]. &beta;-Dystroglycan levels were higher in cachectic compared with non-cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P&thinsp;=&thinsp;0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326&thinsp;days, P&thinsp;=&thinsp;0.023) and dystrophin levels (median 341 vs. 660&thinsp;days, P&thinsp;=&thinsp;0.008).&nbsp; Conclusions&nbsp; The present study has identified intramuscular protein level of &beta;-dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers

Endoscopic ultrasound in the assessment of advanced duodenal adenomatosis in familial adenomatous polyposis

Objective: Current surveillance strategies for duodenal adenomatosis in familial adenomatous polyposis (FAP) miss malignancies and underestimate cancer risk in ampullary disease. This study aimed to evaluate the utility of endoscopic ultrasound (EUS) in the assessment of FAP patients with duodenal and/or ampullary polyposis referred for surgical intervention. Design: A retrospective analysis of FAP patients undergoing index EUS between December 2006 and May 2015 was performed. Follow-up was completed in January 2018, including review of all EUS procedures and surgical interventions (median follow-up 6 years). Results: Fifty-five patients underwent 188 EUS procedures. Six patients (11%) developed malignancy (three duodenal, three ampullary). Ampullary cancer risk was underestimated by Spigelman stage and overestimated by Kashiwagi classification. Ultrasound findings were poor predictors of malignancy, with common bile duct dilatation being the only finding present in one EUS prior to a diagnosis of ampullary cancer. The best predictors of ampullary malignancy were an ampullary polyp size >3 cm and an increase >1 cm in ampullary polyp size. Ampullary polyp size >3 cm provided the best predictive value, correctly identifying two of the three cases of ampullary cancer and both patients with high-grade dysplasia. EUS biopsy failed to detect malignancy later confirmed by surgical histology in two patients. Conclusion: EUS surveillance confers little additional benefit to standard endoscopic surveillance in FAP patients. The best predictor of ampullary malignancy is an ampullary polyp >3 cm; this could be regarded as a relative indication for surgery