Right vs. Left colorectal cancer - Where do we draw the line?

PURPOSE: No consensus on the definition of right and left colorectal cancer (CRC) exists, nor studies offering histological or molecular basis for such categorisation. This study investigated the regional variations in the histological and molecular characteristics of CRCs, with the objective of determining an optimal division point between right and left CRCs. MATERIALS AND METHODS: An observational study of consecutive patients who underwent CRC resection (1995-2022) at Concord Hospital, Sydney was performed. Clinicopathological data were extracted from a prospective database and seven permutations of right-left divisions considered. Logistic regression tested association between the right-left divisions and pathological characteristics. Receiver operating characteristic and area under the curve (AUC) analyses determined the discriminative ability of each division to predict 18 pathology characteristics. RESULTS: 3753 patients underwent a CRC resection (2120 male; mean 69.5yrs [SD12.6]). There was regional variation in tumours with respect to tumour infiltrating lymphocytes (TILs), mismatch repair deficiency (dMMR), and mutant BRAF (mBRAF). Left-sided tumours were less likely to demonstrate TILs (P < 0.001), be dMMR (P < 0.001), and express mBRAF (P < 0.001). Division at the descending-sigmoid junction yielded highest discriminative abilities: TILs - AUC 0.66, dMMR - AUC 0.76, and mBRAF - AUC 0.73. CONCLUSION: This is the first study to provide a pathological basis on which right- and left-sided cancers may be defined, and found the optimal division point between the right and left colorectum to be at the descending-sigmoid junction. Further research is needed to determine whether this can facilitate individualised patient management.

Tissue morphometric measurements do not predict survival following colorectal cancer surgery.

BACKGROUND: Ex vivo tissue morphometric (TM) measurements have been proposed as a quality marker for colorectal cancer (CRC) surgery. However, their survival associations require clarification. This study aimed to evaluate the feasibility of capturing TM measurements based on ex vivo fresh specimen images and explore the association between these TM measurements and survival outcomes. METHODS: A prospective cohort study at Concord Hospital, Sydney was conducted with Stage I to III CRC patients (2009-2019) who underwent an anterior resection (AR) or right hemicolectomy (RH). Using high-resolution digital photographs of fresh CRC specimens, ex vivo tissue morphometric (TM) measurements-resected mesentery area (TM A), distances from high vascular tie to tumour (TM B) and bowel wall (TM C), and bowel length (TM D)-were recorded using Image J. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. Linear regression models tested association between TM measurements and lymph node (LN) yield. RESULTS: Of the 1,425 patients who underwent CRC surgery, TM measurements were performed on 312 patients, with an average age of 69.4 years (SD 12.3), of whom 52.9% were male. The majority had an AR (57.8%). Among AR patients, a 5-year OS rate of 77.4% and a DFS rate of 70.1% were observed, with TM measurements bearing no relationship to survival outcomes. Similarly, RH patients exhibited a 5-year OS rate of 67.2% and a DFS rate of 63.1%, with TM measurements again showing no association with survival. Only TM D (P = 0.02) measurements were associated with the number of LNs examined. CONCLUSION: This study successfully demonstrates the feasibility of measuring TM measurements on photographs of ex vivo fresh specimens following CRC surgery. The lack of association with survival outcomes questions the utility of TM measurements as a quality metric of CRC surgery.

A Novel Use of Embryonic Gut Organoid Culture to Investigate Duodenal Atresia.

BACKGROUND: The cause of duodenal atresia (DA) is not known. Tandler's "solid cord" hypothesis conflicts with current biological evidence. In humans, a genetic aetiology is supported by the association with Trisomy 21. Interruption of Fgf10 is the strongest genetic link to DA in mice, demonstrating an increased incidence and severity as embryos mature. This project aimed to develop an organoid model to facilitate ex vivo DA research on the FGF10/FGFR2b signalling pathway. We hypothesised that DA morphology represents an evolving spectrum of disease and that Fgf10 knockout organoids would vary in growth pattern compared to wild-type. METHODS: Organoids were cultured from the duodenum of E12.5 Fgf10 knockout, heterozygous and wild-type embryos, using an air-liquid interface with Growth Factor reduced Matrigel. Organoids were photographed every 48 h to observe growth. Organoids were isolated and fixed after 14 days, then stained with DAPI, KI-67, and cytokeratin to demonstrate proliferation and differentiation. RESULTS: Wild-type duodenum developed into crypt-forming organoids. Fgf10 heterozygous duodenum failed to progress beyond the development stage of spheroids. Fgf10 knockout duodenum failed to demonstrate any growth. Wholemount staining showed the greatest cell proliferation and differentiation in wild-type tissue. CONCLUSION: This research presents a novel concept for the growth of embryonic gastrointestinal tissue to inform normal biology. The small sample numbers and restricted culture duration limit longer-term growth analysis. While this model serves as a potential ex vivo setting for future research, that research should consider organoid models with greater standardisation and other gastrointestinal regions. LEVEL OF EVIDENCE: Animal/laboratory study.

Low anterior resection syndrome phenotypes-Different symptom profiles for different patients.

AIM: Attention is increasingly being turned to functional outcomes as being central to colorectal cancer (CRC) survivorship. The current literature may underestimate the impact of evacuatory dysfunction on patient satisfaction with bowel function after anterior resection (AR) for CRC. The aim of this study was to investigate the impact of post-AR symptoms of storage and evacuatory dysfunction on patient satisfaction and health-related quality of life (HRQoL). METHOD: A cross-sectional study was performed at an Australian hospital of patients post-AR for CRC (2012-2021). The postoperative bowel function scores used were: low anterior resection syndrome (LARS), St Mark's incontinence, Cleveland Clinic constipation and Altomare obstructive defaecation syndrome scores. Eight 'storage' and 'evacuatory' dysfunction symptoms were derived. A seven-point Likert scale measured patient satisfaction. The SF36v2® measured HRQoL. Linear regression assessed the association between symptoms, patient satisfaction and HRQoL. RESULTS: Overall, 248 patients participated (mean age 70.8 years, 57.3% male), comprising 103 with rectal cancer and 145 with sigmoid cancer. Of the symptoms that had a negative impact on patient satisfaction, six reflected evacuatory dysfunction, namely excessive straining (p < 0.001), one or more unsuccessful bowel movement attempt(s)/24 h (p < 0.001), anal/vaginal digitation (p = 0.005), regular enema use (p = 0.004), toilet revisiting (p = 0.004) and >10 min toileting (p = 0.004), and four reflected storage dysfunction, namely leaking flatus (p = 0.002), faecal urgency (p = 0.005), use of antidiarrhoeal medication (p = 0.001) and incontinence-related lifestyle alterations (p < 0.001). A total of 130 patients (53.5%) had 'no LARS', 56 (23.1%) had 'minor LARS' and 57 (23.4%) had 'major LARS'. Fifty-seven (44.5%) patients classified as having 'no LARS' had evacuatory dysfunction. CONCLUSION: Postoperative storage and evacuatory dysfunction symptoms have an adverse impact on patient satisfaction and HRQoL post-AR. The importance of comprehensively documenting symptoms of evacuatory dysfunction is highlighted. Further research is required to develop a patient satisfaction-weighted LARS-specific HRQoL instrument.

The association between KRAS and histopathological growth patterns and the impact on resection margins around vasculature and bile ducts in colorectal liver metastases.

The liver is the most frequent and often the only site of distant disease in colorectal cancer and, of all treatment protocols currently in use, resection is the most likely to result in long-term cure. Within the liver, tumour proximity to major vasculature and biliary structures poses a resection challenge, requiring a balance of achieving negative margins while preserving adequate vascular circulation and biliary drainage. The focus on parenchymal sparing resections are important but just as important may be the 'biological' behaviour of the tumour. In colorectal liver metastases (CRLM), biomarkers such as the Kirsten rat sarcoma oncogene homologue (KRAS) gene and histological growth patterns (HGPs) further improve the prognostication after resection. However, to date, the association between the KRAS status and HGPs in CRLM and their impact on resection margins around major vasculature or biliary structures in terms of overall survival and recurrence rates are unclear. The aim of this review was to explore the available evidence for the association between KRAS and HGPs in CRLM and attempt to define their impact on resection margins near major structures.

Complete mesocolic excision for colon cancer: current status and controversies.

According to Hohenberger's original description, complete mesocolic excision for colon cancer involves precise dissection of the avascular embryonic plane between the parietal retroperitoneum and visceral peritoneum of the mesocolon. This ensures mesocolic integrity, access to high ligation of the supplying vessels at their origin and an associated extended lymphadenectomy. Results from centres which have adopted this approach routinely have demonstrated that oncological outcomes can be improved by the rigorous implementation of established principles of cancer surgery. Meticulous anatomical dissection along embryonic planes is a well-established principle of precision cancer surgery used routinely by the specialist colorectal surgeon. Therefore, the real question concerns the need for true central vascular ligation and associated extended (D3) lymphadenectomy or otherwise, particularly along the superior mesenteric vessels when performing a right colectomy. Whether this approach results in improved overall or disease-free survival remains unclear and its role remains controversial particularly given the potential for significant morbidity associated with a more extensive central vascular dissection. Current literature is limited by considerable bias, as well as inconsistent and variable terminology, and the results of established randomized trials are awaited. As a result of the current state of equipoise, various national guidelines have disparate recommendations as to when complete mesocolic excision should be performed if at all. This article aims to review the rationale for and technical aspects of complete mesocolic excision, summarize available short and long term outcome data and address current controversies.

Local Heat Dissipation and Elasticity of Suspended Silicon Nanowires Revealed by Dual Scanning Electron and Thermal Microscopies.

A novel combined setup, with a scanning thermal microscope (SThM) embedded in a scanning electron microscope (SEM), is used to characterize a suspended silicon rough nanowire (NW), which is epitaxially clamped at both sides and therefore monolithically integrated in a microfabricated device. The rough nature of the NW surface, which prohibits vacuum-SThM due to loose contact for heat dissipation, is circumvented by decorating the NW with periodic platinum dots. Reproducible approaches over these dots, enabled by the live feedback image provided by the SEM, yield a strong improvement in thermal contact resistance and a higher accuracy in its estimation. The results-thermal resistance at the tip-sample contact of 188±3.7K µW-1 and thermal conductivity of the NW of 13.7±1.6W m-1 K-1-are obtained by performing a series of approach curves on the dots. Noteworthy, the technique allows measuring elastic properties at the same time-the moment of inertia of the NW is found to be (6.1±1.0) × 10-30m4-which permits to correlate the respective effects of the rough shell on heat dissipation and on the NW stiffness. The work highlights the capabilities of the dual SThM/SEM instrument, in particular the interest of systematic approach curves with well-positioned and monitored tip motion.

The use of adjuvant chemotherapy is not associated with recurrence or cancer-specific death following curative resection for stage III rectal cancer: a competing risks analysis.

BACKGROUND: The role of adjuvant chemotherapy (AC) in stage III rectal cancer (RC) has been argued based on evidence from its use in colon cancer. Previous trials have analysed disease-free and overall survivals as endpoints, rather than disease recurrence. This study compares the competing risks incidences of recurrence and cancer-specific death between patients who did and did not receive AC for stage III RC. METHODS: Consecutive patients who underwent a potentially curative resection for stage III RC (1995-2019) at Concord Hospital, Sydney, Australia, were studied. AC was considered following multidisciplinary discussion. Primary outcome measures were the competing risks incidences of disease recurrence and cancer-specific death. Associations between these outcomes and use of AC (and other variables) were tested by regression modelling. RESULTS: Some 338 patients (213 male, mean age 64.4 years [SD12.7]) were included. Of these, 208 received AC. The use of AC was associated with resection year (adjusted OR [aOR] 1.74, 95%CI 1.27-2.38); age ≥75 years (aOR0.04, 95%CI 0.02-0.12); peripheral vascular disease (aOR0.08, 95%CI 0.01-0.74); and postoperative abdomino-pelvic abscess (aOR0.23, 95%CI 0.07-0.81). One hundred fifty-seven patients (46.5%) were diagnosed with recurrence; death due to RC occurred in 119 (35.2%). After adjustment for the competing risk of non-cancer death, neither recurrence nor RC-specific death was associated with AC (HR0.97, 95%CI 0.70-1.33 and HR0.72, 95%CI 0.50-1.03, respectively). CONCLUSION: This study found no significant difference in either recurrence or cancer-specific death between patients who did and did not receive AC following curative resection for stage III RC.

Splenic flexure cancer survival: a 25-year experience and implications for complete mesocolic excision (CME) and central vascular ligation (CVL).

BACKGROUND: The management of splenic flexure cancers (SFCs) in the era of complete mesocolic excision (CME) and central vascular ligation (CVL) is challenging because of its variable lymphatic drainage. This study aimed to compare survival outcomes for SFCs and non-SFCs, and better understand the clinicopathological characteristics which may define a distinct SFC phenotype. METHODS: An observational cohort study at Concord Hospital, Sydney was conducted with patients who underwent resection for colon adenocarcinoma (1995-2019). Clinicopathological data were extracted from a prospective database. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. RESULTS: Of 2149 patients with colon cancer, 129 (6%) had an SFC. The overall 5-year OS and DFS rates were 63.6% (95% CI 62.5-64.7) and 59.4% (95% CI 58.3-60.5), respectively. SFCs were not associated with OS (P = 0.6) or DFS (P = 0.5). SFCs were more likely to present urgently (P < 0.001) with obstruction (P < 0.001) or perforation (P = 0.03), and more likely to require an open operation (P < 0.001). These characteristics were associated with poorer survival outcomes. No differences were noted between SFCs and non-SFCs with respect to tumour stage (P = 0.3). CONCLUSION: SFCs have a distinct phenotype, the individual characteristics of which are associated with poorer survival. However, the survivals of SFCs and non-SFCs are similar, possibly because the most important determinant of outcome, tumour stage, is no different between the groups. This may have implications for the surgical approach to SFCs with respect to standardization of CME and CVL surgery for these cancers.

Right hemicolectomy anastomotic leak study: a review of right hemicolectomy in the binational clinical outcomes registry (BCOR).

BACKGROUNDS: Surgery remains mainstay management for colon cancer. Post-operative anastomotic leak (AL) carries significant morbidity and mortality. Rates of, and risk factors associated with AL following right hemicolectomy remain poorly documented across Australia and New Zealand. This study examines the Bowel Cancer Outcomes Registry (BCOR) to address this. METHODS: A retrospective cohort study was undertaken of consecutive BCOR-registered right hemicolectomy patients undergoing resection for colon cancer (2007-2021). The primary outcome measure was AL incidence. Clinicopathological data were extracted from the BCOR. Factors associated with AL and primary anastomosis were identified using logistic regression. AL-rate trends were assessed by linear regression. RESULTS: Of 13 512 patients who had a right hemicolectomy (45.2% male, mean age 72.5 years, SD 12.1), 258 (2.0%) had an AL. On multivariate analysis, male sex (OR 1.33; 95% CI 1.03-1.71) and emergency surgery (OR 1.41; 95% CI 1.04-1.92) were associated with AL. Private health insurance status (OR 0.66; 95% CI 0.50-0.88) and minimally-invasive surgery (OR 0.61; 95% CI 0.47-0.79) were protective for AL. Anastomotic technique (handsewn versus stapled) was not associated with AL (P = 0.84). Patients with higher ASA status (OR 0.47; 95% CI 0.39-0.58), advanced tumour stage (OR 0.56; 95% CI 0.50-0.63), and emergency surgery (OR 0.16; 95% CI 0.13-0.20) were less likely to have a primary anastomosis. AL-rate and year of surgery showed no association (P = 0.521). CONCLUSION: The AL rate in Australia and New Zealand following right hemicolectomy is consistent with the published literature and was stable throughout the study period. Sex, emergency surgery, insurance status, and minimally invasive surgery are associated with AL incidence.

Predicting strength outcomes for upper limb nerve transfer surgery in tetraplegia.

We report a retrospective study of 112 nerve transfers in 39 participants to investigate predictors of strength outcomes after nerve transfer surgery for upper limb reanimation in tetraplegia. We measured clinical and pre- and intraoperative neurophysiological assessment variables and compared them with strength outcomes 2 years after nerve transfer surgery. We found statistically significant improvement in Medical Research Council strength grades after nerve transfer surgery with lower cervical spine injuries (between one and two grades), lower donor nerve stimulation thresholds (half of a grade), greater motor evoked potential activity in recipient nerves (half of a grade) and greater muscle responses to intraoperative stimulation of donor (half of a grade) and recipient nerves (half of a grade).Level of evidence: III.

Spine abnormalities associated with bone edema on sacroiliac joints MRI in patients with non-inflammatory chronic back pain.

OBJECTIVE: To investigate whether bone marrow edema (BME) fulfilling the ASAS definition of magnetic resonance imaging (MRI) sacroiliitis is associated with non-inflammatory spine abnormalities in patients with definite mechanical chronic back pain (CBP). METHODS: Patients with definite mechanical CBP, according to the physician, started before the age of 45 and be lasting for more than 3months but less than 3years underwent a protocolized MRI and radiographs of sacroiliac joint (SIJ) and spine. BME and structural changes were scored, by three readers, for SIJ as well as non-inflammatory abnormalities for spine, including degenerative lesions and static disorders. Univariate analysis by Chi2 test was performed to search a statistical association between BME fulfilling the ASAS definition of MRI sacroiliitis and the presence of at least one non-inflammatory spine abnormality. RESULTS: A total of 94 patients were analyzed, 27 (29%) patients had BME and 16 (17%) patients had BME fulfilling the ASAS definition of MRI sacroiliitis; 86 (91.5%) patients had at least one non-inflammatory spine abnormality which are associated into 3 distinct clusters. BME was slightly more frequent at the lower and posterior part of the SIJ. MRI sacroiliitis was associated with interspinous bursitis, facet joint effusion and lateral spinal deviation and was more likely in patients with at least one non-inflammatory spine abnormality (OR: 4.96, 95% CI [1.47; 16.72]). CONCLUSIONS: BME fulfilling the ASAS definition of MRI sacroiliitis is significantly associated with non-inflammatory spine abnormalities in patients with mechanical CBP.

The association between tumour sub-site and local nodal and/or distant metastasis at the time of resection of colorectal cancer: a prospective study of 3,360 consecutive cases.

The concept that right and left sided colorectal cancer may be biologically different has led to a review of the pathology and molecular characteristics expressed by the two sides. The aim of this cross-sectional study was to examine the association between tumour sub-sites and the presence of any metastasis by multivariable modelling. Pathology data were drawn from a hospital series of 3360 consecutive patients who had their first cancer resected between 1995 and 2019 inclusive. A preliminary analysis of the distribution of sex, age and a range of routinely reported pathology features showed that the simple division of the bowel into right and left sides masks the considerable variation in pathology features which occurs between sub-sites within each side. Logistic regression adjusting for sex, age, a range of routinely reported pathology features and tumour sub-site showed that age ≤70, direct tumour spread (T3 and T4), high grade, venous invasion and perineural invasion all carried a significantly increased risk for the presence of metastatic spread. The only tumour sub-sites to show an increased risk were the sigmoid colon and rectum (adjusted odds ratio 1.72, P < 0.001 and 1.78, P < 0.001, respectively). These findings suggest that multivariable modelling could usefully be applied to identify associations between sub-sites and molecular characteristics.

Apical Node Involvement Does Not Influence Prognosis After Potentially Curative Resection for Stage III Colorectal Cancer: A Competing Risks Analysis.

OBJECTIVE: To examine the independent prognostic value of ALN status in patients with stage III CRC. SUMMARY OF BACKGROUND DATA: Early CRC staging classified nodal involvement by level of involved nodes in the operative specimen, including both locoregional and apical node status, in contrast to the American Joint Committee on Cancer/tumor nodes metastasis (TNM) system where tumors are classified by the number of nodes involved. Whether ALN status has independent prognostic value remains controversial. METHODS: Consecutive patients who underwent curative resection for Stage III CRC from 1995 to 2012 at Concord Hospital, Sydney, Australia were studied. ALN status was classified as: (i) ALN absent, (ii) ALN present but not histologically involved, (iii) ALN present and involved. Outcomes were the competing risks incidence of CRC recurrence and CRC-specific death. Associations between these outcomes and ALN status were compared with TNM N status results. RESULTS: In 706 patients, 69 (9.8%) had an involved ALN, 398 (56.4%) had an uninvolved ALN and 239 (33.9%) had no ALN identified. ALN status was not associated with tumor recurrence [adjusted hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.84-1.26] or CRC-specific death (HR 1.14, CI 0.91-1.43). However, associations persisted between TNM N-status and both recurrence (HR 1.58, CI 1.21-2.06) and CRC-specific death (HR 1.59, CI 1.19-2.12). CONCLUSIONS: No further prognostic information was conferred by ALN status in patients with stage III CRC beyond that provided by TNM N status. ALN status is not considered to be a useful additional component in routine TNM staging of CRC.

Recurrence and colon cancer-specific death in patients with large bowel obstruction requiring urgent operation: a competing risks analysis.

AIM: Clinical presentation with large bowel obstruction has been proposed as a predictor of poor long-term oncological outcomes after resection for colorectal cancer. This study examines the association between obstruction and recurrence and cancer-specific death after resection for colon cancer. METHOD: Consecutive patients who underwent resection for colon cancer between 1995 and 2014 were drawn from a prospectively recorded hospital database with all surviving patients followed for at least 5 years. The outcomes of tumour recurrence and colon cancer-specific death were assessed by competing risks multivariable techniques with adjustment for potential clinical and pathological confounding variables. RESULTS: Recurrence occurred in 271 of 1485 patients who had a potentially curative resection. In bivariate analysis, obstruction was significantly associated with recurrence [hazard ratio (HR) 2.23, CI 1.52-3.26, p < 0.001] but this association became nonsignificant after adjustment for confounders (HR 1.53, CI 0.95-2.46, p = 0.080). Colon cancer-specific death occurred in 238 of 295 patients who had a noncurative resection. Obstruction was not significantly associated with cancer-specific death (HR 1.02, CI 0.72-1.45, p = 0.903). In patients who had a noncurative resection, the competing risks incidence of colon cancer-specific death was not significantly greater in obstructed than in unobstructed patients (HR 1.02, CI 0.72-1.45, p = 0.903). CONCLUSION: Whilst the immediate clinical challenge of an individual patient presenting with large bowel obstruction must be addressed by the surgeon, the patient's long-term oncological outcomes are unrelated to obstruction per se.

[Primary liposarcomas of the digestive tract: Diversity of clinicopathological presentations and diagnostic challenges]. / Liposarcomes primitifs du tube digestif : diversité des présentations clinicopathologiques et challenges diagnostiques.

Sarcomas are rare tumours that represent less than 1% of all malignant tumours in adults. Liposarcomas are among the most common malignant mesenchymal tumours. They are preferentially located in the limbs and the retroperitoneum. Liposarcomas primarily arising in the digestive tract are exceptional with a few cases reported in the literature. Their clinical presentation is variable and the symptoms are not specific. Anatomopathological examination remains the gold standard for the diagnosis and the classification of these tumours, which are divided into 5 histological types according to the 5th edition of the WHO classification of soft tissue tumours. We report two observations of unusual digestive liposarcomas, located in the oesophagus and the colon, emphasizing the variability of the diagnostic challenges, depending on the clinical presentation, the histological type and the analysed material.

Near-Field Thermophotovoltaic Conversion with High Electrical Power Density and Cell Efficiency above 14.

A huge amount of thermal energy is available close to material surfaces in radiative and nonradiative states, which can be useful for matter characterization or energy harvesting. Even though a full class of novel nanoengineered devices has been predicted over the last two decades for exploiting near-field thermal photons, efficient near-field thermophotovoltaic conversion could not be achieved experimentally until now. Here, we realize a proof of principle by using a micrometer-sized indium antimonide photovoltaic cell cooled at 77 K and approached at nanometer distances from a hot (∼730 K) graphite microsphere emitter. We demonstrate a near-field power conversion efficiency of the cell above 14% and unprecedented electrical power density outputs (0.75 W cm-2), which are orders of magnitude larger than all previous attempts. These results highlight that near-field thermophotovoltaic converters are now competing with other thermal-to-electrical conversion devices and also pave the way for efficient photoelectric detection of near-field thermal photons.

Radiative heat transfer at the nanoscale: experimental trends and challenges.

Energy transport theories are being revisited at the nanoscale, as macroscopic laws known for a century are broken at dimensions smaller than those associated with energy carriers. For thermal radiation, where the typical dimension is provided by Wien's wavelength, Planck's law and associated concepts describing surface-to-surface radiative transfer have to be replaced by a full electromagnetic framework capturing near-field radiative heat transfer (photon tunnelling between close bodies), interference effects and sub-wavelength thermal emission (emitting body of small size). It is only during the last decade that nanotechnology has allowed for many experimental verifications - with a recent boom - of the large increase of radiative heat transfer at the nanoscale. In this minireview, we highlight the parameter space that has been investigated until now, showing that it is limited in terms of inter-body distance, temperature and object size, and provide clues about possible thermal-energy harvesting, sensing and management applications. We also provide an outlook on open topics, underlining some difficulties in applying single-wavelength approaches to broadband thermal emitters while acknowledging the promise of thermal nanophotonics and observing that molecular/chemical viewpoints have been hardly addressed.

Rate of dissemination and prognosis in early and advanced stage colorectal cancer based on microsatellite instability status: systematic review and meta-analysis.

INTRODUCTION: For the past two decades, microsatellite instability (MSI) has been reported as a robust clinical biomarker associated with survival advantage attributed to its immunogenicity. However, MSI is also associated with high-risk adverse pathological features (poorly differentiated, mucinous, signet cell, higher grade) and exhibits a double-edged sword phenomenon. We performed a systematic review and meta-analysis to evaluate the rate of dissemination and the prognosis of early and advanced stage colorectal cancer based on MSI status. METHODS: A systematic literature search of original studies was performed on Ovid searching MEDLINE, Embase, Cochrane Database of Systematic Reviews, American College of Physicians ACP Journal Club, Database of Abstracts of Reviews of Effects DARE, Clinical Trials databases from inception of database to June 2019. Colorectal cancer, microsatellite instability, genomic instability and DNA mismatch repair were used as key words or MeSH terms. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were pooled using a random-effects model with odds ratio (OR) as the effect size. Statistical analysis was performed using RevMan ver 5.3 Cochrane Collaboration. RESULTS: From 5288 studies, 136 met the inclusion criteria (n = 92,035; MSI-H 11,746 (13%)). Overall, MSI-H was associated with improved OS (OR, 0.81; 95% CI 0.73-0.90), DFS (OR, 0.73; 95% CI 0.66-0.81) and DSS (OR, 0.69; 95% CI 0.52-0.90). Importantly, MSI-H had a protective effect against dissemination with a significantly lower rate of lymph node and distant metastases. By stage, the protective effect of MSI-H in terms of OS and DFS was observed clearly in stage II and stage III. Survival in stage I CRC was excellent irrespective of MSI status. In stage IV CRC, without immunotherapy, MSI-H was not associated with any survival benefit. CONCLUSIONS: MSI-H CRC was associated with an overall survival benefit with a lower rate of dissemination. Survival benefit was clearly evident in both stage II and III CRC, but MSI-H was neither a robust prognostic marker in stage I nor stage IV CRC without immunotherapy.