Association between pretreatment haemoglobin levels and morphometric characteristics of the tumour, response to neoadjuvant treatment and long-term outcomes in patients with locally advanced rectal cancers

Aim The study was carried out to investigate whether pretreatment haemoglobin (Hb) levels act as a biomar- ker in the management of patients with locally advanced rectal cancer. Method\ud We prospectively collected data on all patients within our cancer network with localized low rectal cancer treated with preoperative radiotherapy/chemora- diotherapy at Mount Vernon Centre for Cancer Treat- ment between March 1994 and July 2008. Pretreatment Hb level was assessed as an independent variable for the whole study sample and dichotomised at a value of 12 g/dl. A multivariate analysis of covariance (MANCOVA) was conducted on parameters that had significant association on univariate analysis of covariance (ANCOVA) and cor- relational (Kendall tau/Pearson) analyses. Kaplan – Meier survival analysis and Cox proportional hazard models were used to determine significant prognostic markers. Statistical significance was set at 0.05. Results 463 patients (male/female 2:1; median age = 66 years, interquartile range = 56.5 – 73.0) were included in the analysis. There was significant tumour response of T stage ( P < 0.001) and N stage ( P < 0.001), with 17.6% of patients achieving a pathological complete response. Pretreatment Hb value was inversely related to the craniocaudal vertical tumour length ( P = 0.02) and pretreatment T stage of the tumour ( P = 0.01). Patients with Hb levels of < 12 g/dl and moderately differenti- ated adenocarcinoma were less responsive. Local recur- rence was more common in patients with a pretreatment Hb of < 12 g/dl (hazard ratio = 1.78) over a median follow up of 24 months, but this was not statistically significant ( P = 0.08). Conclusion The pretreatment Hb level might be used as a biomarker of rectal tumour morphology, response to neoadjuvant chemoradiation and risk of local recur- renc

Mode-switching: a new technique for electronically varying the agglomeration position in an acoustic particle manipulator

Acoustic radiation forces offer a means of manipulating particles within a fluid. Much interest in recent years has focussed on the use of radiation forces in microfluidic (or “lab on a chip”) devices. Such devices are well matched to the use of ultrasonic standing waves in which the resonant dimensions of the chamber are smaller than the ultrasonic wavelength in use. However, such devices have typically been limited to moving particles to one or two predetermined planes, whose positions are determined by acoustic pressure nodes/anti-nodes set up in the ultrasonic standing wave. In most cases devices have been designed to move particles to either the centre or (more recently) the side of a flow channel using ultrasonic frequencies that produce a half or quarter wavelength over the channel, respectively.It is demonstrated here that by rapidly switching back and forth between half and quarter wavelength frequencies – mode-switching – a new agglomeration position is established that permits beads to be brought to any arbitrary point between the half and quarter-wave nodes. This new agglomeration position is effectively a position of stable equilibrium. This has many potential applications, particularly in cell sorting and manipulation. It should also enable precise control of agglomeration position to be maintained regardless of manufacturing tolerances, temperature variations, fluid medium characteristics and particle concentration

Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines

Long COVID is characterized by the emergence of multiple debilitating symptoms following SARS-CoV-2 infection. Its etiology is unclear and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRAs) suggest a histamine-dependent mechanism that is distinct from anaphylaxis, possibly mediated by T cells, which are also regulated by histamine. T cell perturbations have been previously reported in post-viral syndromes, but the T cell landscape in patients who have recovered from mild COVID-19 and its relationship to both long COVID symptoms and any symptomatic response to HRA remain underexplored. We addressed these questions in an observational study of 65 individuals who had recovered from mild COVID-19. Participants were surveyed between 87 and 408 days after the onset of acute symptoms; none had required hospitalization, 16 had recovered uneventfully, and 49 had developed long COVID. Symptoms were quantified using a structured questionnaire and T cell subsets enumerated in a standard diagnostic assay. Patients with long-COVID had reduced CD4+ and CD8+ effector memory (EM) cell numbers and increased PD-1 (programmed cell death protein 1) expression on central memory (CM) cells, whereas the asymptomatic participants had reduced CD8+ EM cells only and increased CD28 expression on CM cells. 72% of patients with long COVID who received HRA reported clinical improvement, although T cell profiling did not clearly distinguish those who responded to HRA. This study demonstrates that T cell perturbations persist for several months after mild COVID-19 and are associated with long COVID symptoms

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m−2 bid on days 1–14 and oxaliplatin 130 mg m−2 on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m−2 bid on days 22–35 and 43–56, and oxaliplatin 50 mg m−2 on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13–36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer

Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus. Results of a post-hoc analysis from the randomized phase III ACT II trial

PURPOSE: Concurrent chemoradiation is standard-of-care for patients with squamous cell carcinoma of the anus (SCCA). Poor compliance to chemotherapy, radiotherapy treatment interruptions and unplanned breaks may impact adversely on long-term outcomes. METHODS: The ACT II trial recruited 940 patients with localized SCCA, and assigned patients to mitomycin (week 1) or cisplatin (weeks 1 and 5), with fluorouracil (weeks 1 & 5) and radiotherapy (50·4Gy in 28 fractions over 38 days). This post-hoc analysis examined the association between baseline factors (age, gender, site, T-stage and N-stage), and compliance to treatment (radiotherapy and chemotherapy), and their effects on loco-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS). Compliance was categorized into groups. Radiotherapy: 6 groups according to total dose (TD) and overall treatment time (OTT). Chemotherapy: 3 groups (A = per-protocol; B = dose reduction or delay; C = omitted). RESULTS: 931/940 patients were evaluable for radiotherapy and 936 for chemotherapy compliance. Baseline Glomerular filtration rate (GR) 42 days is associated with worse PFS and OS (HR:1.72 (95%CI:1.17-2.54), p=0.006). CONCLUSION: Poor compliance to chemotherapy and radiotherapy were associated with worse LRFFS, PFS and OS. Treatment interruptions should be minimized, and OTT and TD maintained

A micro electromagnetic generator for vibration energy harvesting

Vibration energy harvesting is receiving a considerable amount of interest as a means for powering wireless sensor nodes. This paper presents a small (component volume 0.1 cm3, practical volume 0.15 cm3) electromagnetic generator utilizing discrete components and optimized for a low ambient vibration level based upon real application data. The generator uses four magnets arranged on an etched cantilever with a wound coil located within the moving magnetic field. Magnet size and coil properties were optimized, with the final device producing 46 µW in a resistive load of 4 k? from just 0.59 m s-2 acceleration levels at its resonant frequency of 52 Hz. A voltage of 428 mVrms was obtained from the generator with a 2300 turn coil which has proved sufficient for subsequent rectification and voltage step-up circuitry. The generator delivers 30% of the power supplied from the environment to useful electrical power in the load. This generator compares very favourably with other demonstrated examples in the literature, both in terms of normalized power density and efficiency

A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study

The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m−2) administered on days 1–5 and 29–33 followed by low dose LV (20 mg m−2) and 5FU (350 mg m−2 over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6–10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26–75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m−2 when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m−2 dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m−2 (days 1–5 and 29–33). The acceptable toxicity and compliance at 18 mg m−2 recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group