Integrative analysis of spontaneous CLL regression highlights genetic and microenvironmental interdependency in CLL.

Spontaneous regression is a recognized phenomenon in chronic lymphocytic leukemia (CLL) but its biological basis remains unknown. We undertook a detailed investigation of the biological and clinical features of 20 spontaneous CLL regression cases incorporating phenotypic, functional, transcriptomic, and genomic studies at sequential time points. All spontaneously regressed tumors were IGHV-mutated with no restricted IGHV usage or B-cell receptor (BCR) stereotypy. They exhibited shortened telomeres similar to nonregressing CLL, indicating prior proliferation. They also displayed low Ki-67, CD49d, cell-surface immunoglobulin M (IgM) expression and IgM-signaling response but high CXCR4 expression, indicating low proliferative activity associated with poor migration to proliferation centers, with these features becoming increasingly marked during regression. Spontaneously regressed CLL displayed a transcriptome profile characterized by downregulation of metabolic processes as well as MYC and its downstream targets compared with nonregressing CLL. Moreover, spontaneous regression was associated with reversal of T-cell exhaustion features including reduced programmed cell death 1 expression and increased T-cell proliferation. Interestingly, archetypal CLL genomic aberrations including HIST1H1B and TP53 mutations and del(13q14) were found in some spontaneously regressing tumors, but genetic composition remained stable during regression. Conversely, a single case of CLL relapse following spontaneous regression was associated with increased BCR signaling, CLL proliferation, and clonal evolution. These observations indicate that spontaneously regressing CLL appear to undergo a period of proliferation before entering a more quiescent state, and that a complex interaction between genomic alterations and the microenvironment determines disease course. Together, the findings provide novel insight into the biological processes underpinning spontaneous CLL regression, with implications for CLL treatment.

[Employment Support for Cancer Patients].

In Japan, the number of people who suffer with cancer once in their lives has increased since 1985, and the 5-year relative survival rate for cancer patients continues to improve. As a result, there have been reports on the difficulties faced by working age patients because they attempt to simultaneously undergo cancer treatment and work. In June 2012, the Ministry of Health, Labour and Welfare published the Basic Plan to Promote Cancer Control Programs with improved cancer countermeasures for working people and children to manage problems related to the employment of cancer patients, and it has been subsequently promoting these initiatives. A report on the needs and problems faced by medical facilities regarding the employment of cancer patients, survivors, and their family members was presented at an investigative commission in August 2014 that assessed ways to support the employment of cancer patients and survivors. In February 2016, the Ministry of Health, Labour and Welfare released its guidelines on providing workplace support to people attempting to simultaneously undergo treatment and continue working. The authors conducted an interview survey of clinical nurses who provided employment and life support to cancer patients. In this study, we present examples of employment support practices provided to cancer patients by clinical nurses that we hope will be helpful to medical facilities providing such support.

[Effect of Japanese Traditional Medicine, TJ-48, on the Quality of Life of Patients with Non-Small Cell Lung Cancer Receiving Outpatient Chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy.It is very important to retain the quality of life (QOL) of these patients.Japanese traditional medicine, TJ-48, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-48 in patients with lung cancer undergoing outpatient chemotherapy is unknown. The present study was conducted to investigate the factors influencing the QOL of these patients. We used "The QOL questionnaire for cancer patients treated with anticancer drugs" (QOL-ACD) with 16 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other variables indicating "activity," "physical condition, "psychological condition,""social relationships," "psychological condition," and "face scale" were analyzed. Significant improvement was observed in the total QOL score, mainly owing to the improvement in the patients "physical condition."

[Analysis of factors associated with the quality of life in patients with non-small cell lung cancer who received outpatient pemetrexed maintenance therapy].

Increasing number of patients with advanced non-small cell lung cancer are receiving outpatient maintenance chemotherapy. It is very important to maintain these patients' quality of life(QOL). Pemetrexed has been reported to be an effective maintenance chemotherapy. However, its effects on the QOL of patients with non-small cell lung cancer who are undergoing outpatient maintenance chemotherapy are unknown; therefore, we conducted this study. To investigate factors that influence the QOL of these patients, we provided a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs(QOL-ACD)"to 7 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores, as well as other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale", were analyzed. No significant reductions in any of the factors were observed in this study.

A Method to Measure the Diffusion Coefficient in Liquids.

Molecular diffusion in liquids is a key process in numerous systems: it is often the reaction rate limiting factor in biological or chemical reaction. Molecular diffusion has been recognized as the ultimate mechanism by which substances concentration get homogenized and, thus, their mixing and dilution occur. Here, we propose a novel method to directly measure the diffusion coefficient D of solutes or suspensions in liquids. Differently from current methods, as Dynamic Light Scattering or Fluorescent Correlation Spectroscopy, our method does not rely on previous knowledge on the fluid or tracer properties, but it is based on directly measuring the concentration spatial profile of a considered tracer with optical techniques within a diffusion chamber. We test this novel method on a sample of mono-dispersed suspension of spherical colloids for which an estimate for D can be made based on Einstein-Stokes relation. We, then, use this technique to measure the diffusion coefficient of a non-spherical tracer. We further quantify mixing of the considered tracers in the confined domain of the diffusion chamber: we show that, since diffusion-limited mixing (quantified in terms of the dilution index) in a confined space happens faster than un-confined domain, the finite size of the diffusion chamber must be taken into account to properly estimate D and the tracer mixing degree.

Infective Exacerbation of Pasteurella multocida.

An 89-year-old lady presented with a one-day history of shortness of breath as well as a cough productive of brown sputum. Her medical history was significant for chronic obstructive pulmonary disease (COPD). She was in severe type one respiratory failure and blood tests revealed markedly raised inflammatory markers; however her chest X-ray was clear. On examination there was bronchial breathing with widespread crepitations and wheeze. She was treated as per an infective exacerbation of COPD. Subsequent blood cultures grew Pasteurella multocida, a common commensal in the oropharynx of domesticated animals. The patient was then asked about any contact with animals, after which she revealed she had a dog and was bitten on her left hand the day before admission. We should not forget to enquire about recent history of injuries or animal bites when patients present acutely unwell. She made a complete recovery after treatment with penicillin.