(R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice.

Chronic social isolation increases the risk of mental health problems, including cognitive impairments and depression. While subanesthetic ketamine is considered effective for cognitive impairments in patients with depression, the neural mechanisms underlying its effects are not well understood. Here we identified unique activation of the anterior insular cortex (aIC) as a characteristic feature in brain-wide regions of mice reared in social isolation and treated with (R)-ketamine, a ketamine enantiomer. Using fiber photometry recording on freely moving mice, we found that social isolation attenuates aIC neuronal activation upon social contact and that (R)-ketamine, but not (S)-ketamine, is able to counteracts this reduction. (R)-ketamine facilitated social cognition in social isolation-reared mice during the social memory test. aIC inactivation offset the effect of (R)-ketamine on social memory. Our results suggest that (R)-ketamine has promising potential as an effective intervention for social cognitive deficits by restoring aIC function.

The Majority of the Serine/Threonine Phosphorylation Sites in Bcl11b Protein Are Dispensable for the Differentiation of T Cells.

Posttranslational modification, such as phosphorylation, is an important biological event that modulates and diversifies protein function. Bcl11b protein is a zinc-finger transcription factor that plays a crucial role in early T cell development and the segregation of T cell subsets. Bcl11b possesses at least 25 serine/threonine (S/T) residues that can be phosphorylated upon TCR stimulation. To understand the physiological relevance of the phosphorylation on Bcl11b protein, we replaced S/T residues with alanine (A) by targeting murine Bcl11b gene in embryonic stem cells. By combinational targeting of exons 2 and 4 in the Bcl11b gene, we generated a mouse strain, Bcl11b-phosphorylation site mutation mice, in which 23 S/T residues were replaced with A residues. Such extensive manipulation left only five putative phosphorylated residues, two of which were specific for mutant protein, and resulted in reduced amounts of Bcl11b protein. However, primary T cell development in the thymus, as well as the maintenance of peripheral T cells, remained intact even after loss of major physiological phosphorylation. In addition, in vitro differentiation of CD4+ naive T cells into effector Th cell subsets-Th1, Th2, Th17, and regulatory T-was comparable between wild-type and Bcl11b-phosphorylation site mutation mice. These findings indicate that the physiological phosphorylation on major 23 S/T residues in Bcl11b is dispensable for Bcl11b functions in early T cell development and effector Th cell differentiation.

The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients.

BACKGROUND: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab. OBJECTIVE: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment. METHODS: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment. RESULTS: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/µL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen. CONCLUSION: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.

Consensus Paper: Cerebellum and Reward.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs.

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

The impact of renal function on initial therapy in transplant-ineligible multiple myeloma patients.

The prognosis for multiple myeloma (MM) patients has improved with the advent of new drugs, but the prognosis with renal impairment (RI) is poor. The choice of treatment in such cases is critical, but there are no set criteria. We examined the impact of RI on initial therapy in transplant-ineligible MM patients. We selected symptomatic MM patients who met the following criteria: age ≥ 65 years, fit, and ineligible for transplantation from the database. We analyzed the impact of age, treatment, International Staging System (ISS) stage, karyotype abnormalities, performance status, and estimated glomerular filtration rate (GFR < 50 or ≥ 50 ml/min/1.73m2) on overall survival (OS). We also analyzed the OS by eGFR for each treatment. We selected 349 symptomatic MM patients. The regimens used were lenalidomide, bortezomib and dexamethasone (RVd), daratumumab, bortezomib, melphalan, and prednisolone (D-VMP), daratumumab, lenalidomide and dexamethasone (D-Rd) and daratumumab, bortezomib, and dexamethasone (D-Vd) in 184, 41, 74 and 50 patients, respectively. The median age was 74 years old; ISS stage was I/II/III in 85/112/131 patients; and 161 patients showed eGFR < 50. The OS was shorter with ISS stage III (p = 0.029) and eGFR < 50 (p < 0.001) by multivariate analysis. The OS under the RVd/D-Rd regimens were significantly shorter for patients with eGFR < 50, but OS under the D-VMP/D-Vd regimens were not significantly different between patients with eGFR < 50 and eGFR ≥ 50. The OS of the transplant-ineligible MM patients with higher ISS stage and RI was poor. Initial treatment with a D-VMP/D-Vd regimen might be less affected by RI.

Proposal of the novel predictive model for postoperative pancreatic fistula in distal pancreatectomy for pancreatic tumor based on preoperative imaging parameters and stapler handling.

BACKGROUND: Distal pancreatectomy (DP) using linear staplers is widely performed; however, postoperative pancreatic fistulas (POPF) remain an issue. This study aimed to analyze preoperative risk factors for POPF and assess stapler handling. METHODS: We retrospectively analyzed consecutive patients who underwent DP for pancreatic tumors using a linear stapler between 2014 and 2022. Preoperative measurements included pancreas-to-muscle signal intensity ratio (SIR) on fat-suppressed T1-weighted magnetic resonance imaging (MRI). The main outcome was clinically relevant POPF of the 2016 International Study Group of Pancreatic Fistulas definition. The predictive ability of the model was compared with the distal fistula risk score (D-FRS) by using the area under the receiver operating characteristic curve (AUROC). RESULTS: Among the 81 patients, POPF occurred in 31 (38.2%). Multivariate analysis identified computed tomography-measured pancreatic thickness (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.05-1.61, p = 0.009) and SIR on T1-weighted MRI (OR 6.85, 95% CI 1.71-27.4, p = 0.002) as preoperative predictors. A novel preoperative model, "Thickness × MRI (TM)"-index, was established by multiplying these two variables. The TM-index exhibited the highest predictability preoperatively (AUROC 0.757, 95% CI 0.649-0.867). In the intraoperative variable analyses, TM-index (p < 0.001), thin cartridge application (p = 0.032), and short pre-firing compression (p = 0.047) were identified as significant risk factors for POPF. The model's AUROC combined with these two stapler handling methods was higher than D-FRS (0.851 vs. 0.660, p = 0.006). CONCLUSIONS: The novel preoperative model exhibited excellent predictability. Thick cartridge use and long pre-firing compression were protective factors against POPF. This model may facilitate preventive surgical strategy development to reduce POPF.

Japanese survey of perioperative complications and ureteral stricture after ureteroscopy with laser lithotripsy for upper urinary tract stones in multicenter collaborative study.

OBJECTIVES: This study aimed to investigate perioperative complications and the details of postoperative ureteral stricture after ureteroscopy with laser lithotripsy (URS-L) for upper urinary tract stones in Japan. METHODS: Patient data on intra- and postoperative complications after ureteroscopy using URS-L were retrospectively collected from multiple centers in Japan between April 2017 and March 2020 with the cooperation of the Japanese Society of Endourology and Robotics. Data included the number of patients undergoing URS-L, number and type of intra- and postoperative complications, and detailed characteristics of postoperative ureteral stricture. RESULTS: In total, 14 125 patients underwent URS-L over 3 years at 82 institutions. Annual URS-L numbers gradually increased from 4419 in 2017, to 4760 in 2018, and 4946 in 2019. The total complication rate was 10.5%, which was divided into intra-operative complications in 1.40% and postoperative complications in 9.18%. The annual incidences of intra- and postoperative complications were not significantly different from year to year (p = 0.314 and p = 0.112). Ureteral perforation, ureteral avulsion, and the intra-operative conversion rate were 1.35%, 0.03%, and 0.02%, respectively. Fever >38°C, septic shock, blood transfusion, and postoperative mortality were 7.44%, 0.81%, 0.07%, and 0.04%, respectively. Ureteral stricture occurred in 0.8% of cases. The median length of stricture site was 10.0 mm and the success rate of stricture treatment was 54.6%. CONCLUSION: Although URS-L utilization has increased in Japan, the annual complication rate has remained steady. Although URS-L is a useful and less invasive procedure, devastating complications can still occur.

The effectiveness of a self-reported questionnaire on masticatory function in health examinations.

Periodontal diseases have been reported to be lifestyle-related and associated with metabolic syndrome (MetS). The introduction of dental checkups in a health checkup program may create a synergistic effect and aid the prevention of MetS. In Japan, a chewing function questionnaire has now been introduced into the national health checkup program. The purpose of this study was to investigate whether the questionnaire reflects dental and oral conditions and whether it helps improve general and oral health. A total of 6599 subjects who underwent health checkups or guidance specified by the National Health Insurance of Japan for two consecutive years were included. A single comprehensive question to evaluate masticatory function was asked. Medical and dental examinations and insurance data were collected and used for analysis. In terms of masticatory function during chewing, 82.3% of subjects experienced no problems, 17.3% experienced some difficulty, and 0.4% experienced severe problems. There was a significant relationship between the questionnaire response and dental examinations results for several items of examination. The overall dental consultation rate after health screening was 42.3%. Improvement in periodontal disease was achieved in those who reported some problems with chewing function. Improvement in blood pressure was also observed in those who reported some problem with chewing function and subsequently had a dental consultation. The results of this study indicate that questionnaires on masticatory function reflect the status of dental and oral health. In addition, the results suggested that questionnaire results are potentially linked to improvement in dental and oral health status, and improvement in MetS.

[The Successful Reduction of Resected Lung Volume for Intralobar Pulmonary Sequestration with Infrared Thoracoscope].

A 59-year-old male patient was referred to our hospital for further examinations and treatment due to an abnormal shadow detected in his left lower lung lobe on computed tomography. The patient was diagnosed with intralobar pulmonary sequestration and scheduled for an operation. During the surgery, after resection of the aberrant artery, indocyanine green was intravenously injected, and the border between normal lung and sequestrated lung was clearly identified by an infrared thoracoscope. Subsequently, wedge resection was performed, and the patient was discharged on postoperative day 5. Spirometry performed 6 months after the surgery indicated that the patient's lung function was well-preserved compared to the preoperative status.

[Successful Closure of Postpneumonectomy Bronchopleural Fistula with Inserting Technique of Omental Pedicle Flap into the Right Main Bronchus:Report of a Case].

A 67-year-old male was admitted to our hospital for the treatment of pyothorax due to bronchopleural fistula at right main bronchus after pneumonectomy for lung cancer( squamous cell carcinoma, pathological stageⅢB). After tube drainage and fenestration, we performed operation to close large diameter fistula, that was almost fully opened stump of the right main bronchus. Omental flap was sutured roughly to the fistula with four stiches and inserted into the bronchus lumen, and covered with latissimus dorsi muscle flap to fix omental pedicle flap and additionally performed thoracoplasty to close the residual space of the pleural cavity. Fistula at the stump became airtight after operation and pyothorax was cured, so our method was thought to be available to close large diameter bronchopleural fistula with omental pedicle flap.

Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

Practical Implications of the Update to the 2015 Japan Standard Population: Mortality Archive From 1950 to 2020 in Japan.

BACKGROUND: The 2015 Japan Standard Population (JSP) was established in response to changes in the age structure. However, the effects of major updates, especially the recategorization of older age groups, for interpreting various health metrics have not been clarified. METHODS: Population data were collected and estimated for older age categories (85-89, 90-94, and ≥95 years). Data on the number of deaths were also collected from the Vital Statistics. We recalculated the all-cause and leading cause-specific age-standardized mortality rate (ASMR) using the 2015 JSP by the direct standardization method for data from 1950 to 2020. We compared ASMRs calculated using the 2015 JSP with those calculated using the 1985 JSP. Pearson's correlation coefficients were used to evaluate the consistency of mortality trends between the 2015 and 1985 JSPs. RESULTS: The absolute all-cause ASMRs calculated using the 2015 JSP were 2.22-3.00 times higher than those calculated using the 1985 JSP. The ASMR ratios increased gradually over time. While trends in all-cause and cause-specific ASMRs calculated using the 2015 JSP and 1985 JSP were generally highly correlated (Pearson's correlation coefficient [r] = 0.993 for all-cause), correlations were relatively low for malignant neoplasms (r = 0.720 for men and r = 0.581 for women) and pneumonia/bronchitis (r = 0.543 for men and r = 0.559 for women) due to non-monotonous trends over time and fluctuations in earlier time periods. CONCLUSION: The effect of introducing the new JSP for interpreting trends in all-cause mortality was considered minimal. However, caution is needed when interpreting trends in some cause-specific mortality rates.

Estimation of Socioeconomic Inequalities in Mortality in Japan Using National Census-linked Longitudinal Mortality Data.

BACKGROUND: We aimed to develop census-linked longitudinal mortality data for Japan and assess their validity as a new resource for estimating socioeconomic inequalities in health. METHODS: Using deterministic linkage, we identified, from national censuses for 2000 and 2010 and national death records, persons and deceased persons who had unique personal identifiers (generated using sex, birth year/month, address, and marital status). For the period 2010-2015, 1,537,337 Japanese men and women aged 30-79 years (1.9% in national census) were extracted to represent the sample population. This population was weighted to adjust for confounding factors. We estimated age-standardized mortality rates (ASMRs) by education level and occupational class. The slope index of inequality (SII) and relative index inequality (RII) by educational level were calculated as inequality measures. RESULTS: The reweighted sample population's mortality rates were somewhat higher than those of the complete registry, especially in younger age-groups and for external causes. All-cause ASMRs (per 100,000 person-years) for individuals aged 40-79 years with high, middle, and low education levels were 1,078 (95% confidence interval [CI], 1,051-1,105), 1,299 (95% CI, 1,279-1,320), and 1,670 (95% CI, 1,634-1,707) for men, and 561 (95% CI, 536-587), 601 (95% CI, 589-613), and 777 (95% CI, 745-808) for women, respectively, during 2010-2015. SII and RII by educational level increased among both sexes between 2000-2005 and 2010-2015, which indicates that mortality inequalities increased. CONCLUSION: The developed census-linked longitudinal mortality data provide new estimates of socioeconomic inequalities in Japan that can be triangulated with estimates obtained with other methods.

Socioeconomic inequalities in self-rated health in Japan, 32 European countries and the United States: an international comparative study.

AIMS: Japan is known as a country with low self-rated health despite high life expectancy. We compared socioeconomic inequalities in self-rated health in Japan with those in 32 European countries and the US using nationally representative samples. METHODS: We analysed individual data from the Comprehensive Survey of Living Conditions (Japan), the European Union Statistics on Income and Living Conditions, and the Behavioral Risk Factor Surveillance System (US) in 2016. We used ordered logistic regression models with four ordinal categories of self-rated health as an outcome, and educational level or occupational class as independent variables, controlling for age. RESULTS: In Japan, about half the population perceived their health as 'fair', which was much higher than in Europe (≈20-40%). The odds ratios of lower self-rated health among less educated men compared with more educated were 1.72 (95% confidence interval (CI) 1.61-1.85) in Japan, and ranged from 1.67 to 4.74 in Europe (pooled; 2.10 (95% CI 2.01-2.20)), and 6.65 (95% CI 6.22-7.12) in the US. The odds ratios of lower self-rated health among less educated women were 1.79 (95% CI 1.65-1.95) in Japan, and ranged from 1.89 to 5.30 in Europe (pooled; 2.43 (95% CI 2.33-2.54)), and 8.82 (95% CI 8.29-9.38) in the US. Socioeconomic inequalities were large when self-rated health was low for European countries, but Japan and the US did not follow the pattern. CONCLUSIONS: Japan has similar socioeconomic gradient patterns to European countries for self-rated health, and our findings revealed smaller socioeconomic inequalities in self-rated health in Japan compared with those in western countries.

[Prevalence of COVID-19 vaccination and approval rating of the social implementation of its certification: the Japan COVID-19 and Society Internet Survey (JACSIS) in September and October 2021].

Objective　We aimed to investigate the prevalence of COVID-19 vaccination and approval rating of the social implementation of its certification to stimulate economic activities such as travel and restaurant use ("vaccine passport").Methods　Using data from the Japan COVID-19 and Society Internet Survey (JACSIS) conducted in September-October 2021, we calculated the prevalence of the COVID-19 vaccination and prevalence ratios by educational level and occupation. We also analyzed the reasons for (not) being vaccinated. In addition, we examined the association between the percentage of respondents who thought that the "vaccine passport" should be used for economic recovery and socioeconomic status/trust in government vaccine information.Results　Of 27,423 survey participants (aged 20-79 years; 13,884 women and 13,539 men), the prevalence of COVID-19 vaccination was 74.8%, whereas 1,695 (6.2%) "wanted to be vaccinated after seeing how it went," and 1,742 (6.3%) indicated an "unwillingness to vaccinate." The prevalence of COVID-19 vaccination did not differ between women and men. In addition, the prevalence among people who graduated from university/graduate school was significantly higher than that of high school graduates (adjusted prevalence ratio, 1.09; 95% confidence interval (95% CI): 1.07-1.12). Regarding occupation, the adjusted prevalence ratio of "professional/technical" to "office workers" was 1.05 (95% CI: 1.01-1.07). Among the "vaccinated (twice)" group, the most common reason for vaccination was "do not want to infect family members or others" (53.0%). Among the "unwillingness to vaccinate" group, the largest percentage indicated "because I am worried about adverse reactions" (44.5%). Among the "unwillingness to vaccinate" group, only 12.2% of respondents answered that the "vaccine passport" should be utilized for economic recovery, while 41.8% of the "vaccinated (twice)" group agreed with having the "vaccine passport" (adjusted prevalence ratio, 0.30; 95% CI: 0.25-0.37). By occupation, the highest percentage was the "sales and marketing" workers (40.4%). This proportion was significantly higher in the "strongly or fairly agree" group (49.5%) for the reliability of vaccine information from the government than in the "neither agree nor disagree" group (27.5%, P<0.01).Conclusion　Differences in the prevalence of COVID-19 vaccination were found by socioeconomic status. In addition, trust in government information was associated with an approval rating of the social implementation of the "vaccine passport" in Japan. However, the results suggest that citizens' expectations and interests are not high regarding the use of the "vaccine passport" to stimulate economic activity.

[Geographic information in National Cancer Registry data: Overseas examples and challenges in Japan].

Worldwide, research based on geographic information of official statistical data, including cancer registries, is utilized for cancer control and public health policies. The National Cancer Registry of Japan was launched in 2016, making it possible to use data on cancer incidence systematically. Given the nature of this comprehensive survey, the usefulness of the National Cancer Registry would be further enhanced when it is utilized at small-regional levels, such as in municipalities or even smaller geographical units. It is essential to maintain a balance between privacy protection and data usability. Currently, the national and prefectural councils determine the availability of the data from the National Cancer Registry at the small-regional level on an individual application basis. Under this framework, use of the data is often restricted or declined. This paper showcases three model countries where geographic information obtained from cancer registry data are widely utilized: the United States, Canada, and the United Kingdom. It further discusses measures to ensure that data are effectively used, without compromising data privacy. In the three countries, data-providing systems have been established to compile the necessary data from the cancer registry and other linked databases, in accordance with the purpose of use. The relationships between healthcare access and various outcomes are elaborately examined at the small-regional level. In Japan, similar utilization of data has not been fully implemented, and there remain many hurdles to the application of the data use. For the National Cancer Registry to promote research and further enhance cancer control, it is necessary to establish a system that enables effective and safe utilization of the data from the National Cancer Registry, including linkage with other data and on-site use.

[Metastases in the Lung and Mediastinal Lymph Nodes from Breast Cancer 28 Years after the First Operation:Report of a Case].

A 76-year-old woman was pointed out a small nodule in the right lower lung lobe on a chest computed tomography( CT) for follow-up examinations of malignant thyroid lymphoma. Although she had undergone a radical mastectomy for right breast cancer 28 years previously, the nodule was suspected to be either metastatic lymphoma or primary lung cancer and thoracoscopic surgery was planned to perform. Since the intraoperative frozen section diagnosis was adenocarcinoma, right lower lobectomy and systemic lymph node dissection were performed. However, the final pathology revealed that the lesion was breast cancer metastasis and subcarinal lymph nodes were also positive for metastases.

Decreased expression of T-cell-associated immune markers predicts poor prognosis in patients with follicular lymphoma.

We previously examined the utility of rituximab-bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R-CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB-treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression-free survival (PFS) in the RB-treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8+ T-cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24-mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB-treated patients into immune IIShigh (n = 19) and IISlow (n = 20) groups. The 3-y PFS rate was significantly lower in the IISlow group than in the IIShigh group (50.0% [95% CI: 27.1-69.2%] vs. 84.2% [95% CI: 58.7-94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL patients. (UMIN:000 013 795, jRCT:051 180 181).

Novel prognostic predictor of haemoglobin-platelet index in diffuse large B-cell lymphoma, not otherwise specified: Anaemia and thrombocytopenia are associated with IL-6 production in lymphoma cells.

We previously reported that a novel haemoglobin-platelet index (HPI) based on anaemia and thrombocytopenia was useful to predict the prognosis of patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS). Here, we analyse the utility of HPI in a new validation cohort with DLBCL NOS (n  = 94). As a result, we confirm that HPI was effective for differentiating progression-free survival (PFS) and overall survival in this validation cohort. So, we further compare the utility of HPI with previously reported prognostic markers such as the National Comprehensive Center Network-International Prognostic Index (NCCN-IPI), Glasgow prognostic score (GPS), and platelet-albumin (PA) score, using a larger number of 160 patients consisting of the derivation cohort (n  = 66) and a validation cohort (n  = 94). As a result, the patients with a higher HPI score had significantly worse outcomes, and HPI predicted the prognosis of DLBCL NOS independently of NCCN-IPI. HPI was more sensitive than GPS and almost the same as PA score in predicting PFS. Moreover, the patients whose lymphoma cells were positive for interleukin-6 (IL-6) (75/111 cases) judged by immunohistochemical staining had significantly lower haemoglobin levels and platelet counts than IL-6-negative cases (36/111 cases), suggesting the involvement of IL-6 produced by lymphoma cells in anaemia and thrombocytopenia in DLBCL NOS patients.