Characteristics and Prognosis of Colorectal Cancer Associated With Rheumatic Disease

It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression.Key words: Colorectal cancer, Rheumatic disease, Host immunity, PrognosisIt is well known that host immunity plays an important role in defenses against the development and progression of cancer. The degree of lymphocyte infiltration into tumors has been reported to correlate with improvements of patient survival.¹ In carcinogen-induced mouse models of cancer, primary tumor susceptibility has been found to be enhanced in immunocompromised mice; conversely, the capacity for such tumors to grow after transplantation into wild-type mice is reduced.^2,3 Although cancer cells originate from autologous normal tissue, the immune system can recognize even minimal cellular alterations, distinguish cancerous from normal cells, and elicit an immune response.In autoimmune diseases represented by rheumatic disease (RD), the immune system loses the ability to distinguish nonself from self, eliciting an immune response against self-antigens; in this process, there is a possibility that immune defenses against non-normal cells are lost or impaired, facilitating the development and progression of cancer. In addition, the development of RD associated with cancer has been reported, and as its development is dependent on the production of substances such as hormones, peptides, autocrine and paracrine mediators, and antibodies or the stimulation of cytotoxic lymphocytes, the condition is known as paraneoplastic rheumatic syndrome. In such cases, RD tends to be less responsive to therapy than its nonparaneoplastic equivalents, and instead, treatment of the underlying cancer usually results in regression of RD.^4,5 Thus, it is postulated that RD and cancer are closely associated. However, only a few reports on the incidence and risk of cancer among patients with RD exist,^6,7 and the characteristics and prognosis of colorectal cancer (CRC) in these patients remain to be elucidated.In the present study, we investigated the development of CRC in the background of an immunologic disorder caused by RD, with the hypothesis that patients with CRC and autoimmune diseases such as RD will have a poorer prognosis than those without RD, as a result of depressed antitumor immunity caused by immune system incompetence. Thus, we aimed to clarify the features and prognosis of CRC-associated RD, and for this purpose, we compared the clinicopathologic features of patients with CRC with or without underlying RD.     

Perioperative Allogeneic Blood Transfusion Is Associated With Surgical Site Infection After Abdominoperineal Resection—a Space for the Implementation of Patient Blood Management Strategies

Allogeneic blood transfusion (ABT) has been reported as a major risk factor for surgical site infection (SSI) in patients undergoing colorectal surgery. However, the association of ABT with SSI in patients undergoing abdominoperineal resection (APR) and total pelvic exenteration (TPE) still remains to be evaluated. Here, we aim to elucidate this association. The medical records of all patients undergoing APR and TPE at our institution in the period between January 2000 and December 2012 were reviewed. Patients without SSI (no SSI group) were compared with patients who developed SSI (SSI group), in terms of clinicopathologic features, including ABT. In addition, data for 262 patients who underwent transabdominal rectal resection at our institution in the same period were also enrolled, and their data on differential leukocyte counts were evaluated. Multivariate analysis showed that intraoperative transfusion was an independent predictive factor for SSI after APR and TPE (P = 0.004). In addition, the first–operative day lymphocyte count of patients undergoing APR, TPE, and transabdominal rectal resection was significantly higher in nontransfusion patients compared with transfusion ones (P = 0.026). ABT in the perioperative period of APR and TPE may have an important immunomodulatory effect, leading to an increased incidence of SSI. This fact should be carefully considered, and efforts to avoid allogeneic blood exposure while still achieving adequate patient blood management would be very important for patients undergoing APR and TPE as well.Key words: Colorectal cancer, Abdominoperineal resection, Surgical site infection, Allogeneic blood transfusion, Patient blood managementPostoperative surgical site infection (SSI) is one of the most frequent complications associated with various surgical procedures, and it results in adverse outcomes, including longer hospital stay, higher health care costs, and increased surgical mortality.¹ It is one of the most frequent nosocomial complications, accounting for almost one fifth of all health care–associated infections.² Colon surgery and rectal surgery are associated with higher SSI rates compared with most other abdominal procedures, with 5% to 25% of colon and rectal surgery patients developing incisional and organ/space SSI.^3–5 Moreover, the incidence of overall SSI was reported to be higher in rectal surgery patients (17%–28%) than in colonic surgery patients (9%–23%),^3,5,6 with especially higher overall SSI rates observed in patients undergoing abdominoperineal resection (APR; 12%–51%).^7–9 These are attributed to the high infection rates of the perineal wound, reported to be as high as 21%.¹⁰ Thus, the incidence of SSI associated with APR should be the highest among the various abdominal operative procedures.Various risk factors for postoperative SSI in colorectal surgery were reported previously. Open surgery,^10–12 perioperative allogeneic blood transfusion (ABT),^4,10,12 and prolonged operation time^4,9 have been found to be risk factors for SSI in a number of studies. Although several preceding reports have investigated the risk factors for SSI associated with APR, the reported independent risk factors varied among the studies. Although a number of studies have reported on the role of ABT as a strong risk factor for incisional SSI in colorectal surgery,^13,14 only one study has investigated on its relevance to the onset of incisional SSI after APR procedure; but this study failed to demonstrate a significant association. Presently, therefore, the role of ABT as a potential risk factor for incisional SSI in APR remains to be elucidated, and doing so will be very important for the implementation of measures to achieve patient blood management in this group of patients.In this study, we aimed to elucidate the risk factors for SSI in patients receiving APR, especially focusing on ABT.     

JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities

Obesity is a serious global health issue; however, the roles of genetics and epigenetics in the onset and progression of obesity are still not completely understood. The aim of this study was to determine the role of Kdm4b, which belongs to a subfamily of histone demethylases, in adipogenesis and fat metabolism in vivo. We established conditional Kdm4b knockout mice. Inactivation of Kdm4b in adipocytes (K4bKO) induced profound obesity in mice on a high fat diet (HFD). The HFD‐fed K4bKO mice exhibited an increased volume of fat mass and higher expression levels of adipogenesis‐related genes. In contrast, the genes involved in energy expenditure and mitochondrial functions were down‐regulated. Supporting these findings, the energy expenditure of Kdm4b‐deficient cells was markedly decreased. In addition, progression of glucose intolerance and hepatic steatosis with hepatocellular damages was observed. These data indicate that Kdm4b is a critical regulator of systemic metabolism via enhancing energy expenditure in adipocytes.     

Effect of mother's voice on neonatal respiratory activity and EEG delta amplitude

While the influence of the mother's voice on neonatal heart‐rate response and its relevant activity on cerebral cortex and the autonomic nervous system (ANS) are well known, few studies have assessed its influence on respiratory activity. We investigated the relationship among the respiration rate, the delta wave amplitudes through electroencephalography, and the basal state of ANS through the respiratory variability index while 22 full‐term neonates hear their mother's voice and an unknown voice. It was found that when respiratory variability was large, a transient (<5 s) change in respiration rates was observed in response to an unknown voice, while a greater increase in the delta wave amplitude was observed in the frontal lobe than the parietal one in response to the mother's voice. Conversely, when respiratory variability was small, a sustained increase (>10 s) in respiration rates was observed in response to the mother's voice, while a greater increase in the delta wave amplitude was found in both the frontal and parietal lobes. These results suggest that the basal state of ANS influences the latency of increases in respiration rates. Furthermore, induced by the mother's voice, transient increases in respiration rates are reduced in association with frontal lobe activity, and sustained increases in respiration rates are promoted in association with frontal and parietal lobe activities.     

Characteristics of spontaneous calcium oscillations in renal tubular epithelial cells

Background

The kidney is a major organ involved in calcium (Ca²⁺) metabolism. Ca²⁺ is transported through renal tubular epithelial cells. The intracellular free calcium concentration ([Ca²⁺]_i) is tightly controlled at a low concentration, but transient increases and oscillations in [Ca²⁺]_i are induced by various conditions. In this study, we investigated the mechanisms underlying the spontaneous [Ca²⁺]_i oscillations observed in MDCK cells.

Methods

[Ca²⁺]_i was monitored in fura-2-loaded Madin-Darby canine kidney (MDCK) cells using a calcium imaging system. We investigated the mechanism by which [Ca²⁺]_i changed by applying drugs or by changing the extracellular Ca²⁺ concentration.

Results

Spontaneous [Ca²⁺]_i oscillations occurred in MDCK cells. The oscillations occurred irregularly and were not transmitted to neighboring cells. Spontaneous [Ca²⁺]_i oscillations in MDCK cells were initiated by Ca²⁺ release from ryanodine/IP₃-sensitive intracellular calcium stores, and their frequency was largely unaffected by the extracellular Ca²⁺ concentration. Moreover, the frequency of the oscillations was increased by extracellular nucleotide, but was decreased when the nucleotides were removed.

Conclusions

Our study suggested that [Ca²⁺]_i release from ryanodine/IP₃-sensitive intracellular calcium stores mediates spontaneous [Ca²⁺]_i oscillations in MDCK cells. Calcium oscillations may be associated with the function of the renal tubular epithelial cells.     

Association of Eating Alone With Depression Among Older Adults Living Alone: Role of Poor Social Networks

ObjectivesEating alone is associated with an increased risk of depression symptoms. This association may be confounded by poor social networks. The present study aimed to determine the role of poor social networks in the association of eating alone with depression symptoms, focusing on cohabitation status.MethodsSeven hundred and ten community-dwelling older adults were categorized according to their eating style and social network size, evaluated using an abbreviated version of the Lubben Social Network Scale, with poor social network size (defined as the lowest quartile). Living arrangements and depression symptoms, detected using the Zung Self-Rating Depression Scale, were also assessed.ResultsA mixed-design two-way analysis of covariance (eating style and social network size factors) for the depression scale score, adjusted by covariates, yielded significant effects of social network size and eating style without interaction. Greater depression scores were observed in eating alone and poor social network size. Analysis of participants living with others showed the same results. However, among older adults living alone, only a significant main effect of social network size was observed; poor social network size resulted in greater depression scores irrespective of eating style.ConclusionsPoor social network size, and not eating alone, was associated with greater depression symptoms among older adults living alone, whereas both factors may increase depression symptoms among older adults living with others. Poor social network size may show a stronger influence on depression than eating alone in older adults living alone; thus, social network size is an important health indicator.Key words: eating alone, social network, living alone, depression, older adults