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The present study investigated the effects of dietary supplementation combined with fish oil containing relatively low levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the inflammatory and nutritional status of patients with epithelial cancer. Fish oil capsules (498 mg EPA and 213 mg DHA) and dietary supplements (100 kcal and 5 g protein) were administered for 8 weeks to 20 patients with cancer and inflammation [C-reactive protein (CRP) ≥0.30 mg/dl]. Blood EPA levels increased significantly after 4 and 8 weeks, while no significant differences were observed in log-transformed (log) CRP levels, which were the major inflammatory indices in these patients. A declining trend was observed at 8 weeks after excluding 2 patients with suspected infection (P=0.06). A significant increase was observed from week 0 to week 8 for log interleukin-6 (IL-6) levels. After excluding the 2 patients with suspected infection, no significant difference was observed when comparing week 0 to week 8 for log IL-6. No deterioration in albumin or pre-albumin levels was observed. These results suggest that although suppression of acute inflammation associated with infection is difficult, intake of relatively low EPA and DHA supplements may be effective for mild chronic inflammation in patients with epithelial cancer without infection. Large-scale randomized clinical trials are required to make the final decision regarding efficacy. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; 06/07/2018, UMIN000033309).

Background Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell‐to‐cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. Methods We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre‐operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR‐203 expression levels in CRC tissues and pre‐operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR‐203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR‐203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. Results A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35–89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well‐established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour–node–metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P

MINI: In the present study, we systemically and comprehensively evaluated the prognostic significance of a combination of inflammatory factors using preoperative blood examination, and focused on the potential feasibility of our newly developed lymphocyte-CRP ratio (LCR) as a prognostic biomarker in CRC patients. We have firstly identified that a combination of lymphocytic counts along with CRP levels, which we defined as LCR, is a more reliable indicator of poor prognosis compared with other combinations of inflammatory markers, in CRC patients. Furthermore, preoperative LCR could also identify CRC patients who are at higher risk for postoperative infectious complications. Background Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. Method In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. Results A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. Conclusion Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.

Background: Sarcopenia is defined as the loss of skeletal muscle mass, accompanied by decreased muscle strength, and consists of myopenia and myosteatosis. Recent evidence has suggested the predictive value of sarcopenia for the risk of perioperative and oncological outcomes in various malignancies. The aim of this study was to clarify the clinical impact of myopenia and myosteatosis in colorectal cancer (CRC) patients. Methods: We analyzed the preoperative psoas muscle mass index and intramuscular adipose tissue content using preoperative computed tomography images from 308 CRC patients using statistical methods. Results: Despite no significant correlation between myosteatosis and prognosis, preoperative myopenia significantly correlated with clinicopathological factors for disease development, including advanced tumor depth (P = 0.009), presence of lymphatic vessel invasion (P = 0.006), distant metastasis (P = 0.0007), and advanced stage classification (P = 0.013). Presence of preoperative myopenia was an independent prognostic factor for both cancer‐specific survival (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 1.5–5.05, P = 0.001) and disease‐free survival (HR: 3.15, 95% CI: 1.8–5.51, P = 0.0001), and was an independent risk factor for postoperative infectious complications in CRC patients (odds ratio: 2.03, 95% CI:1.17–3.55, P = 0.013). Furthermore, these findings were successfully validated using propensity score matching analysis. Conclusions: Preoperative myopenia could be useful for perioperative management, and quantification of preoperative skeletal muscle mass could identify patients as a high risk for perioperative and oncological outcomes in CRC patients.

Serum transthyretin (TTR), also known as prealbumin, is a reliable nutritional indicator and an independent prognostic factor for maintenance hemodialysis patients. However, we recently reported that serum TTR levels did not affect protein-energy wasting (PEW). In this study, we investigated factors affecting serum TTR levels in 60 maintenance hemodialysis patients. The patients were divided into High-TTR and Low-TTR groups according to the median serum TTR level. Albumin levels were significantly higher and C-reactive protein (CRP) levels were significantly lower in the High-TTR group than in the Low-TTR group. Although body fat mass was significantly higher in the High-TTR group than in the Low-TTR group, no significant difference in body fat ratio were observed. These findings suggest that body fat mass is related to serum TTR levels, apart from factors such as albumin and CRP levels, which showed correlations with serum TTR levels. Because body fat mass is related to better survival in maintenance hemodialysis patients, it may contribute to the prognostic value of serum TTR levels. In addition, in such patients, it may be important to evaluate body fat mass rather than body fat ratio and to maintain the minimum necessary body fat mass. J. Med. Invest. 64: 222-227, August, 2017.

Treatment of cancer patients undergoing chemotherapy with L-carnitine (LC) supplementation is becoming increasingly popular in the clinic. The present study aimed to examine the possible effects of polymorphisms in CPT1B and CPT2 (CPT1B G320D, S427C, c.282-18 C>T, and p.E531K, and CPT2 V368I) on the plasma concentration of carnitine in humans. The subjects were the 218 participants of the Iga Cohort Study. Differences in plasma-free carnitine levels by genotype were examined. Genotyping was conducted by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). The plasma carnitine levels were significantly higher in males (PT, or p.E531K, nor by CPT2 V368I genotypes (P=0.133, P=0.538, P=0.636, P=0.509, and P=0.398, respectively). When analysis of covariance (ANCOVA) adjusted for age and sex was applied, the plasma levels of carnitine were not statistically significantly different according to these genotypes (P=0.299, P=0.715, P=0.980, P=0.851, and P=0.674, respectively). The present study did not identify any statistically significant differences in plasma carnitine levels between subjects with different CPT1 and CPT2 genotypes, suggesting that there may be no need to tailor treatments to patients’ genotypes when determining the dose/amount of LC to be administered to cancer patients undergoing palliative care.

Summary Background & aims In dialysis patients, malnutrition is a poor prognostic factor. In patients with chronic kidney disease (CKD), malnutrition is qualitatively different from general malnutrition, which is defined as “Protein-Energy Wasting (PEW).” Dietary therapy for the enhancement of PEW requires the aggressive intake of protein. Conversely, as protein intake and phosphorus intake correlate positively, increasing the protein intake increases the phosphorus intake, which is a poor prognostic factor in dialysis patients. One of the treatments for hyperphosphatemia in dialysis patients is the intake restriction of phosphorus by dietary counseling. However, protein uptake to maintain and augment the nutritional status and the protein intake restriction to correct hyperphosphatemia are contradictory treatments. Hence, this study aims to investigate the effects of PEW and hyperphosphatemia on the prognosis in hemodialysis patients. Methods We enrolled 60 outpatients who underwent maintenance hemodialysis for 6 months (May–November 2012) at Iga City General Hospital (Mie, Japan). In November 2012, we assessed the presence or absence of PEW and hyperphosphatemia in patients and evaluated the survival rate over the next 5 years. Results Overall, 10 patients (17%) were diagnosed as PEW. While 17 patients (28%) exhibited average phosphorus level >6.0 mg/dL (hyperphosphatemia). The 5-year survival rate was 30% in the PEW group, 66% in the non-PEW group, 57% in the hyperphosphatemia group, and 61% in the non-hyperphosphatemia group. A statistically significant difference existed between the PEW and non-PEW groups (P = 0.021). However, we observed no significant difference between the hyperphosphatemia and non-hyperphosphatemia groups. Conclusions This study suggests that PEW affects the prognosis more than hyperphosphatemia in maintenance hemodialysis patients. The normalization of the serum phosphorus level by the protein intake restriction could prevent secondary hyperparathyroidism and vascular calcification. Conversely, restricting the protein intake poses a risk of malnutrition. In fact, early death occurred in patients with PEW in this study. Perhaps, patients with PEW should prioritize improving their nutritional status rather than controlling the serum phosphorus level.

We used clinical data from Iga General Hospital to examine the association between polymorphisms in MTR (methionine synthase) A2756G (rs1805087), MTRR (methionine synthase reductase) His595Tyr (rs10380), MTHFR (methylenetetrahydrofolate reductase) C677T (rs1801133), MTHFR A1298C (rs1801131) and SHMT (serine hydroxymethyltransferase) C1420T (rs1979277), which are genes involved in folate metabolism, and the risk of weight loss in patients with gastrointestinal cancers, with the aim of establishing personalized palliative care for each patient based on genetic information. The data from 59 patients (37 males and 22 females) with gastrointestinal cancers who visited the outpatient clinic for cancer chemotherapy and palliative care at Iga General Hospital from December 2011 to August 2015 were analyzed. There was no significant association between the single nucleotide polymorphisms (SNPs) in the folate metabolizing genes examined and weight loss defined as weight loss of more than 5 percent or more than 10 percent during the first 6 months after initiation of chemotherapy. We did not detect any significant association between any of the SNPs examined and overall survival of patients. The present study indicated that these SNPs have relatively limited or no roles in the genesis of cachexia in patients with gastrointestinal cancers; however, further investigations into the roles of these folate metabolizing genes in the context of cancer palliative care, from clinical, biological and epidemiological viewpoints are warranted.

Purpose Despite recent progress in the diagnosis and treatment of colorectal cancer (CRC), the prognosis remains poor, and metastatic recurrence is the leading cause of poor prognosis. We systemically evaluated the levels of differentially-expressed serum cytokines using array-based techniques to identify a novel and reliable serum biomarker with which to predict metastasis and poor outcomes of CRC. Methods We examined cytokine profiling using preoperative serum from two different cohorts to identify differentially-expressed serum cytokines in patients with metastatic CRC. In the validation phase, serum monocyte chemotactic protein-4 (MCP-4) concentration was assessed in 194 patients by enzyme-linked immunosorbent assay, and its relationships with clinicopathological findings were investigated. Results In discovery phase, three cytokines were differentially expressed in serum from patients with metastatic CRC. In validation phase, high MCP-4 was significantly associated with older age, advanced T stage, distant metastasis, and UICC stage. Cox regression analysis showed that elevated MCP-4 was an independent prognostic factor of disease-free survival and overall survival. Furthermore, logistic regression analysis revealed that high serum MCP-4 was an independent predictor of distant metastasis. Conclusion Quantification of serum MCP-4 concentration might support the early detection/prediction of recurrence and may contribute to the prediction of clinical outcomes in CRC. J. Surg. Oncol. 2016;114:483–489. © 2016 Wiley Periodicals, Inc.

Gastrointestinal cancer is one of the most common causes of mortality globally. The present study examined the influence of cytokine genetic polymorphisms [interleukin (IL)-1B C-31T, IL-1RN VNTR, IL-6 C-634G, IL-8 T-251A, IL-10 T-819C and IL-10 A-1082G] on clinical outcomes in patients with gastrointestinal cancer in palliative care. A total of 59 patients with gastrointestinal cancer who were admitted to Iga City General Hospital were analyzed. Genotyping was conducted using a polymerase chain reaction with confronting two-pair primers. Patients with at least one IL-1RN 2 allele demonstrated a significantly better survival (P=0.0275) while those with IL-6−634 G/G demonstrated a worse survival (P=0.0024). Multivariate analyses using the Cox proportional hazard model revealed that those with at least one IL-1RN 2 allele, IL-6−634 G/G or IL-10−1082 A/G had a significantly elevated adjusted hazard ratio of 9.20 (P=0.014), 41.01 (P=0.001) or 6.49 (P=0.046), respectively, compared with those with each homozygous wild-type polymorphism. In addition, the evaluation of weight loss by genotype revealed the potential influence of IL-10 T-819C genotype (P=0.072). IL-1RN, IL-6 and IL-10 polymorphisms were associated with the survival of patients with gastrointestinal cancer, suggesting the clinical feasibility of genetic testing in patients with gastrointestinal cancer in palliative care.

Severe malnutrition accompanied by sarcopenia and cachexia, is strongly associated with the surgical and oncological outcomes in cancer patients. The aim of the present study was to clarify the clinical significance of sarcopenia and its correlation with sarcopenia-associated miRNA in colorectal cancer (CRC). A total of 167 CRC patients were enrolled in the present study. We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC). The expression of miR-21 in CRC tissues and preoperative serum was evaluated using quantitative PCR. Despite the lack of significant correlation between IMAC and disease-correlated factors, decreased PMI was significantly associated with well-established clinicopathological factors for disease progression. Decreased PMI was an independent prognostic factor for both overall survival and disease-free survival and was an independent risk factor for various types of metastasis. In contrast to the expression of tissue miR-21, the expression of serum miR-21 was significantly increased in CRC patients with low PMI. Furthermore, postoperative PMI was drastically improved compared with preoperative PMI in CRC patients with potentially curative resections. In conclusion, skeletal muscle mass may be a prognostic and predictive biomarker for distant metastasis in CRC patients and quantification of serum miR-21 expression could help clinicians make decisions regarding nutrition intervention strategies in CRC patients.

Colony‑stimulating‑factor‑1 (CSF‑1) is a hematopoietic growth factor that exerts its effects through the c‑fms/CSF‑1 receptor (CSF‑1R). The CSF‑1/CSF‑1R axis is thought to be involved in the development of several types of cancer. This study aimed to clarify the clinical and biological significance of the CSF‑1/CSF‑1R axis in gastric cancer (GC). For this purpose, we evaluated CSF‑1 and CSF‑1R expression in GC tissues from 148 patients by RT‑qPCR and immunohistochemistry. The biological roles of the CSF‑1/CSF‑1R axis were investigated by measuring the cell proliferation and migration, and anoikis resistance in a human GC cell line following treatment with recombinant human CSF‑1 and/or CSF‑1R inhibitor. The results revealed that an elevated expression of CSF‑1 or CSF‑1R significantly correlated with disease progression and with a poor overall survival (OS, P=0.037 and 0.016, respectively) and disease‑free survival (DFS, P

Background/aim This study aimed to clarify the potential of modified Glasgow Prognostic Score (mGPS) as a prognostic biomarker and reveal the significance of fish oil (FO)-enriched nutrition in colorectal cancer (CRC). Patients and methods A total of 738 CRC patients from three different patient cohorts, including 670 patients in the biomarker study and 68 patients in the nutrition-intervention study, were analyzed. Results High preoperative mGPS was significantly correlated with well-recognized disease progression factors and advanced UICC stage classification. In addition, high mGPS was an independent prognostic factor in both cohorts, especially in stage III and IV patients. These statuses were maintained in postoperative course and correlated with sarcopenia. Furthermore, FO-enriched nutrition suppressed systemic inflammatory reaction and improved skeletal muscle mass and prognosis, especially in CRC patients with mGPS 1 or 2. Conclusion Assessment of mGPS could identify patients with high-risk CRC, who might be candidates for FO-enriched nutrition.

A 41-year-old man presented to our hospital with lower abdominal pain and a high-grade fever. Physical examination revealed rebound tenderness and guarding in the lower abdomen. Abdominal X-ray examination showed a radiopaque object in the right lower quadrant of the abdomen. Abdominal computed tomography (CT) demonstrated that the object had a strong artifact with over 10,000 Hounsfield units, as well as ascites around the terminal ileum. We diagnosed acute peritonitis with a suspicion of the perforation due to unknown foreign body and performed an emergency laparotomy. Operative findings showed a contained perforation of a phlegmonous appendicitis, and appendectomy was performed. The resected specimen demonstrated that the appendix contained a fecalith, and histopathological examination showed the crystal structure of barium sulfate in the lumen of the appendix. Unfortunately, we did not obtain the history of screening for gastric cancer using a barium examination one month prior to our appendectomy. Our experience demonstrates the importance of establishing a history of barium examinations of the gastrointestinal tract in a patient with a radiopaque object in the right lower quadrant of the abdomen for early diagnosis of barium appendicitis. Additionally, early diagnosis of barium appendicitis may affect the selection of surgical procedures.

Objective: Cancer patients often suffer from chronic inflammation, anorexia and the resultant decrease of nutrient intake, followed by weight loss and muscle wasting called “sarcopenia”. Such conditions are known as “cachexia”. In this study, we examined the associations between genetic polymorphisms of AKT1 rs1130233, ICAM1 rs281432, SELP rs6128 and TNSRSF1A rs4149570, which are reportedly associated with cachexia in Caucasians, together with LIF rs929271, in Japanese gastrointestinal cancer patients with palliative care. Methods: The study subjects were 59 patients (37 males and 22 females) with gastrointestinal cancers who visited the outpatient clinic at Iga General Hospital from December 2011 till August 2015. Genotypings for AKT1 rs1130233, ICAM1 rs281432, SELP rs6128, TNSRSF1A rs4149570 and LIF rs929271 were conducted with polymerase chain reaction with confronting two-pair primers (PCR-CTPP) or the Taqman SNP Genotyping assay. Associations of these SNPs with patients’ prognosis as well as weight loss defined as weight loss more than 5 percent during 6 months after the initiation of chemotherapy were evaluated. Results: A significant increase in the risk of 5% weight loss was observed in those with A/G genotype AKT1 rs1130233 polymorphism (AKT1 A/G vs. G/G, adjusted odds ratio [aOR]=7.11; 95%CI: 1.41-35.7), or in those with at least one A allele of AKT1 rs1130233 (AKT1 A/G+A/A vs. G/G, aOR=4.57; 95% CI: 1.14-18.3) when adjusted for age, sex and UICC clinical stage 4. There was no statistically significant correlation of the polymorphisms examined with patients’ survival. Conclusion: The present study revealed that AKT1 rs1130233 A allele may play a key role in the development of cancer cachexia. Given the involvement of AKT1 in the development of cancer as well as in apoptosis, it would be worth studying the roles of this molecule in human cancers further from clinical, epidemiological and biological viewpoints in the near future.

Key Clinical Message Four patients with gastric cancer underwent 5-fluorouracil and cisplatin-based chemoradiotherapy followed by surgery. Expression analysis of chemoradiosensitivity related genes in residual cancer using formalin-fixed paraffin-embedded specimens may be useful when determining a chemotherapy regimen for disease recurrence after chemoradiotherapy for gastric cancer.

Our aim was to examine the association between postoperative infection and preoperative systemic inflammation in patients undergoing resection of gastrointestinal cancer. We studied 862 patients who underwent elective gastrointestinal cancer surgery at six institutions. The levels of C-reactive protein and albumin were included as parameters of preoperative systemic inflammation measured using the Glasgow prognostic score. The Glasgow prognostic score was calculated based on the admission data as follows: patients with an elevated level of C-reactive protein (>1.0 mg/dl) and hypoalbuminemia (

Lymph node status is the most significant prognostic factor of colorectal cancer. However, there is a risk of disease understaging if the extent of lymph node assessment is sub-optimal. Preoperative C-reactive protein (CRP) is known to be a useful tool in predicting postoperative outcomes in patients with colorectal cancer. We retrospectively evaluated whether CRP adds to prognosis information in stage I–III colorectal cancer patients with poor lymph node assessment. In stages I–III, multivariate analysis revealed that CRP-positive status and advanced T-stage were factors that independently affected survival. In stage III, univariate analysis revealed that lymph node number retrieval and lymph node ratio were factors that affected survival. However, CRP positivity was the only independent factor for survival. CRP positivity did not predict poor prognosis in stage II or III patients with adequate lymph node retrieval. By contrast, the prognosis of CRP-positive patients was poorer than that of CRP-negative patients in stage II and III, with inadequate lymph node retrieval. CRP is an independent prognostic marker in patients with stage I–III, II or III colorectal cancer. The evaluation of CRP may provide useful information on prognosis in curative patients with an inadequate examination of lymph nodes.

Background In palliative care, prediction of life expectancy is one of the most crucial issues for patients, family and medical staff, in order to provide appropriate end-of-life care. The aim of this study was to formulate a new objective score to predict life expectancy within 1 week for terminally ill patients with cancer. Patients and methods Medical records were obtained from 187 terminally-ill patients with cancer who were admitted for palliative care. The biomarkers for a potential 'Objective Predictive Score' were assessed. Results Profiling of blood parameters demonstrated that elevated levels of alanine aminotransferase (ALT), total bilirubin (T-bil), blood urea nitrogen (BUN), creatinine (Cr) and a decreased platelet count were significantly correlated with death within 1 week in a training cohort. Our formulated Objective Predictive Score was able to predict death within 1 week with high accuracy in a training and a validation cohort. Conclusion Our scoring system might enable the assessment of prognostication with higher accuracy in a terminal care setting.

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

A 47-year-old man was admitted to the emergency room, half a day after having fallen down on his right cheek drunkenly onto a concrete block. Physical examination revealed that the contusion was limited to the right side of his face, only around the cheek, without trauma to the neck, chest or abdomen. But wide ranging tactile crepitus with severe swelling was present on his face and neck due to widely spread emphysema. Computed tomography (CT) scan revealed some fractures of maxillary antrum, facial and cervical emphysema spreading to the lower part of mediastinum. After a conservative treatment, he recovered without any severe systematic complication. It was found that the facial and cervical emphysema and pneumomediastimum completely disappeared on the follow-up CT scan, 18 days after the event.

The International Society of Renal Nutrition and Metabolism (ISRNM) has recently recommended the use of the term "protein-energy wasting" (PEW). PEW is a state of malnutrition with decreased body stores of protein and energy fuel in hemodialysis patients and is known as a risk factor for morbidity and mortality. We examined the prevalence of PEW and the characteristics of PEW patients in a hemodialysis center in Japan.Fifty-nine outpatients undergoing maintenance hemodialysis at Iga City General Hospital were evaluated. We observed their biochemical data, body composition, dietary intake, and the number of steps prospectively. PEW was defined according to ISRNM criteria.Nine patients (15% of total) were diagnosed as having PEW. Among indicators of PEW criteria, the relevance ratios of "reduced muscle mass" and "unintentional low dietary energy intake" were significantly higher in PEW than in non-PEW. The number of steps was lower, and serum levels of glucose and C-reactive protein were higher in PEW.About 15% of Japanese hemodialysis patients are estimated to have PEW. Our results suggested that major contributing factors to PEW were reduced muscle mass, unintentional low dietary energy intake, lower amount of exercise, insulin resistance, and chronic inflammation.背景与目的：国际肾营养与代谢协会（ISRNM）最近推荐使用术语“蛋白质能量 消耗（PEW）”。PEW 是血液透析患者体内蛋白质和能量储存减少的一种营养 不良状态，并且被认为是患病率和死亡率的危险因素。我们在日本的一个血液 透析中心研究了PEW 的患病率和PEW 患者的特征。方法与研究设计：我们评 估了58 名在伊贺市综合医院做维持性血液透析的门诊患者，并观察了他们的生 化数据、体成分、膳食摄入量和行走的步数。根据ISRNM 标准诊断PEW。结 果：9 名（占总数的15%）患者被诊断为PEW。在PEW 诊断标准指标中， PEW 患者“肌肉量减少”和“无意识的低膳食能量摄入”的比例高于非PEW 患者。 PEW 患者中行走的步数较低，而血清葡萄糖和C-反应蛋白水平较高。结论：约 有15%的日本血液透析患者患有PEW。我们的研究结果表明：引起PEW 的主 要因素是肌肉量减少、无意识的低膳食能量摄入、运动量低、胰岛素抵抗和慢 性炎症。.

The metastasis-associated (MTA) gene family is a critical component of the nucleosome remodeling and histone deacetylase complex, and plays an important role in metastatic processes. We systematically evaluated dysregulation of the MTA family to clarify their clinical significance in gastric cancer (GC). One hundred and forty-five patients who underwent surgery for GC were evaluated. We analyzed the expression levels of the MTA family (MTA1, 2 and 3) by qPCR in GC tissue, and the MTA1 protein expression in primary cancer and matched normal mucosa (NM) was measured using immunohistochemical analysis. The expression of all the MTA family members was significantly increased in a stage-dependent manner, and elevated expression of all of the MTA family members was correlated with metastatic factors and prognosis in GC patients. Multivariate analysis revealed that MTA1 overexpression was an independent risk factor for survival. Especially, elevated expression of MTA1 was significantly correlated with recurrence, and was an independent risk factor for lymph node metastasis. Immunohistochemical analysis demonstrated that MTA1 was predominantly expressed in the nuclei of primary GC cells but was not expressed in NM and in the cancer stroma. In conclusion, quantification of MTA expression may support the accurate diagnosis of disease staging and may help predict clinical outcomes.

Despite recent progress in the diagnosis and treatment of colorectal cancer (CRC), the prognosis remains poor, and metastatic recurrence is the leading cause of poor prognosis. We systemically evaluated the levels of differentially-expressed serum cytokines using array-based techniques to identify a novel and reliable serum biomarker with which to predict metastasis and poor outcomes of CRC.We examined cytokine profiling using preoperative serum from two different cohorts to identify differentially-expressed serum cytokines in patients with metastatic CRC. In the validation phase, serum monocyte chemotactic protein-4 (MCP-4) concentration was assessed in 194 patients by enzyme-linked immunosorbent assay, and its relationships with clinicopathological findings were investigated.In discovery phase, three cytokines were differentially expressed in serum from patients with metastatic CRC. In validation phase, high MCP-4 was significantly associated with older age, advanced T stage, distant metastasis, and UICC stage. Cox regression analysis showed that elevated MCP-4 was an independent prognostic factor of disease-free survival and overall survival. Furthermore, logistic regression analysis revealed that high serum MCP-4 was an independent predictor of distant metastasis.Quantification of serum MCP-4 concentration might support the early detection/prediction of recurrence and may contribute to the prediction of clinical outcomes in CRC. J. Surg. Oncol. 2016;114:483-489. © 2016 Wiley Periodicals, Inc.

Background and aim: Postoperative leukocytapheresis (LCAP) reduces surgical site infection (SSI) in ulcerative colitis (UC) patients undergoing proctocolectomy with ileal pouch–anal anastomosis (IPAA). To clarify the effect of postoperative LCAP on circulating neutrophils, we investigated neutrophil function before and after LCAP in UC patients undergoing proctocolectomy with IPAA. Method: Circulating neutrophils were obtained from 29 UC patients undergoing IPAA before and after postoperative LCAP. The phagocytic activity was measured using Escherichia coli BioParticles. Neutrophil viability after co-culture with E. coli was measured by flow cytometry. Inflammatory cytokines in patient serum and supernatants after co-culture of neutrophils with E. coli were measured by enzyme-linked immunosorbent assay. Results: No difference in phagocytic activity was found between preand post-LCAP neutrophils. The percentage of necrotic neutrophils was significantly decreased in post-LCAP neutrophils cocultured with E. coli. Serum neutrophil elastase (NE) after LCAP was significantly increased. No difference in cytokine production was found between pre- and post-LCAP neutrophils cocultured with E. coli. NE and tumor necrosis factor (TNF)-α levels in supernatants of post-LCAP neutrophils cocultured with E. coli were higher in patients with longer operating time and higher postoperative neutrophil count, respectively. Phagocytic activity of post-LCAP neutrophils was lower in the longer operating time group. Serum TNF-α level after LCAP was higher in the SSI group. Conclusion: Postoperative LCAP decreases the subset of circulating neutrophils, which induces necrosis against bacterial infection. This suggests a possible mechanism of prevention of SSI.

Aims To evaluate the relationship between vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) levels in gastric cancer tissue and clinicopathological features and to determine whether these factors were correlated with survival. Materials and methods We analysed tissue samples from 58 patients with gastric cancer and used 24 normal gastric mucosae as controls. Tissue levels of VEGF and HGF were measured in tissue extracts by enzyme-linked immunosorbent assay. Results HGF and VEGF levels were significantly higher in gastric cancer tissue than in matched normal gastric mucosa. VEGF levels were significantly increased in cancer tissue from cases involving lymphatic invasion. HGF levels were significantly increased according to the disease stage. Patients with high levels of VEGF or HGF showed significantly worse survival rates than patients with low levels. Using multivariate analysis, a high level of VEGF or HGF was an independent factor predicting poor survival. Conclusions Intratumoral levels of HGF and VEGF are an important prognostic determinant in gastric cancer. The current findings suggest that high concentrations of HGF and VEGF may induce aggressive tumour growth and metastasis.

CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P

Background and Objectives Distant metastatic relapse occurs in approximately 20% of rectal cancer patients treated with 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by surgery. This study aimed to investigate mRNA level of 5-FU metabolizing enzymes in post-treatment specimens and to evaluate their predictive value of distant recurrence after CRT. Methods Forty patients with rectal cancer underwent 5-FU-based CRT followed by surgery. After microdissection, total RNA of residual cancer was isolated from formalin-fixed paraffin-embedded (FFPE) specimens. Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) as 5-FU metabolizing enzyme were measured using real-time reverse transcription polymerase chain reaction. Results Patients (n = 6) who developed distant recurrence had a significantly higher TS (P = 0.01), DPD (P = 0.02), and TP (P = 0.01) levels, compared with those patients (n = 34) without recurrence. High TS, DPD, and positive lymph node metastasis (pN) were significantly poorer prognostic factors for DFS (TS: P

Hepatocellular adenoma (HCA) is a benign condition occurring most frequently in young women using oral contraceptives. We herein report the first case of a 28-year-old man with familial adenomatous polyposis (FAP) who experienced hepatocellular carcinoma (HCC) within HCA. A preoperative computed tomography scan of the abdomen disclosed a tumor measuring 5.8 cm in diameter in the left lobe of the liver. A total proctocolectomy with construction of a linear stapled J-pouch, a hand-sewn ileoanal anastomosis and a liver tumor resection were performed. The pathology of the resected specimen confirmed the diagnosis of HCA containing HCC. Five cases of HCA have been reported that developed in patients with FAP, but this is the first case of HCA containing HCC. Hepatocellular adenomas occur due to the inactivation of hepatic nuclear factor 1α, but the mechanism underlying the malignant transformation from HCA to HCC could not be identified in this case.

Stem cells are thought to contribute to tissue regeneration as well as carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC) has shown distinct characteristics compared with those of sporadic CRC. The aim of this study was to evaluate the expression of stem cell markers CD133, OCT4 and NANOG in UC-CRC and the inflamed colonic epithelium of UC patients. Total RNAs of UC-CRC (n=6), inflamed colonic epithelium (n=24), sporadic CRC (n=37) and adjacent normal colonic epithelium (n=37) were isolated from formalin-fixed, paraffin-embedded specimens using microdissection techniques in order to purify colonic epithelial cells. Relative mRNA levels of CD133 (PROM), OCT4 (POU5F1) and NANOG were measured using real-time reverse transcription polymerase chain reaction. Three stem cell markers were also investigated immunohistochemically. PROM, POU5F1 and NANOG levels were found to be significantly lower in UC-CRC than in inflamed colonic epithelium of UC patients. By contrast, sporadic CRC showed a significantly higher expression of PROM, POU5F1 and NANOG compared with adjacent normal colonic epithelium. POU5F1 and NANOG levels were significantly lower in UC-CRC than in sporadic CRC. PROM and NANOG levels in inflamed colonic epithelium were significantly higher among younger UC patients (P

Aims The mechanism of distant recurrence in rectal cancer after preoperative chemoradiotherapy (CRT) has yet to be fully elucidated. Further improvements in survival rates cannot be achieved without decreasing distant recurrence after preoperative CRT. Recently, it was reported that hypoxic conditions were correlated with cancer stem cell generation. Therefore, we investigated the correlation between the expression of CD133 and hypoxia inducible factor-1α (HIF-1α), and their association with clinical outcome. Materials and methods Fifty-two patients with rectal cancer underwent preoperative CRT. Residual cancer cells after CRT were obtained from formalin-fixed paraffin-embedded specimens using micro-dissection. The expression levels of CD133 ( PROM1 ) and HIF-1α genes were measured using real-time reverse transcription polymerase chain reaction. The correlation between expression and irradiation was evaluated using colon cancer cell lines. Immunohistochemical staining of these proteins after CRT was also investigated. Results We observed a significant inverse correlation between the gene expression of CD133 ( PROM1 ) and HIF-1α genes in residual cancer cells after CRT. Elevated CD133 gene expression was associated with distant recurrence and poor recurrence-free survival. Elevated HIF-1α gene expression was associated with poor overall survival. In vitro , the change in gene expression levels after irradiation showed inverse patterns. Immunohistochemical analyses showed that residual cancer cells strongly expressed CD133 and lacked HIF-1α expression. Conclusion Our results suggest that CD133 and HIF-1α expression is associated with tumour re-growth and distant recurrence after CRT. These results may assist in clarifying the development of future cancer therapeutics in rectal cancer patients undergoing preoperative CRT.

Although thrombus formation in vivo has recently been reported, all previous laser induced thrombus models have been associated with vessel wall disruption. This study aimed to evaluate in vivo real-time platelet aggregation after selective endothelial injury, and to visualize thrombus formation without disruption and swelling of the arterial intima induced by two-photon laser irradiation. Cecal arteriole thrombi were created in beta-actin-green fluorescent protein transgenic mice by selective endothelial injury using two-photon laser-scanning microscopy (TPLSM). The in vivo real-time process of thrombus formation was assessed. Anticoagulant drug efficiency for thrombi was also analyzed in detail. TPLSM allowed visualization of microvessel components from the arterial smooth muscle to the intimal layer. Immediately after selective laser irradiation of the intimal layer, platelet adhesion and aggregation were seen only at the area of injury of the intimal layer after forming linear adhesions downstream of the injured area. When shear stress was overcome, thrombus formation began at the downstream edge of the injured area. Thrombus volume plateaued approximately 60 min after laser irradiation. The thrombolytic effects of anticoagulant drugs were precisely assessed; therefore, our model appears the most advanced model in point of real-time imaging of pathophysiological processes in vivo currently reported. In vivo real-time imaging of thrombus formation can be achieved using TPLSM in combination with an organ stabilizing system. The high magnification and resolution of TPLSM allows investigation of the mechanisms of thrombus formation along with assessment of antithrombotic drug efficacy with little interexperimental variation.

The aim of this study was to determine if the placement of prophylactic drains influences the incidence of postoperative adverse events in neonates.Neonatal patients undergoing laparotomy between April 2000 and December 2007 were prospectively assigned to aggressive peritoneal cavity lavage, without the placement of prophylactic drains, before abdominal closure (non-drainage group, n = 111). The historical control group consisted of neonates who underwent laparotomy with routine prophylactic drain placement between January 1993 and March 2000 (drainage group, n = 87). The incidence of postoperative adverse events was compared between the two groups.There were no significant differences in the incidence of overall complications (drainage, 48%; non-drainage, 36%: p = 0.08), infectious complications (drainage, 34%; non-drainage, 26%: p = 0.20) or surgical site infections (drainage, 20%; non-drainage, 14%: p = 0.25) between the two groups. In the subgroup analysis, the incidences of total postoperative complications and infectious complications were significantly higher in the drainage group compared with the non-drainage group for upper gastrointestinal tract operations (52 vs. 20%; 39 vs. 6.7%) (p = 0.04 and 0.02, respectively).Prophylactic drainage did not reduce the incidence of postoperative complications, and the placement of drains may possibly increase the incidence of infectious complications.

Background Vascular adhesion protein-1 (VAP-1) regulates leukocyte tissue infiltration. Elevated serum soluble VAP-1 (sVAP-1) levels occur in certain diseases having an inflammatory component. We previously showed in colorectal cancer that sVAP-1 expression is significantly higher relative to controls, and this decreased expression is associated with poor prognosis and lymph node and liver metastasis. However, sVAP-1 expression has not been described for gastric cancer. This study determines the relationship between preoperative serum sVAP-1 levels and clinicopathological features and prognosis in gastric cancer. Methods Preoperative serum was collected from 107 gastric cancer patients and 33 normal controls. sVAP-1 levels were assayed by enzyme-linked immunosorbent assay. Results The mean sVAP-1 level for cancer patients was significantly higher relative to controls, and decreased with disease progression. Tumor size, serosal invasion, lymph node metastasis, peritoneal dissemination, and TNM classification was significantly correlated with sVAP-1 level. sVAP-1 is also an independent predictive marker for lymph node metastasis. Patients having low sVAP-1 levels had significantly poorer prognosis relative to patients having elevated sVAP-1 in all or stages I–III gastric cancer patients, respectively. Conclusions Low sVAP-1 levels are associated with poor prognosis in gastric cancer. Determining sVAP-1 levels may be valuable for predicting prognosis and lymph node metastasis. J. Surg. Oncol. 2011;103:695–699. © 2011 Wiley-Liss, Inc.

目的:胃癌症例における術前C-reactive protein（CRP）値と予後との関係，および，腫瘍微小環境とCRP値について検討した．方法:胃癌の診断にて胃切除を施行した91例を対象とした．術前CRP値と臨床病理学的因子，予後および，腫瘍内サイトカイン濃度（interleukin-1β，interleukin-6，interleukin-1ra）を測定し，CRP値との関連について検討した．結果:病理組織学的因子とCRP値との間に有意な関連は認めなかった．しかし，CRP高値（CRP≧1.0mg/dl）を示す症例では，有意に予後が不良であった．また，腫瘍組織内IL-1β濃度は，CRP高値例でCRP低値（CRP結論:胃癌術前CRP値は予後に影響を与えており，CRP値上昇は炎症性サイトカインを中心とする腫瘍内微小環境と密接な関係があることが示唆された．

Recent studies have revealed the Glasgow prognostic score (GPS) to aid in the prediction of postoperative outcome in colorectal cancer patients. However, whether GPS predicts poor prognosis in curative colorectal cancer patients has yet to be ascertained. Furthermore, there is no information on the association between GPS and adjuvant chemotherapy in stage II or III colorectal cancer patients. A total of 219 patients with stage II and III colorectal cancer were included in this trial. The modified GPS (mGPS) defined in this study was calculated on the basis of admission data as follows: patients with an elevated level of both C-reactive protein (0.5 mg/dl) and hypoalbuminemia (Alb

Background: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients. Methods: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis. Results: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio

The human kallikrein-related peptidases (KLK) are considered important prognostic biomarkers in cancer. The aim of the current study is to demonstrate gene expression of KLK7 in colorectal cancer (CRC) and to correlate the relative KLK7 expression level with clinicopathological factors of CRC. KLK7 messenger RNA (mRNA) expression was examined in nine CRC cancer cell lines by real-time polymerase chain reaction. The expression levels of KLK7 mRNA in cancerous tissues (n = 136) and paired normal tissues (n = 136) of CRC patients were also examined. Six of the nine cell lines expressed the KLK7 gene. KLK7 mRNA expression levels in cancer tissues were significantly higher than those in normal tissues. Multivariate analysis revealed that the KLK7 mRNA expression level in cancer was an independent prognostic factor, especially in liver metastasis. We provide evidence suggesting that KLK7 mRNA expression is correlated with prognosis in CRC patients, especially in liver metastasis.