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Background/aim: Adoptive immunotherapy of cancer is evolving with the development of novel technologies that generate proliferation of large numbers of αβ and γδ T cells. We evaluated the safety and efficacy of the combination of adoptive immunotherapy using αβ T cells with chemotherapy for stage IV colorectal cancer (CRC)., Patients and Methods: Fifteen patients with advanced or recurrent CRC received XELOX + bevacizumab + ex vivo expanded αβ T lymphocytes as a first-line chemoimmunotherapy., Results: Median age of the 15 patients (4 men, 11 women) was 65 years (range=49-80). Median progression-free survival was 21.3 months. Response rate was 80% (complete response (CR)=26.7%, partial response (PR)=53.3%, stable disease (SD)=20% and progressive disease (PD)=0%). Most adverse events were mild to moderate regarding their intensity and immunotherapy-associated toxicity was minimal., Conclusion: Combination of adoptive αβ T cell immunotherapy with chemotherapy for stage IV CRC is feasible and safe., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Numbness and pain are currently evaluated using subjective methods such as the visual analog scale (VAS). However, because assessment of pain can vary greatly depending on the mood and physical state of the patient at the time of assessment, it is best to evaluate pain objectively. pain vision PS-2100 (PV) is an analytical instrument that was designed to quantitatively and objectively assess sense perception and nociception in patients. The present study examined the correlation of subjective and objective assessment of oxaliplatin-induced peripheral neuropathy (PN) using VAS and PV, respectively. The mean VAS and PV scores of PN were 20.5 (range 0-100) and 27.9 (range 0-416), respectively. The partial correlation coefficient was 0.274 (p = 0.0003). No strong correlation was observed between the results and a weak correlation was observed between VAS and PV.

Background: Dihydropyrimidine dehydrogenase (DPD) degrades approximately 85% of administered 5-fluorouracil (5-FU). With a reported high mortality rate, chemotherapy is generally contraindicated for patients with DPD deficiency., Patients and Methods: Chemotherapy was initiated for a 73-year-old man with DPD deficiency. Capecitabine was administered in incrementally increasing doses, beginning with a single pill while monitoring plasma 5-FU concentration, and neutrophil and platelet counts., Results: DPD protein level was 2.35 U/mg. After increasing the capecitabine dose to 1,800 mg, oxaliplatin and bevacizumab were added. Subsequent DPD protein measurement showed that the level had increased to approximately 12-fold the one before chemotherapy. Sequencing of all 23 exons of DPYD gene revealed a mutation of guanine to thymine in exon 11 (1156 G>T)., Conclusion: This is the first report to indicate that DPD activity can be induced. These findings may provide early indications of a new method for chemotherapy for DPD-deficient patients., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The aim of the present study was to estimate the effect of the perioperative administration of probiotics in patients undergoing colorectal cancer (CRC) surgery. The study focused on a total of 156 consecutive surgeries carried out from among all the elective CRC surgeries performed between April 2009 and March 2013. The patients involved in surgeries undertaken between April 2009 and October 2011 were placed in the non-probiotic group (group A, 81 patients) and those involved in surgeries between November 2011 and March 2013 were placed in the probiotic group (group B, 75 patients). Postoperative infectious complications were recorded, and the immune responses and fecal microbiota were determined. A breakdown of infectious complications showed that 21 (13.5%) patients experienced superficial incisional surgical site infections (SSIs), of which 16 patients were from group A (19.8%), and five patients from group B (6.7%) (P=0.016). The ImmuKnow® adenosine triphosphate values peaked on the first postoperative day (POD) in both groups. In group A, the ImmuKnow value of the first POD was increased significantly compared with the preoperative value (P=0.022). In group B, the value of the first POD did not increase compared with the preoperative value (P=0.28). In conclusion, probiotic treatment can reduce superficial incisional SSIs in patients undergoing CRC surgery. Perioperative probiotic treatment can enhance immune responses and improve the intestinal microbial environment.

Purpose: Neutropenia is a major factor affecting continuation of chemotherapy for colorectal cancer. In many clinical trials, a neutrophil count of >1500 is targeted for continuation; for a count of <1500, medication is commonly discontinued. However, there is no definitive evidence supporting the need for a neutrophil count of 1500 for continuation of chemotherapy. In the clinical trials that we conducted, we discontinued chemotherapy when the neutrophil count was <1000 (grade 3); for a count of 1000-1500 (grade 2), chemotherapy was continued. Therefore, even practical treatment uses the same setting. Our aim was to examine neutrophil counts during continuation of chemotherapy in colorectal cancer patients with counts of 1000-1500 and to assess the need for discontinuation of medication for neutrophil counts in this range. Moreover, we examined neutrophil counts during the previous course of chemotherapy when they fell below 1000., Methods: The study included 144 patients who received XELOX + bevacizumab therapy and XELOX therapy for advanced or recurrent colorectal cancer., Results: Thirty (20.8 %) patients had neutrophil counts of 1000-1500. One (3.3 %) of 30 patients had a neutrophil count of <1000 during the following course of chemotherapy. Moreover, among the patients with neutrophil counts of <1000, 27.3 % had counts of 1000-1500 during the previous course of chemotherapy and 72.7 % had counts of >1500., Conclusions: Based on these results, grade 2 neutropenia cannot predict the risk of grade 3 neutropenia. Continuation of chemotherapy in patients with neutrophil counts of 1000-1500 may be appropriate, and discontinuation of therapy is not always required.

Background: Repeated venous punctures are usually required during chemotherapy administration for cancer patients. Central venous catheters and implantable port systems have substantially facilitated vascular access, and safe, easy-to-handle port systems have become an integral part of daily clinical routines in oncology. However, several serious complications are associated with central venous ports (CV-ports), and recent developments of combined oral capecitabine and oxaliplatin (XELOX) therapies allow CV-port-free administration. In this study, the safety and efficacy of CV-port-free chemotherapy administration via the median cubital vein was assessed in metastatic colorectal cancer patients., Methods: This study included 144 patients who received XELOX + bevacizumab (BV) or XELOX therapy for metastatic colorectal cancer without CV-port implantation., Results: Eighty-five patients experienced transient vascular pain. The drip infusion route was switched to the opposite side following vascular pain in only 1 patient. No patients required CV-port implantation or delayed treatment due to adverse events associated with drug administration via the peripheral vein. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 12.5 and 17.4 % of patients, respectively., Conclusions: Port-free-chemotherapy administration via the median cubital vein is appropriate for patients with colorectal cancer, thereby avoiding complications associated with CV-ports.

The aim of the present study was to measure adenosine triphosphate (ATP) levels in CD4 + T cells as a marker of T-cell activity following surgery for colorectal cancer using the ImmuKnow assay kit. A total of 16 consecutive patients who underwent surgical resection for colorectal cancer between August and December, 2012 were enrolled in this study, of whom 7 underwent laparoscopic resection and 9 underwent open abdominal surgery. The intracellular ATP levels in CD4 + T-lymphocytes were measured using the ImmuKnow assay kit preoperatively and on the 1st, 4th and 8th postoperative days, as were the white blood cell (WBC) count, lymphocyte count and C-reactive protein (CRP) levels. The ATP level of the CD4 + T-cells was significantly elevated on the 1st day following surgery compared to the preoperative level (P<0.01) and gradually returned to preoperative levels; the lymphocyte count was significantly decreased on the 1st postoperative day (P<0.001). In addition, the ImmuKnow assay demonstrated that only the ATP level, but not the WBC count, lymphocyte count or CRP level, exhibited a significant difference on the 1st (P=0.080) and 8th (P=0.042) postoperative days between the laparoscopic and open abdominal surgery groups. In conclusion, the ATP level of CD4 + T-lymphocytes was increased in response to surgical stress, in tandem with a decrease in the lymphocyte count. Therefore, the ImmuKnow assay kit may be clinically applicable for monitoring the immune response following surgery, as it exhibits a higher sensitivity compared to other assays.

Here we report a case of unresected gastric cancer that maintained long tumor dormancy by use of paclitaxel+S-1 combination therapy. A 58-year-old woman was admitted to the hospital for peritoneal dissemination of unresectable gastric cancer. The patient further showed ileus with peritoneal dissemination in computed tomography(CT), and we performed resection of the intestine to release the stenosis. In addition, combination chemotherapy using paclitaxel(60mg/m2, weekly) and S-1(80mg/m2, every 2 weeks)was started after the operation. The patient was discharged from the hospital 7 3 days after the operation, and we continued combination chemotherapy as an outpatient over the following 3 years without serious side effects. Furthermore, tumor makers for gastric cancer were stable, although we could not examine tumor size since the patient rejected examinations such as CT. After 3 years, the patient was admitted to the hospital with cholecystitis, and we were able to evaluate the benefit of the chemotherapy against gastric cancer. The tumor size clearly remained unchanged compared to previous measurements, suggesting that the tumor maintained dormancy in this case.

Background: Past reports showed that the baroreflex continuously regulates hemodynamics during exercise. However, it is still clinically unclear. If baroreflex mechanism is able to influence actually exercise cardiovascular control, baroreflex sympathetic and/or parasympathetic function relates to response to exercise. Therefore, we examined the relationship of heat rate changes to both blood pressure increment and decrement with tolerance and chronotropic response to peak exercise in patients with heart disease., Methods: In 25 male heart disease patients (60 ± 9 years) without decompensated heart failure, baroreceptor reflex sensitivity (BRS ms mmHg(-1) ) was measured by reflex heart rate responses to changes in blood pressure after phenylephrine (P-BRS) and nitroglycerin (N-BRS) injection, respectively. Symptom-limited treadmill exercise test was performed according to Bruce's protocol., Results: (i) The absolute values of blood pressure change after the administrations were similar between the agents because the dosages of nitroglycerin and phenylephrine were set to equalize absolute changes in blood pressure. (ii) In this study population, the ratio of N-BRS to P-BRS was not significantly correlated with hypertension and diabetes mellitus. (iii) Exercise capacity (METs) (r= -0.626) and heart rate response to exercise per METs (r=0.670) was significantly related to N-BRS but not to P-BRS., Conclusion: We found that the abnormality of baroreflex function in the presence of blood pressure decrements can lead to insufficient capacity and easy sympathetic activation during exercise., (© 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Background: Heart rate recovery (HRR) after exercise is known as a predictor of cardiac death in patients with heart disease. The mechanism is not fully understood, although a parasympathetic mechanism has been reported. To elucidate the factors that influence HRR, we evaluated the relationship of HRR with exercise performance and plasma norepinephrine (NE), lactic acid and B-type natriuretic peptide (BNP) responses to exercise testing., Methods: The study population consisted of 52 male patients (age 58 +/- 9.6 years) who had experienced myocardial infarction without residual ischemia, uncompensated heart failure or atrial fibrillation. All subjects underwent a symptom-limited cardiopulmonary exercise test without a cool-down period and echocardiography. NE, lactic acid and BNP were measured at rest and at peak exercise., Results: HRR did not correlate with the left ventricular ejection fraction, peak VO(2), lactic acid and BNP. HRR significantly correlated with the increment in heart rate (HR) from rest to peak exercise (DeltaHR) (r=0.30, p<0.05). When we divided DeltaHR into two phases at the anaerobic threshold (AT), HRR significantly correlated with DeltaHR (peak-AT) (r=0.409, p<0.01), but not with DeltaHR (AT-rest). There was a significant negative correlation between HRR and NE both at rest and at peak exercise (r=-0.286, p<0.05, r=-0.310, p<0.05). HRR was also correlated significantly with DeltaHR/logDeltaNE as an index of sensitivity to NE (r=0.421, p<0.01). Based on multiple regression analysis, DeltaHR and logDeltaNE predicted HRR (R(2)=0.467, p=0.0027)., Conclusions: Present findings suggest that enhanced sympathetic excitation at maximum exercise suppresses parasympathetic reactivation and results in attenuation of HRR.

Background: Recent studies indicated that excessive oxidative stress in an animal heart failure model injures both the sympathetic nerve endings and receptors, resulting in disturbance of norepinephrine release and sensitivity to norepinephrine. However, it has not been clarified whether this phenomenon is expressed clinically in patients with heart disease. Therefore, we examined the efficacy of ascorbic acid administration as an antioxidant vitamin in relation to the heart rate and norepinephrine response to exercise in patients after myocardial infarction., Methods: In this randomized crossover trial, 21 male patients who had had myocardial infarction underwent symptom-limited ergometer cardiopulmonary exercise testing twice, that is, without and with ascorbic acid (2 g) administration. Plasma norepinephrine concentrations were assessed at rest and at peak exercise, and heart rate responsiveness to the norepinephrine increment from rest to peak exercise (DeltaHR/logDeltaNE) was calculated., Results: In the exercise test after ascorbic acid administration, peak oxygen consumption (VO(2)) improved over baseline. Ascorbic acid administration significantly increased the change in heart rate and norepinephrine from rest to peak exercise and DeltaHR/logDeltaNE. The increment in heart rate was significantly correlated with peak VO(2) in each test., Conclusion: Ascorbic acid intake before exercise improved exercise capacity through enhancement of the heart rate and norepinephrine response to exercise in patients after myocardial infarction. These findings suggest that ascorbic acid intake improves sympathetic dysfunction resulting from injury by excessive oxidative stress after myocardial infarction.

Purpose: It is thought that the mechanisms responsible for impaired chronotropic response to exercise are related to disturbance of cardiovascular autonomic regulation such as the baroreflex. However, it is still unclear whether the baroreflex mechanisms modulate heart rate (HR) responses to exercise via vagal and/or sympathetic alteration. We therefore investigated the effects of baroreflex sensitivity (BRS) on the exercise HR response in the early phase of vagal deactivation and in the later phase of sympathetic excitation via metabolic stimulation., Methods: Twenty-four patients (18 males and 6 females, age 59+/-9 years) with heart disease underwent symptom-limited treadmill exercise testing according to the Bruce protocol, and BRS was measured utilizing the phenylephrine method. Subjects were grouped by their resting BRS value: 12 with normal BRS (> or =6 ms/mmHg) and 12 with depressed BRS (<6 ms/mmHg). The HR response to exercise was assessed using two parameters: the increment in HR during exercise and the ratio of HR response to the metabolic reserve (chronotropic index)., Results: (1) In the patients with depressed BRS, the HR responses within 1 min after the start of exercise and from 1 min to peak exercise were attenuated compared with those having a normal BRS (15+/-8 vs. 24+/-8 bpm and 36+/-9 vs. 47+/-15 bpm, respectively). (2) The chronotropic index in the patients with depressed BRS was lower than in those with normal BRS (0.50+/-0.14 vs. 0.64+/-0.08)., Conclusion: These findings suggest that impaired BRS modulates both the parasympathetic influence in early exercise and sympathetic effects in the later phase on HR response to exercise.