Geriatric Nutritional Risk Index Is an Independent Prognostic Factor for Patients With Esophageal Cancer Who Receive Curative Treatment.

BACKGROUND/AIM: The perioperative nutritional status has recently been reported to influence the prognosis of various types of cancer. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and overall survival (OS) and recurrence-free survival (RFS) in patients with esophageal cancer who received radical and adjuvant therapy. PATIENTS AND METHODS: Patients who underwent radical resection for esophageal cancer at our hospital (n=187) were included. Background characteristics, surgical factors, and OS were examined retrospectively. The GNRI was calculated using preoperative values, with GNRI <98 classified as low-GNRI. RESULTS: Seventy-five and 112 patients were classified into the GNRI-low and -high groups, respectively. The 3- and 5-year OS rates were 75.7% and 66.7%, respectively, in the GNRI-high group and 43.2% and 36.7% in the GNRI-low group; the difference was statistically significant (p<0.001). In the univariate and multivariate analyses, low-GNRI was selected as a risk factor for OS. The hazard ratio for low-GNRI was 2.184 (95% confidence interval=1.361-3.508, p=0.001). The 5-year RFS rate in the high- and low-GNRI groups was 54.6% and 25.0%, respectively (p=0.001). In the univariate and multivariate analyses, low-GNRI was a risk factor for RFS. The hazard ratio for low-GNRI was 1.704 (95%CI=1.121-2.590, p=0.013). Regarding the type of recurrence, lymph node recurrence was significantly more common in the low-GNRI group (p=0.008). CONCLUSION: Low-GNRI was an independent risk factor for OS and RFS after radical resection of esophageal cancer. The preoperative GNRI may be a useful prognostic factor after esophageal cancer surgery.

The clinical impacts of the prognostic nutritional index for the esophageal cancer patients who received curative treatment.

BACKGROUND: We investigated the impact of the prognostic nutritional index (PNI) on esophageal cancer survival and recurrence after curative treatment. METHODS: This study included 120 patients who underwent curative surgery followed by the adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: The PNI of 49 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rate. The OS rates at three and five years after surgery were 47.4% and 36.0% in the PNI low group, respectively, and 62.5% and 56.5% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). The RFS rates at three and five years after surgery were 31.0% and 24.8% in the PNI low group, respectively, and 50.9% and 42.8% in the PNI high group, which amounted to a statistically significant difference (P = 0.020). A multivariate analysis demonstrated that the PNI was a significant independent risk factor for the OS and a marginally significant independent risk factor forRFS. CONCLUSION: The PNI was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the PNI.

The Clinical Influence of Geriatric Nutritional Risk Index in Patients With Gastric Cancer Who Receive Curative Treatment.

BACKGROUND/AIM: We evaluated the clinical impact of the Geriatric Nutritional Risk Index (GNRI) in patients who received curative treatment and perioperative adjuvant treatment. We also investigated the association between the GNRI and the clinicopathological features of patients with GC. PATIENTS AND METHODS: This study included 280 patients who underwent curative treatment for GC between 2005 and 2020. The prognosis and clinicopathological parameters of the high-GNRI and low-GNRI groups were compared. RESULTS: In the GNRI-high group, the overall survival (OS) rates at 3 and 5 years after surgery were significantly lower (82.7% and 77.9%, respectively) than those in the GNRI-low group (56.4% and 40.8%). The GNRI was selected for the final multivariate analysis model for OS. The GNRI was also a significant prognostic factor for recurrence-free survival (RFS). The RFS rates at 3 and 5 years after surgery were 79.1% and 74.8%, respectively, in the GNRI-high group, and 48.0% and 38.6% in the GNRI-low group. The GNRI was selected for the final multivariate analysis model for RFS. The GNRI was also found to affect the postoperative clinical course, including postoperative surgical complications and postoperative adjuvant chemotherapy. CONCLUSION: The GNRI may be a promising prognostic and predictive factor for gastric cancer. In the future, the GNRI may be used to select optimal treatment strategies.

Clinical Impact of Nutrition and Inflammation Assessment Tools in Pancreatic Cancer Treatment.

Perioperative adjuvant treatment and complete resection is the standard treatment for resectable pancreatic cancer and systemic chemotherapy is standard treatment for unresectable pancreatic cancer. To improve the survival of patients with pancreatic cancer, it is necessary to identify promising biomarkers to optimize the treatment. The availability of biomarkers may allow patients to receive a more aggressive or less toxic treatment. Recent studies showed that the inflammatory and nutritional status perioperatively and/or during chemotherapy affect short and long-term oncological outcomes in pancreatic cancer. Introduction of inflammatory and nutritional status evaluation in pancreatic cancer treatment might improve the postoperative surgical complications or chemotherapy-induced adverse events. However, to introduce these various nutritional and inflammation assessment tools in daily clinical practice, it is necessary to understand the characteristics of each nutrition and inflammation assessment tool. This review summarizes the background, current status, and future perspectives of nutrition and inflammation assessment tools in pancreatic cancer treatment.

Feasibility and Safety of Adjuvant Chemotherapy for Resected Colorectal Cancer in Patients With Renal Insufficiency: A Pooled Analysis of Individual Patient Data from Five Japanese Large-scale Clinical Trials.

BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

The clinical impacts of postoperative complications after colon cancer surgery for the clinical course of adjuvant treatment and survival.

AIM: We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan PATIENTS AND METHODS: The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group). RESULTS: A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively). CONCLUSION: POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

Usefulness of Nutrition and Inflammation Assessment Tools in Esophageal Cancer Treatment.

Multidisciplinary treatment for esophageal cancer leads to nutritional and inflammatory changes. Recent studies showed that nutritional and inflammatory changes during multidisciplinary treatment affect both short and long-term oncological outcomes in esophageal cancer treatment. Therefore, evaluation of the nutritional and inflammatory status during treatment is necessary in order to optimize and utilize multidisciplinary therapy for esophageal cancer. If patients with esophageal cancer are able to determine their nutritional and inflammatory status, they will be able to select the optimal esophageal cancer, anti-inflammation, and nutritional treatments. Various types of nutrition and inflammation assessment tools have been developed and reported for esophageal cancer, with each tool having its own clinical characteristics, which must be understood before being applied in clinical practice. This review summarizes the background, current status, and future perspectives on the application of nutrition and inflammation assessment tools in esophageal cancer treatment.

Clinical Course of Vitamin B12 Deficiency and Associated Risk Factors in Patients After Total Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Patients are at-risk for vitamin B12 deficiency after total gastrectomy due to a lack of intrinsic factors. The aim of the study was to clarify the clinical course and risk factors for vitamin B12 deficiency after total gastrectomy for gastric cancer patients. PATIENTS AND METHODS: Patients who underwent curative resection for gastric cancer were selected from the medical records of the Yokohama City University from 2000 to 2020. A logistic regression analysis was performed to identify risk factors for vitamin B12 deficiency. RESULTS: We evaluated 47 patients. The median serum vitamin B12 levels before surgery were 359 pg/ml, while those at 3, 6, 9, and 12 months after surgery these were 255 pg/ml, 197.5 pg/ml, 195 pg/ml, and 206 pg/ml, respectively. Univariate analyses to identify factors associated with vitamin B12 deficiency at 6 months after surgery showed that the occurrence of postoperative complications was a significant risk factor (OR=6.347, 95%CI=1.607-25.774, p=0.009), while adjuvant chemotherapy was a marginally significantly risk factor (OR=3.562, 95%CI=0.877-14.477, p=0.076). CONCLUSION: Almost half of the patients were diagnosed with vitamin B12 deficiency at 6 months after total gastrectomy for gastric cancer. In addition, the occurrence of postoperative complications and adjuvant chemotherapy were risk factors for vitamin B12 deficiency at 6 months after surgery.

Clinical Impact of Nutrition and Inflammation Assessment Tools in Gastric Cancer Treatment.

The standard treatment for gastric cancer is surgical resection and perioperative adjuvant treatment. Multidisciplinary treatment for gastric cancer leads to nutritional and inflammatory changes. Nutritional and inflammatory changes during multidisciplinary treatment can lead to poor physical activity, severe toxicity in patients receiving chemotherapy or radiation therapy, and poor oncological outcomes. Evaluation of the perioperative nutritional and inflammatory status during treatment is necessary in order to utilize and optimize multidisciplinary therapy for gastric cancer. If physicians were able to detect the perioperative nutritional and inflammatory status before and during gastric cancer treatment, they would be able to select the optimal treatment and perioperative nutritional treatment. Recently, various types of nutrition and inflammation assessment tools were developed and reported for gastric cancer. These nutrition and inflammation assessment tools have some clinical advantages, such as ease of implementation, perioperative accessibility, and low cost. On the other hand, each tool has its own clinical characteristics, which must be understood before using it in the clinical practice. This review summarizes the background, current status, and future perspectives on the application of nutrition and inflammation assessment tools in gastric cancer treatment.

The Albumin-Bilirubin Score Is a Prognostic Factor for Gastric Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: The albumin-bilirubin (ALBI) score is a promising tool for the evaluation of the perioperative hepatic function. The present study aimed to evaluate the clinical impact of the preoperative ALBI status in patients with gastric cancer (GC) who received curative treatment. PATIENTS AND METHODS: The present study included 244 patients who underwent curative treatment for GC between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7849. The 3- and 5-year OS rates were 87.3% and 80.9%, respectively, in the ALBI-low group, and 66.9% and 60.6% in the ALBI-high group; these differences were statistically significant (p<0.001). The ALBI score was included in the final multivariate analysis model [Hazard ratio (HR)=2.120, 95% confidence interval (CI)=1.177-3.818, p=0.012]. Similar results were observed for RFS. In addition, the ALBI score correlated with the introduction of postoperative adjuvant chemotherapy. CONCLUSION: The preoperative ALBI score correlated with both the OS and RFS of GC patients as well as the clinical course of adjuvant chemotherapy. Taken together, the ALBI score is a promising prognostic factor for GC.

Clinical Impact of Preoperative Albumin-Bilirubin Status in Esophageal Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: The albumin-bilirubin (ALBI) score, which evaluates the perioperative liver function, was developed, and had a clinical impact on both the short- and long-term oncological outcomes in some malignancies. We evaluated the clinical impact of preoperative albumin-bilirubin status in patients with resectable esophageal cancer who received curative treatment. PATIENTS AND METHODS: The study included 121 patients who underwent curative surgery followed by adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7. Eighty patients were classified into the ALBI-low group (ALBI score <-2.7), 41 patients were categorized into the ALBI-high group (ALBI score >-2.7). The 3- and 5-year OS rates were 62.2% and 53.2%, respectively, in the ALBI-low group, and 42.2% and 35.2% in the ALBI-high group. There was a significant difference in OS (p=0.0113). The 3- and 5-year RFS rates were 43.1% and 40.3%, respectively, in the ALBI-low group and 37.7% and 26.1% in the ALBI-high group. There was a significant difference in RFS (p=0.048). When comparing the perioperative clinical course between the ALBI-high and ALBI-low groups, the incidence of postoperative anastomotic leakage was 46.3% (19/41) in the ALBI-high group, and 27.5% (22/80) in the ALBI-low group (p=0.038). CONCLUSION: The ALBI status had a clinical impact on both OS and RFS in esophageal cancer patients. Therefore, ALBI may have potential application as a prognostic factor for esophageal cancer patients.

Effects of Goshajinkigan (TJ-107) for oxaliplatin-induced peripheral neurotoxicity using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire in a Phase II, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The aim of the present study was to evaluate the efficacy of TJ-107 for oxaliplatin-induced peripheral neurotoxicity in prospective, multi-institutional, randomized, double-blind, placebo-controlled Phase II trials using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire (FACT-GOG-NTX-12). PATIENTS AND METHODS: The patients who were registered to the Goshajinkigan oxaliplatin neurotoxicity evaluation study (UMIN000002211) were analyzed. A NTX-12 from the validated FACT/GOG-NTX-12 was assessed before treatment and at the end of every 2 cycles. RESULTS: The comparisons of the median scores for TJ-107 and the placebo at 8 and 26 weeks were as follows: numbness or tingling in the hands (P = 0.5820), numbness or tingling in the feet (P = 0.3236), feeling of discomfort in the hands (P = 0.8219), feeling of discomfort in the feet (P = 0.5361), joint pain or muscle cramps (P = 0.1974), feeling weak all over (P = 0.2771), trouble hearing (P = 0.2832), ringing or buzzing in ears (P = 0.1031), trouble buttoning buttons (P = 0.1653), trouble feeling the shape of small objects when held in hand (P = 0.2919), trouble walking (P = 0.5406), and pain in the hands or feet when exposed to cold temperatures (P = 0.1872). CONCLUSION: There might be no clinically significant difference between the use of TJ-107 and the severity and quality of life for patients treated with oxaliplatin.

Clinical Impact of Perioperative Oral Nutritional Treatment for Body Composition Changes in Gastrointestinal Cancer Treatment.

The standard treatment for gastrointestinal cancer is surgical resection and perioperative adjuvant treatment. Multidisciplinary treatment for gastrointestinal cancer leads to body composition changes. Body composition changes, such as skeletal muscle loss and body weight loss, during multidisciplinary treatment result in poor physical activity, severe toxicity of chemotherapy and/or radiation therapy, and poor oncological outcomes. Therefore, the hypothesis is that minimization of body composition changes during multidisciplinary treatment in gastrointestinal cancer patients, the continuation of postoperative adjuvant treatment in these patients might improve, thereby improving the oncological outcomes. Given this hypothesis, recent studies have focused on introducing perioperative oral nutritional treatment for gastrointestinal cancer patients. Thus far, oral nutritional treatment has proven promising and showed some clinical benefits for gastrointestinal cancer patients during the perioperative period. However, whether or not oral nutritional treatment has clinical benefits on the long-term oncological outcomes in gastrointestinal cancer remains unclear. To optimize oral nutritional treatment for gastrointestinal cancer patients, it is necessary to clarify the benefits of oral nutritional treatment on the long-term oncological outcomes in gastric cancer patients and establish the optimal approach to oral nutritional treatment.

Clinical Significance of Glioma-associated Oncogene 1 Expression in Patients With Locally Advanced Gastric Cancer Administered Adjuvant Chemotherapy With S-1 After Curative Surgery.

BACKGROUND/AIM: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. RESULTS: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. CONCLUSION: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

The clinical effect of Kampo medicine in multimodal treatment for Gastrointestinal Cancer in Japan.

Kampo medicine or Japanese/Chinese traditional herbal medicine has long been used for the treatment of various diseases, mainly in Asian countries. In recent years, Asian investigators have attempted to clarify the mechanism and clinical efficacy of Kampo medicine. This review summarizes the background, current status, and future perspectives of Kampo medicine in the multimodal treatment of gastrointestinal cancer. Regarding the clinical effect of Kampo medicine on postoperative dysfunction after gastrointestinal surgery, several investigators have reported that Daikenchuto (TJ-100) had clinical efficacy after abdominal digestive surgery. The administration of TJ-100 during the immediate postoperative period after esophageal cancer surgery, gastric cancer surgery, and liver cancer surgery appeared to promote early recovery of the postoperative bowel function. Regarding Kampo medicine for chemotherapy-induced adverse effects in gastrointestinal cancer, promising results have been obtained for Hangeshashinto (TJ-14) and Goshajinkigan (TJ-107). The addition of TJ-14 might be associated with an improvement in the duration of chemotherapy-induced oral mucositis, and the addition of TJ-107 might be associated with an improvement in oxaliplatin-induced peripheral neurotoxicity. However, while several clinical trials have shown the positive results of Kampo medication for gastrointestinal cancer treatment, the clinical effects of such medicines have been limited. Further trials to investigate the clinical benefits of Kampo medicine are needed.

[A Case of Sigmoid Colon Cancer Accompanied by Intestinal Malrotation Treated by Laparoscopic Surgery].

A 52-year-old man whose fecal occult blood test was positive was found to have type 2 sigmoid colon cancer by colonoscopy. On enhanced barium enema study, the cecum was in the pelvis, and the ascending colon was running medially in the abdomen. Enhanced CT scan of the abdomen revealed rotation of the superior mesenteric vein(SMV). We diagnosed the case as sigmoid colon cancer(cT3N0M0, StageⅡA)with non rotation-type intestinal malrotation, and performed laparoscopic surgery. We confirmed the small intestine to be located on the right side of the abdomen, the cecum to be located in the pelvis, and the ascending colon to be running medially in the abdomen. The ascending mesocolon was adherent to the right of the sigmoid mesocolon. Following dissections of the ascending mesocolon from the sigmoid mesocolon, we performed surgery via the inside approach as usual. We dissected the root of the inferior mesenteric artery(IMA), and the operation was completed. In laparoscopic surgery for colorectal cancer with intestinal malrotation, there are some reports that it could be performed safely if attention is paid to adhesion of the mesenteries and vascular variation in the course of preoperative imaging diagnosis. We report a case of laparoscopic surgery that could be safely performed for sigmoid colon cancer with non rotation-type intestinal malrotation.

Risk Factors for Peritoneal Recurrence in Stage II to III Colon Cancer.

BACKGROUND: Most previous reports to analyze risk factors for peritoneal recurrence in patients with colon cancer have been observational studies of a population-based cohort. OBJECTIVE: This study aimed to determine the risk factors for peritoneal recurrence in patients with stage II to III colon cancer who underwent curative resection. DESIGN: This was a pooled analysis using a combined database obtained from 3 large phase III randomized trials (N = 3714). SETTINGS: Individual patient data were collected from the Japanese Foundation for Multidisciplinary Treatment of Cancer clinical trials 7, 15, and 33, which evaluated the benefits of postoperative 5-fluorouracil-based adjuvant therapies in patients with locally advanced colorectal cancer. PATIENTS: We included patients who had stage II to III colon cancer and underwent curative resection with over D2 lymph node dissection. MAIN OUTCOME MEASURES: Main outcomes measured were risk factors for peritoneal recurrence without other organ metastasis after curative surgery. RESULTS: Peritoneal recurrence occurred in 2.3% (86/3714) of all patients undergoing curative resection. Mean duration from operation to peritoneal recurrence was 17.0 ± 10.3 months. Of these patients with peritoneal recurrence, 29 patients (34%) had recurrence in ≥1 other organ. Multivariate analysis showed that age (≥60 y: HR = 0.531; p = 0.0182), pathological T4 (HR = 3.802; p < 0.0001), lymph node involvement (HR = 3.491; p = 0.0002), and lymphadenectomy (D2: HR = 1.801; p = 0.0356) were independent predictors of peritoneal recurrence. The overall survival was lower in patients who developed peritoneal recurrence than in those with other recurrence (HR = 1.594; p = 0.002). LIMITATIONS: The regimens of adjuvant chemotherapy were limited to oral 5-fluorouracil. CONCLUSIONS: Our findings clarified the risk factors for peritoneal recurrence in patients who underwent curative resection for colon cancer. See Video Abstract at http://links.lww.com/DCR/A609.

Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal and lung malignancy patients.

The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078-1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis.

BACKGROUND AND AIMS: Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are widely recognized to have beneficial effects against cardiovascular disease. We investigated the association of n-3 PUFAs levels with carotid atherosclerosis in patients on hemodialysis (HD), who are at high risk for cardiovascular events. METHODS: Carotid ultra-sound was performed in a total of 461 patients on HD (male 67%, age 67 ± 12years, diabetes rate 46%). Intima-media thickness (IMT) and the plaque score (PS) in carotid arteries were measured. Carotid atherosclerosis was defined as IMT >1.2 mm and/or PS > 5.0. The levels of n-6 PUFAs [dihomo-gamma-linolenic acid (DHLA) and arachidonic acid (AA)] and n-3 PUFAs [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] were also measured prior to carotid ultra-sound. RESULTS: Carotid atherosclerosis was observed in 94 patients (20.4%). Individual PUFAs levels were comparable between patients with and without carotid atherosclerosis. However, the ratio of EPA/AA and that of n-3/n-6 PUFAs were significantly lower in patients with carotid atherosclerosis compared to those without (median 0.36 vs. 0.41, p = 0.031 and 0.85 vs. 0.93, p = 0.041, respectively]. After adjustment for other confounders, the ratio of EPA/AA (OR 0.30, 95% CI 0.12-0.70, p = 0.0055) and the ratio of n-3/n-6 PUFAs (OR 0.45, 95% CI 0.25-0.80, p = 0.0066) showed an independent reverse association with carotid atherosclerosis. In addition, the area under receiver-operating characteristic curves for carotid atherosclerosis was significantly greater in an established risk model with EPA/AA and n-3/n-6 ratios than in the established risk model alone. CONCLUSIONS: These data suggest that low ratios of both EPA/AA ratio and n-3/n-6 PUFAs were closely associated with carotid atherosclerosis in patients on HD.

Double-blind, placebo-controlled, randomized phase II study of TJ-14 (Hangeshashinto) for infusional fluorinated-pyrimidine-based colorectal cancer chemotherapy-induced oral mucositis.

PURPOSE: Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a double-blind, placebo-controlled, randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with colorectal cancer. METHODS: Ninety-three patients with colorectal cancer who developed moderate-to-severe COM (WHO grade ≧1) during any cycle of chemotherapy using FOLFOX, FOLFIRI, and/or XELOX treatment were randomly assigned to receive either TJ-14 (n = 46) or placebo (n = 47). Patients received the administration of placebo or TJ-14 for 2 weeks at the start of the next course of chemotherapy. Patients were assessed three times per week for safety and for COM incidence and its severity using the WHO grading. RESULTS: Ninety eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were included in the analysis after the key-opening. Although the incidence of grade ≧2 oral mucositis was lower for patients treated with TJ-14 compared to those treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p = 0.41). The median duration of grade ≧2 mucositis was 5.5 versus 10.5 days (p = 0.018). No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration. CONCLUSION: The present study results did not meet the primary endpoint. However, TJ-14 demonstrated a significant effect in the treatment of grade ≧2 mucositis in patients with colorectal cancer compared to the placebo.