Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Administration Method of Adjuvant Tegafur-Uracil and Leucovorin Calcium in Patients with Resected Colorectal Cancer: A Phase III Study.

LESSONS LEARNED: The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy. BACKGROUND: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. METHODS: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival. RESULTS: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). CONCLUSION: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.

Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific Atg7-deficient mice (Villin-cre; Atg7f/f and LysM-cre; Atg7f/f mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in Villin-cre; Atg7f/f mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix4) did not suppressed colitis in LysM-cre; Atg7f/f mice. In large intestinal macrophages (Mφ) of Atg7f/f mice, SO and Mix4 upregulated the expression of marker genes of anti-inflammatory Mφ including Arg1, Cd206, and Relma. However, these alterations were not induced in LysM-cre; Atg7f/f mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal Mφ with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.

Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA.

Halogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH-[Formula: see text], lone pair (LP)-[Formula: see text], and [Formula: see text]-[Formula: see text] interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.

Postoperative XELOX therapy for patients with curatively resected high-risk stage II and stage III rectal cancer without preoperative chemoradiation: a prospective, multicenter, open-label, single-arm phase II study.

BACKGROUND: Preoperative 5-FU-based chemoradiation is currently a standard treatment for advanced rectal cancer, particularly in Western countries. Although it reduced the local recurrence, it could not necessarily improve overall survival. Furthermore, it can also produce adverse effects and long-term sphincter function deficiency. Adjuvant oxaliplatin plus capecitabine (XELOX) is a recommended regimen for patients with curatively resected colon cancer. However, the efficacy of postoperative adjuvant therapy for rectal cancer patients who have not undergone preoperative chemoradiation remains unknown. We aimed to evaluate the efficacy of surgery and postoperative XELOX without preoperative chemoradiation for treating rectal cancer. METHODS: We performed a prospective, multicenter, open-label, single arm phase II study. Patients with curatively resected high-risk stage II and stage III rectal cancer who had not undergone preoperative therapy were treated with a 120 min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and capecitabine (2000 mg/m2/day) in 2 divided doses for 14 days of a 3-week cycle, for a total of 8 cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: Between August 2012 and June 2015, 60 men and 47 women with a median age was 63 years (range: 29-77 years) were enrolled. Ninety-three patients had Eastern Cooperative Oncology Group performance status scores of '0' and 14 had scores of '1'. Tumors were located in the upper and lower rectums in 54 and 48 patients, respectively; 8 patients had stage II disease and 99 had stage III. The 3-year DFS was 70.1% (95% confidence interval, 60.8-78.0%) and 33 patients (31%) experienced recurrence, most commonly in the lung (16 patients) followed by local recurrence (9) and hepatic recurrence (7). CONCLUSIONS: Postoperative XELOX without preoperative chemoradiation is effective for rectal cancer and provides adequate 3-year DFS prospects. TRIAL REGISTRATION: This clinical trial was registered in the University Hospital Medical Information Network registry system as UMIN000008634 at Aug 06, 2012.

[Long-Term Survival with Multidisciplinary Treatment and Nutritional Therapy for Thoracic Esophageal Cancer with Multiple Liver Metastases-A Case Report].

The patient was a 63-year-old man with a chief complaint. Upper endoscopic examination revealed a semicircular type 2 lesion, sized 24-28 cm, on the incisor teeth and a 3 cm sized elevated lesion directly above the EGJ. When biopsy was performed, squamous cell carcinoma(SCC)was detected. In this case, lymph node metastasis and multiple liver metastases were observed, and diagnosis at the first examination was cT3N2M1(HEP), Stage Ⅳ. After 7 months of chemotherapy, he underwent right thoracic esophageal subtotal resection, 3-field lymph node dissection, posterior mediastinal gastric tube reconstruction, and partial hepatectomy. Despite receiving postoperative chemotherapy, he showed recurrence in the liver(S8). Four additional courses of chemotherapy were administered and partial hepatectomy(S8)was performed, without the appearance of new lesions. He was considered to be cured 1 year and 6months after starting the treatment and was followed- up without chemotherapy. However, 4 months later, chemotherapy was resumed when right adrenal and abdominal wall metastases and liver recurrence(S3)were found. After that, the regimen was modified, and he continued treatment. More than 4 years have passed since the start of treatment, but the treatment has been continued without a decline in ADL.

Perioperative Nutritional Support With Beta-hydroxy-beta-methylbutyrate, Arginine, and Glutamine in Surgery for Abdominal Malignancies.

Although beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) may contribute to wound healing, no prospective studies have investigated the efficacy of a compound consisting of HMB, Arg, and Gln (HMB/Arg/Gln) for reducing wound complications following open abdominal surgery. OBJECTIVE: This study evaluates the usefulness of perioperative nutrition using HMB/Arg/Gln in patients who were scheduled to undergo open surgery for abdominal malignancies in a randomized controlled trial. MATERIALS AND METHODS: Patients scheduled for open surgery for abdominal malignancies were randomized to receive HMB/Arg/Gln (1.2 g HMB, 7 g L-Arg, and 7 g L-Gln) or placebo (isocaloric juice). The supplements were provided once daily for 3 days preoperatively and once daily for 7 days postoperatively. The primary endpoint was the incidence of wound complications. Secondary endpoints included the incidence of other complications, postoperative duration of hospital stay, total-body skeletal muscle mass, handgrip strength, and skin water content. RESULTS: Sixty-one patients were randomly assigned to either the HMB/Arg/Gln (n = 31) or the placebo (n = 30) group. One patient in the HMB/Arg/Gln group was ineligible because laparoscopic surgery was performed; thus, 60 patients were analyzed. The incidence of wound complications (20%) was the same in both groups (P = 1.000). There were no significant differences in the incidence of other complications, body composition, handgrip strength, or skin water content between the 2 groups. Serum growth hormone (GH) levels were significantly higher for patients whose total intake was > 80% of planned volume in the HMB/Arg/Gln group. CONCLUSIONS: The incidence of wound complications would not be reduced by perioperative HMB/Arg/Gln administration in patients who underwent open surgery. The efficacy of HMB/Arg/Gln for increasing serum GH levels needs to be validated in another large-scale randomized controlled trial.

Association of iron metabolic enzyme hepcidin expression levels with the prognosis of patients with pancreatic cancer.

Hepcidin and ferroportin, which are known as key iron regulators, may be used in future treatments of pancreatic ductal adenocarcinoma. Iron is essential for life support; it helps oxygen molecules bind to hemoglobin and acts as an important catalytic enzyme center. However, iron overload is a risk factor for cancer, possibly through the generation of reactive oxygen species (ROS). Hepcidin, which is a peptide hormone mainly generated by the liver, inhibits iron absorption via enterocytes and iron release from macrophages. Notably, hepcidin regulates iron homeostasis in the body by regulating the iron transporter ferroportin. In the present study, it was assumed that high hepcidin expression and low ferroportin expression result in malignancy. Therefore, it was examined whether hepcidin and ferroportin expression levels were correlated with the prognosis of pancreatic cancer in patients. Results revealed that high hepcidin expression levels and low ferroportin expression levels in pancreatic cancer tissue were significantly associated with poor prognosis in the analyses of overall survival (P=0.0140 and 0.0478, respectively). Additionally, there was no significant difference in disease-free survival in the hepcidin- and ferroportin-staining groups. Hepcidin expression correlated with the pathological stage and vascular invasion (P=0.0493 and 0.0400, respectively), and ferroportin expression was correlated with age (P=0.0372). Multivariate analysis of overall survival in the hepcidin-staining group revealed that pathological N factor (pN), adjuvant chemotherapy, and hepcidin expression were independent prognostic factors (P=0.0450, 0.0002, and 0.0049, respectively). Similarly, multivariate analysis of overall survival in the ferroportin-staining group revealed that vascular invasion, and ferroportin expression were independent prognostic factors (P=0.0028, P<0.0001, and P=0.0056, respectively). Thus, hepcidin and ferroportin expressions might be novel prognostic indicators for pancreatic cancer.

Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation Therapy.

BACKGROUND: The cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDAC) are well known to play a dominant role in distant metastasis. Nevertheless, the effect on CAFs with current chemoradiation therapies remains uncertain. OBJECTIVE: This study aimed to reveal the role of CAFs under current chemoradiation therapy (CRT) and investigate the factors regulating CAFs. METHODS: α-SMA-positive cells in 86 resected PDAC specimens with/without preoperative CRT were evaluated by immunohistochemistry. Various factors, including the plasma levels of vitamin D, were investigated for association with the number of CAFs or distant metastasis-free survival (DMFS). Human pancreatic satellite cells (hPSCs) extracted from clinical specimens were used to validate the factors. RESULTS: All PDAC samples contained CAFs but the number varied widely. Multivariate analysis for DMFS indicated a larger number of CAFs was a significant risk factor. Univariate analysis for the number of CAFs identified two clinical factors: preoperative CRT and lower plasma levels of vitamin D. In subgroup analysis, the higher plasma level of vitamin D was a dominant factor for longer DMFS in PDAC patients after preoperative CRT. These results were validated by using extracted hPSCs. Irradiation activated stromal cells into CAFs facilitating malignant characteristics of PDAC and the change was inhibited by vitamin D supplementation in vitro. CONCLUSION: In conjunction with established current therapies, vitamin D supplementation may be an effective treatment for PDAC patients by inactivating CAFs.

Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG).

PURPOSE: Oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) is not inferior to standard weekly fluorouracil and folinate for stage II/III colon cancer. However, protein-bound polysaccharide K (PSK) has been evaluated as postoperative adjuvant therapy for colorectal cancer. This report is the first of MCSGO-CCTG, which compared UFT/LV to UFT/PSK as adjuvant chemotherapy for stage IIB or III colorectal cancer in patients who had undergone Japanese D2/D3 lymph node dissection. METHODS: The primary endpoint was the 3-year disease-free survival (DFS). A randomized non-inferiority study compared UFT/LV to UFT/PSK. The overall survival, adverse events, compliance, and quality of life were also investigated as the secondary endpoints. RESULTS: Between March 2006 and December 2010, 357 patients were randomized to UFT/PSK (n = 178) or UFT/LV (n = 179) (median age 65 years, colon/rectum 67.4/32.6%, stage IIB/IIIA/IIIB/IIIC 11.1/15.7/55.0/18.2%). The 3-year DFS rate was 82.3% in those receiving UFT/LV and 72.1% in those receiving UFT/PSK. The non-inferiority of UFT/PSK adjuvant therapy to UFT/LV therapy was not verified (-9.06%, 90% confidence interval -17.06 to -1.06%). The 3-year overall survival rate was 95.4% in those receiving UFT/LV and 90.7% in those receiving UFT/PSK. CONCLUSIONS: As adjuvant chemotherapy for stage IIB and III colorectal cancer patients, UFT/PSK adjuvant therapy was not non-inferior to UFT/LV therapy with respect to the DFS.

Patients Treated with Preoperative Chemoradiation for Pancreatic Ductal Adenocarcinoma have Impaired Bone Density, a Predictor of Distant Metastasis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm that spreads to surrounding tissue or distant sites. This study investigated distant metastases in PDAC patients with or without preoperative chemoradiation therapy (CRT), focusing on vitamin D levels and bone density. METHODS: This study included 146 patients with PDAC who underwent surgery from 2007 to 2014. Bone density was evaluated using computed tomography, and the preoperative vitamin D level was calculated by enzyme-linked immunosorbent assay (ELISA) for patients with available plasma (48 cases). RESULTS: When the patients were divided into two groups according to the change in bone density, the group with decreased bone density had a shorter distant metastasis-free survival time (DMFS) after surgery than the other group (p < 0.05). Low vitamin D was a weak predictor of DMFS, but the difference was not significant (p = 0.08), perhaps because of the sample size. Multivariate analysis indicated three significant factors associated with distant metastasis: a decrease in bone density (hazard ratio [HR], 2.17; p = 0.04), normalization of the Dupan-2 value after surgery (hazard ratio [HR], 0.39; p = 0.02), and completion of adjuvant chemotherapy (HR, 0.29; p < 0.01). Univariate analysis showed that a low vitamin D concentration (<20 pg/ml) was a risk factor (p = 0.04) for bone density change. Multivariate analysis found that preoperative CRT was the only factor associated (±, OR, 5.8; p = 0.04) with bone density change, suggesting that preoperative CRT significantly decreases bone density in patients with insufficient vitamin D. CONCLUSION: Patients treated with preoperative CRT tend to have impaired bone density, which is a predictor of distant metastasis. Thus, vitamin D supplementation may decrease distant metastasis.

Interim analysis of a phase II trial evaluating the safety and efficacy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer.

PURPOSE: Adjuvant oxaliplatin plus oral capecitabine (XELOX) is recommended for patients with curatively resected colon cancer. However, its safety and tolerability in Asian patients is unclear; therefore, we evaluated the safety and efficacy of adjuvant XELOX in Japanese patients with curatively resected stage III colon cancer (MCSCO-1024) and present the interim safety data. METHODS: This prospective, multi-center, open-label, single-arm phase II study recruited patients with curatively resected stage III colon cancer. The protocol was a 120-min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and oral capecitabine (2000 mg/m2/day) in two divided doses for 14 days of a 3-week cycle, for a total of eight cycles (24 weeks). The primary endpoint was the 3-year disease-free survival, and secondary endpoints were the treatment completion rate, safety profile (rate and severity of adverse events), and correlation of adverse events, such as peripheral sensory neuropathy (PSN), with the administration period of oxaliplatin, etc. RESULTS: From November 2011 to August 2014 (34 months), 196 patients were enrolled. Safety was analyzed in 190 patients. The median total doses of capecitabine and oxaliplatin were 215,586.9 and 777.2 mg/m2, respectively, while the median relative dose intensities were 82.5 and 76.0%, respectively. The overall treatment completion rate was 73.7%. The most frequent treatment-related adverse event was PSN (88.4%), while the most frequent grade ≥3 treatment-related adverse events were neutropenia (12.6%), PSN (6.3%), diarrhea (4.2%), and thrombocytopenia (4.2%). There were no treatment-related deaths. CONCLUSIONS: Adjuvant XELOX is tolerable for Japanese patients with Stage III colon cancer.

Randomized Controlled Trial of Adjuvant Chemotherapy with Fluoropyrimidines Versus Surgery-alone for Gastric Cancer.

AIM: This prospective randomized study compared the survival of patients with stage IB-IIIA gastric cancer treated with surgery alone or surgery followed by adjuvant chemotherapy. PATIENTS AND METHODS: Patients with pathological stage IB-IIIA disease were randomly assigned to the following groups: surgery alone (n=116), or surgery followed by adjuvant chemotherapy with 5-fluorouracil, doxifluridine, or uracil-tegafur for 12 months (n=113). RESULTS: The overall survival rate was 86.1% in the adjuvant group and 78.5% in the surgery-alone group. The overall survival rate did not significantly differ between the adjuvant-chemotherapy and surgery-only groups (p=0.163). In the subgroup analyses, patients with stage II disease and those receiving uracil-tegafur treatment in the adjuvant group showed significantly better prognosis than those in the surgery-alone group (p=0.036 and 0.005, respectively). CONCLUSION: This study did not find a significant survival benefit to be associated with adjuvant chemotherapy with fluoropyrimidines in patients with stage IB-IIIA gastric cancer. However, it may be effective for patients with stage II disease. Additionally, uracil-tegafur is a promising agent for adjuvant chemotherapy of gastric cancer if S-1 is not available because of its toxicity.

The basal nutritional state of PDAC patients is the dominant factor for completing adjuvant chemotherapy.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and several clinical trials have shown that adjuvant chemotherapy after curative resection can improve the prognosis of these patients. However, the adjuvant chemotherapy completion rate is less than satisfactory. If this rate could be increased then the overall prognosis of PDAC might be improved; however, reports addressing this problem are insufficient. To elucidate the factors, we retrospectively investigated PDAC patients. METHODS: Various factors of 121 PDAC patients undergoing R0 resection, including preoperatively treated patients, were investigated. Univariate and multivariate analyses were performed to investigate the factors that were associated with the completion of adjuvant chemotherapy. RESULTS: The analysis identified age and the prognostic nutritional index (PNI) as significant independent factors. A receiver operating characteristic curve analysis of age yielded a cutoff value of 67 years (sensitivity, 64%; specificity, 78%). Univariate and multivariate analyses of the 61 patients who were over 67 years of age revealed that the PNI (odds ratio, 0.85; P = 0.048) and Evans grade (odds ratio, 0.041; P = 0.0010) were significant factors for the completion of chemotherapy. CONCLUSIONS: The results of our investigation suggest that nutrition should be controlled in older PDAC patients to facilitate the completion of adjuvant chemotherapy.

ω-3 Fatty Acids Reduce Chemotherapy-Induced Hematological Toxicity by Bone Marrow Stimulation in Mice.

BACKGROUND: ω-3 Fatty acids exert several benefits during chemotherapy, such as preventing intestinal mucosal damage and improving response to chemotherapy. However, little is known about the effect of ω-3 fatty acids on chemotherapy-induced hematological toxicities. METHODS: Mice that had consumed either an ω-3-rich or an ω-3-poor diet for 2 weeks were intraperitoneally administered cisplatin. The resultant changes in blood cell count, bone marrow cell count, and cytokine levels in bone marrow supernatant were analyzed. The effect of ω-3 fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to cisplatin was also examined. RESULTS: Although peripheral blood cell counts decreased after cisplatin treatment in both groups of mice, the decrease in white blood cell count was significantly lower in mice that consumed the ω-3-rich diet. The decrease in bone marrow cells after cisplatin treatment was also reduced in mice that consumed the ω-3-rich diet. Levels of stem cell factor (SCF) and fibroblast growth factor 1 (FGF-1) were significantly higher in bone marrow supernatants from mice that consumed the ω-3-rich diet. The rate of apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing ω-3 fatty acids was significantly lower than in PBMCs cultured in control medium. CONCLUSION: ω-3-Rich diets reduced chemotherapy-induced leukopenia in mice. This may be the result of increased numbers of bone marrow cells due to higher levels of SCF and FGF-1 in the bone marrow.

Randomized study of the clinical effects of ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

OBJECTIVES: Omega-3 (ω-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. METHODS: Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received ω-3-rich enteral nutrition (EN; n = 31) or ω-3-poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of ω-3 fatty acids was 900 mg in the ω-3-rich group and 250 mg in the ω-3-poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers. RESULTS: The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the ω-3-rich group, than in the ω-3-poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the ω-3-rich group than in the ω-3-poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the ω-3-rich group than in the ω-3-poor group (P = 0.012 and P = 0.015, respectively). CONCLUSIONS: ω-3-rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the ω-3-poor EN support.

Micrometastasis Volume in Lymph Nodes Determines Disease Recurrence Rate of Stage II Colorectal Cancer: A Prospective Multicenter Trial.

PURPOSE: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. EXPERIMENTAL DESIGN: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. RESULTS: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016). CONCLUSIONS: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201-8. ©2016 AACR.

[Recurrence of Jejunal Carcinoma in the Ileum and Ovary - A Case Report].

Small bowel carcinoma has poor prognosis. The basis of treatment is surgical resection. There are no established guidelines for chemotherapy. We report a case in which we performed surgical resection of recurrent jejunal carcinoma. A 62-year-old woman underwent laparoscopic partial resection of the small intestine for primary jejunal carcinoma. The final diagnosis was T3N0M0, fStage II A. After 16 months of follow-up, she developed abdominal pain and vomiting. We diagnosed recurrence of jejunal carcinoma in the ileum and right ovary. Single-port laparoscopic small intestinal resection and right ovariectomy were performed. The patient underwent curative resection for recurrent lesions. The type of tumor in the ileum and right ovary was consistent with primary jejunal carcinoma by histopathological examination, and was diagnosed as recurrence of jejunal carcinoma. She is now on adjuvant chemotherapy with XELOX.

[A Case of Concurrent Cancer in a Giant Rectal Villous Adenoma That Resulted in Extensive Lymph Node Metastases].

The patient was a 72-year-old man. Colonoscopy revealed a circumferential villous tumor with granular aggregates extending from the rectosigmoid (RS) to the lower rectum (Rb). Although most portions were indicative of a villous adenoma, a reddish coarse region at the upper rectum (Ra) was diagnosed as a concurrent adenocarcinoma based on biopsies. Consequently, we performed laparoscopy-assisted intersphincteric resection (ISR) and D3 lymph node dissection. Pathological diagnosis revealed multiple lymph node (LN) metastases, including ones at the root of the inferior mesenteric artery (IMA). Adjuvant chemotherapy was administered with XELOX. However, computed tomography (CT) and positron emission tomography (PET) conducted 6 months after surgery revealed recurrent LN metastasis in the mesosigmoid ie, extra-regional LN metastasis. Therefore, chemotherapy was reinitiated with a FOLFIRI-based regimen. Metastases were observed in the lateral LNs and the para-aortic LNs 9 months after surgery, and in the left supraclavicular LNs 12 months after surgery. Herein, we report a rare case of cancer concurrent with a giant villous adenoma, which resulted in extensive LN metastases.

[Adjuvant treatment for esophagogastric junction cancer].

Conducting clinical trials to establish evidence of the benefits of adjuvant treatment for resectable esophagogastric junction (EGJ) cancer is difficult because it is a very rare disease compared with gastric or esophageal cancer. In the West, where esophageal cancer occurs more frequently than gastric cancer, a phase III trial (the CROSS trial) demonstrated the efficacy of preoperative chemoradiotherapy using carboplatin plus paclitaxel for patients with esophageal or EGJ cancer. Thus, this preoperative regimen is considered to be the standard adjuvant treatment for resectable EGJ cancer in the West. On the other hand, the Western evidence is not widely accepted in Asia because there are many differences in surgical techniques, particularly in the field of lymph node dissection, between the West and Asia. The standard adjuvant treatment for resectable EGJ cancer in Asia is postoperative chemotherapy using S-1 alone or capecitabine plus oxaliplatin based on the results of two large-scale phase III trials in gastric cancer conducted in East Asia. The incidence of EGJ cancer has recently increased in Japan, and nationwide studies to develop more effective adjuvant treatment for resectable EGJ cancer should be conducted in the near future.