Controlling Nutritional Status Score Serves as a Prognosticator in Esophageal Squamous Cell Carcinoma: Optimal Timing of Evaluation of Patients Undergoing Neoadjuvant Treatment.

BACKGROUND: Usefulness of various nutritional indices for management of patients with esophageal squamous cell carcinoma (ESCC) has been reported. Although Controlling Nutritional Status (CONUT) score is among promising indices to predict outcome, the optimal timing for its measurement during the perioperative period remains unknown. Here the prognostic value of the CONUT score was assessed among patients with ESCC. METHODS: We analyzed 464 patients who underwent subtotal esophagectomy of ESCC, of which 276 patients were treated with neoadjuvant treatment (NAT). The significance of the associations between candidate parameters including the CONUT score and postoperative prognosis were evaluated. RESULT: Among the 25 candidate predictors, the preoperative CONUT score had the highest correlation with overall survival (OS) after surgery. Patients were categorized as follows: normal, mild, and moderate or severe, on the basis of the preoperative CONUT score. OS was significantly shortened as the CONUT score worsened. Multivariable analysis revealed that the CONUT scores of the subgroups mild (Hazard ratio [HR] 1.69) and moderate or severe (HR 2.18) were independent predictors of poor prognosis for OS. Furthermore, in an analysis limited to patients who underwent NAT, OS was significantly shortened as the preoperative CONUT score worsened. On the contrary, there was no significant difference in RFS among patient groups stratified by the CONUT score determined before NAT. CONCLUSIONS: Our study indicates that the preoperative CONUT score serves as a prognosticator in resectable ESCC. The preoperative CONUT value was more useful than that before NAT in patients administered NAT.

A prospective trial to evaluate treatment effects of a ß-hydroxy-ß-methylbutyrate containing nutrient for leakage at the anastomotic site after esophagectomy.

Anastomotic leakage after esophagectomy is associated with prolonged hospitalization and increased medical cost. Additionally, it sometimes leads to a fatal condition and impaired postoperative quality of life. During the process of wound healing, ß-hydroxy-ß-methylbutyrate (HMB) is important for collagen biosynthesis. An open-label prospective intervention trial has been designed to evaluate the treatment effect of an enteral nutrient containing HMB with arginine and glutamine (Abound, Abbott Japan Co., Ltd.) for leakage at the anastomotic site after esophagectomy. Patients in whom leakage at the anastomotic site developed within 14 days after esophagectomy are eligible and Abound (24 g) is administered for 14 days through an enteral feeding tube. The target sample size is 10. The primary endpoint is duration between diagnosis and cure of leakage. Surgical procedure, safety, length of fasting, drainage placement and hospital stay, and nutritional status are determined as secondary endpoints. A historical control consisting of 20 patients who had leakage at the anastomotic site after esophagectomy between 2005 and 2018 at Nagoya University Hospital is compared with enrolled patients.

Biological and conditional factors should be included when defining criteria for resectability for patients with pancreatic cancer.

BACKGROUND: This study aimed to evaluate novel resectability criteria for pancreatic ductal adenocarcinoma (PDAC) proposed by the International Association of Pancreatology (IAP) by comparing them with the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: 369 patients who underwent upfront surgery for PDAC were retrospectively analyzed. Overall survival (OS) of each group as defined by either of the guidelines were compared and preoperative prognostic factors for OS were identified. RESULTS: Based on the IAP-criteria, 157 patients were classified as resectable (R), 192 as borderline resectable (BR) and 20 as unresectable (UR), with the median survival time (MST) of 40 months, 17 and 11, respectively. In contrast to the NCCN-criteria, BR demonstrated significantly better OS than UR (P = 0.023) under the IAP-criteria. Performance status ≥2 (hazard ratio [HR]: 2.47, P = 0.014) and lymph node metastasis suspected by imaging (HR: 1.55, P = 0.003) were identified as independent prognostic factors by the multivariate analysis along with portal or arterial invasion, while carbohydrate antigen 19-9 ≥ 500 U/ml was not (HR: 1.23, P = 0.190). CONCLUSION: The IAP-criteria, which includes biological and conditional factors, resulted in superior separation of survival curves stratified by the resectablity when compared with the NCCN-criteria.

Clinical Impact of Neoadjuvant Therapy on Nutritional Status in Pancreatic Cancer.

BACKGROUND: The association between neoadjuvant therapy (NAT) and nutritional status in pancreatic cancer (PC) is unknown. OBJECTIVE: The aim of this study was to assess the impact of NAT on nutritional status. METHODS: Overall, 161 patients who underwent pancreatoduodenectomy for PC between August 2010 and March 2017 were enrolled and were divided into two groups: the neoadjuvant group (NAG; n = 67) and the control group (CG; n = 94). Based on relative dose intensity (RDI), patients in the NAG group were further divided into RDI ≥ 80% (n = 39) and RDI < 80% (n = 19). Changes in nutritional index, inflammatory index, and inflammation-based prognostic scores during NAT and the perioperative period were assessed. RESULTS: Retinol-binding protein, prealbumin, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutrition index significantly worsened in the NAG after NAT (p = 0.007, p = 0.03, p = 0.04, p = 0.007, and p = 0.004, respectively). The recovery of rapid turnover proteins after postoperative day 5 was significantly worse in the NAG compared with the CG (p < 0.05), but tended to be more prompt in the RDI ≥ 80% group among the NAG. There was no significant difference in the incidence of postoperative complications, length of hospital stay, and time to postoperative adjuvant therapy between the NAG and the CG. CONCLUSIONS: NAT for PC could aggravate nutritional status and hamper its postoperative recovery. Furthermore, malnutrition might decrease tolerance of NAT. These findings suggest the importance of nutritional support for patients with NAT in PC.

Preoperative Albumin-Bilirubin Grade Predicts Recurrences After Radical Gastrectomy in Patients with pT2-4 Gastric Cancer.

BACKGROUND: The albumin-bilirubin (ALBI) score was initially developed for assessing liver dysfunction severity and was suggested to have prognostic value in patients with hepatocellular carcinoma. We aimed to evaluate the prognostic impact of ALBI grade in patients with advanced gastric cancer (GC) after radical gastrectomy. METHODS: This study included 283 patients who underwent radical gastrectomy for pT2-4 GC without preoperative treatment. ALBI was calculated as follows: (log10 bilirubin (µmol/L) × 0.66) + (albumin (g/L) × -0.0852) and categorized into grades 1 (≤-2.60), 2 (-2.60<, ≤-1.39) and 3 (-1.39<). RESULTS: The median ALBI score was -2.96, and a number of patients in ALBI grades 1, 2 and 3 were 228, 55 and 0, respectively. Patients with ALBI grade 2 had a lower administration rate of adjuvant chemotherapy than those with ALBI grade 1, whereas no significant differences were found in morbidity rate and disease stage. The ALBI grade 2 group was more likely to have shorter disease-specific and disease-free survival compared with the ALBI grade 1 group. Multivariable analysis identified ALBI grade 2 as an independent prognostic factor for disease-free survival (hazard ratio 1.97, 95% confidence interval 1.10-3.47, p = 0.0242). Survival differences between ALBI grade 1 and 2 groups were increased in the patient subset that received adjuvant chemotherapy. ALBI grade 2 was correlated with a shortened duration of administration of postoperative S-1 adjuvant. CONCLUSIONS: ALBI grade serves as a simple and promising predictive factor for disease-free and disease-specific survival in patients with pT2-4 GC after radical gastrectomy.

Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer.

OBJECTIVE: To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). BACKGROUND: Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. METHODS: We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. RESULTS: Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. CONCLUSIONS: SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC.

Evaluation and proposal of novel resectability criteria for pancreatic cancer established by the Japan Pancreas Society.

BACKGROUND: The guidelines for the classification of the resectability of pancreatic cancer established by the National Comprehensive Cancer Network can be difficult to utilize in clinical practice. We evaluated novel criteria proposed by the Japan Pancreas Society. METHODS: We analyzed 382 patients with pancreatic cancer between 2001 and 2015 for survival differences among subgroups classified according to the Japan Pancreas Society classification. Overall survival and disease-free survival were expressed as median values and compared with data based on the National Comprehensive Cancer Network classification, and differences in initial patterns of recurrence were analyzed. RESULTS: Overall survival times according to the Japan Pancreas Society criteria were 34.2, 29.7, 17.3, 14.3, and 15.8 months for the groups defined as resectable, resectable with portal vein invasion, borderline resectable with portal vein invasion, borderline resectable with arterial invasion, and unresectable by locally advanced disease respectively. The overall survival of the resectable group was better than those of the borderline resectable with portal vein invasion or borderline resectable with arterial invasion groups (P < .0001); however, the borderline resectable with portal vein invasion, borderline resectable with arterial invasion, and unresectable by locally advanced groups showed no differences in overall survival. The resectable group showed a tendency toward better survival than the resectable with portal vein invasion group (P = .058). The median overall survival times according to the classic 2012 National Comprehensive Cancer Network criteria were 30.5, 20.5, 15.8, and 13.8 months for the resectable, portal invasion, common hepatic artery and superior mesenteric artery invasion groups, respectively. Each survival curve was clearly separate. The borderline resectable with arterial invasion and unresectable by locally advanced groups exhibited high local recurrence rates (42.0% and 44.8%, respectively). CONCLUSION: The Japan Pancreas Society criteria, which are simpler, predicted survival differences between the resectable group and the other subgroups. Our data suggest that cancer patients with borderline resectable pancreatic cancer (borderline resectable with portal vein invasion and borderline resectable with arterial invasion) can be managed as a single subset.

Short hydration regimen with magnesium supplementation prevents cisplatin-induced nephrotoxicity in lung cancer: a retrospective analysis.

PURPOSE: The purpose of this study was to evaluate renal function in lung cancer patients who were administered cisplatin with continuous higher-volume hydration (CH) or a short hydration (SH) regimen. METHODS: We retrospectively evaluated patients with lung cancer who were treated with chemotherapy regimens including >50 mg/m2 of cisplatin between August 2007 and March 2015. Between August 2007 and December 2012, patients received a continuous higher-volume hydration regimen without magnesium (Mg) supplementation (CH group), and after May 2013, patients received a short hydration regimen with Mg supplementation (SH group). To evaluate the factors influencing serum creatinine (SCr) increase during the first course of cisplatin chemotherapy, univariate and multivariate logistic regression analyses were conducted. RESULTS: A total of 122 patients were evaluated, 62 patients in the CH group and 60 patients in the SH group. Grade 1 (National Cancer Institute Common Toxicity Criteria for Adverse Events; version 4.0) or higher SCr increases were more frequently observed in the CH group than in the SH group after the first cycle (P = 0.01, Fisher's exact test) and for all cycles (P = 0.03). Multivariate analysis revealed that short hydration (odds ratio (OR), 0.30; 95% confidence internal (CI) (0.11-0.75), P = 0.01) and estimated creatinine clearance (eCcr) of ≥70 mL/min (OR, 0.25; 95% CI (0.088-0.69), P = 0.008) were associated with a significantly reduced risk for cisplatin-induced grade 1 or higher SCr increase. CONCLUSION: Our study suggested that a short hydration method with Mg supplementation and eCcr of ≥70 mL/min reduced the risk of cisplatin-induced nephrotoxicity.