Estimation of the physiologic ability and surgical stress scoring system as a useful predictor of postoperative recurrence in patients with stage II colorectal cancer: a multicenter study.

PURPOSE: We determined the usefulness of the estimation of physiologic ability and surgical stress (E-PASS), initially reported as a predictive factor for postoperative morbidity and mortality, as a prognostic indicator in stage II colorectal cancer (CRC). METHODS: Overall, 739 patients who underwent proctocolectomy for CRC at Tottori University Hospital and affiliated hospitals and histologically diagnosed with stage II CRC were included in the current study. RESULTS: A receiver operating characteristic (ROC) analysis of the five-year recurrence-free survival indicated that the comprehensive risk score (CRS) of E-PASS predicted postoperative recurrence. A multivariate analysis revealed that the presence of preoperative perforation, T4, v ≥ 2, and CRSHigh (≥ 0.2267) were independent predictors of postoperative recurrence. Patients were assigned a score using these factors, as follows: the presence of perforation = 1, the absence of preoperative perforation = 0, T4 = 1, T3 = 0, v2/3 = 1, v0/1 = 0, CRSHigh = 1, and CRSLow = 0 (total score: 0-4). Accordingly, the respective 5-year relapse-free survival rates were 91.0%, 83.6%, 70.3%, and 52.0% among those with scores of 0, 1, 2, and both 3 and 4 (P < 0.001). CONCLUSIONS: The CRS predicts postoperative recurrence in patients with stage II CRC.

Risk factors for recurrence in elderly patients with stage II colorectal cancer: a multicenter retrospective study.

BACKGROUND: Adjuvant chemotherapy for stage II colorectal cancer (CRC) is considered appropriate for patients with risk factors for recurrence, rather than for all patients uniformly. However, the risk factors for recurrence remain controversial, and there is limited information, especially for elderly patients. The Geriatric Nutritional Risk Index (GNRI) is widely used as a simple nutritional screening tool in the elderly and is associated with cancer prognosis and recurrence. This study aimed to investigate the risk factors for recurrence in the elderly with stage II CRC, focusing on the GNRI. METHODS: We enrolled 348 elderly patients (≥ 75 years) with stage II CRC who underwent curative resection at the Department of Surgery, Tottori University and our 10 affiliated institutions. The patients were divided into GNRIhigh (≥ 93.465) and GNRIlow (< 93.465) groups. RESULTS: The GNRIlow group showed a significantly worse overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) (P < 0.001, P < 0.001, and P < 0.001, respectively). In a multivariate analysis, GNRIlow (hazard ratio [HR]: 2.244, P < 0.001), pathologic T4 stage (HR: 1.658, P = 0.014), and moderate to severe lymphatic or venous invasion (HR: 1.460, P = 0.033) were independent factors affecting RFS. By using these three factors to score the risk of recurrence from 0 to 3 points, the prognosis was significantly stratified in terms of OS, CSS, and RFS (P < 0.001, P < 0.001, and P < 0.001, respectively). The recurrence rate for each score was as follows: 0 points, 9.8%; 1 point, 22.0%; 2 points, 37.3%; and 3 points, 61.9%. CONCLUSIONS: GNRIlow, pathologic T4 stage, and moderate to severe lymphatic or venous invasion are high-risk factors for recurrence in the elderly with stage II CRC. The scoring system using these three factors appropriately predicted their recurrence and outcome.

A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI).

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer: a randomized controlled trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer. METHODS: Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints. RESULTS: Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B. CONCLUSIONS: Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

[Long-term disease-free survival by S-1 therapy in a case of gastric cancer with peritoneal dissemination].

The patient was a 77-year-old woman who underwent gastrectomy for gastric cancer. Since the patient had positive peritoneal washing cytology and positive peritoneal dissemination, she was started on oral S-1 therapy post-surgery for 4 weeks, followed by a 2-week rest period. During the first course of therapy, her white blood cell count decreased; therefore, the regimen was changed to a 1-week administration, followed by a 1-week rest period. No subsequent adverse events were noted. The patient has experienced no relapse in the four years she has been followed up after surgery in our outpatient clinic. We report our experience with an elderly patient for whom S-1 monotherapy was effective in the treatment of gastric cancer with peritoneal dissemination.

Characteristics of sarcopenia after distal gastrectomy in elderly patients.

Presence of preoperative sarcopenia is a risk factor for postoperative complications. However, there are few reports on the presence of sarcopenia and its characteristics following gastrectomy. Sarcopenia is closely related to quality of life in elderly people. To date, the main purpose of follow-up after gastrectomy is surveillance for early detection of recurrence and secondary cancer. However, henceforth, quality of life in elderly gastric cancer patients after gastrectomy must also be evaluated. The present study aimed to investigate sarcopenia during a 1-year postoperative course in elderly gastric cancer patients and examine their characteristics. The subjects were 50 patients aged ≥70 years who underwent laparoscopy-assisted distal gastrectomy for gastric cancer and who experienced no recurrence 1 year postoperatively. Height, weight, serum albumin levels, food intake amount, grip strength, gait speed, visceral fat area, and appendicular skeletal muscle mass index were measured preoperatively and 6 months and 1 year postoperatively. Sarcopenia, obesity, and visceral obesity were diagnosed. Compared with preoperatively, indicators other than height decreased 6 months postoperatively. Compared with 6 months postoperatively, body weight, amount of food intake, and visceral fat area increased by 1 year postoperatively, unlike appendicular skeletal muscle mass index. The frequency of sarcopenia increased 6 months postoperatively compared with preoperatively; this frequency remained almost unchanged 1 year postoperatively compared with 6 months postoperatively. Further, the frequency of visceral obesity increased 1 year postoperatively compared with 6 months postoperatively. Weight increased after > 6 months postoperatively; however, most of the weight increase was in terms of fat and not muscle. We emphasize the importance of considering postoperative sarcopenia and visceral obesity. In particular, sarcopenia and visceral obesity should be carefully monitored after increases in body mass index and food consumption.

Internal supravesical hernia repaired via the anterior approach alone: A case report.

INTRODUCTION: Internal supravesical hernia is one of the rarest types of inguinal hernia. The hernial orifice is surrounded by the transverse vesical fold, median umbilical fold, and medial umbilical fold. PRESENTATION OF CASE: A 75-year-old male presented with lower abdominal pain and nausea. Plain abdominal CT showed that the bladder was suppressed by small bowel near the left internal inguinal ring. A part of the small bowel wall seemed to be inlaid, and so the patient was diagnosed with a strangulated left inguinal hernia. The hernia repair operation was performed via the anterior approach. There was no internal hernial sac found, but there was a walnut-sized mass in the properitoneal space. A diagnosis was made intraoperatively of internal supravesical hernia with strangulated small bowel. Small bowel resection and hernial orifice closure were performed. DISCUSSION: Although internal supravesical hernia can present with distinctive CT findings, preoperative diagnosis is extremely difficult. Internal supravesical hernia in previous reports has been repaired via open laparotomy or laparoscopic surgery; however, we successfully repaired this intraoperatively-diagnosed internal supravesical hernia by the anterior approach alone. CONCLUSION: The patient with internal supravesical hernia diagnosed intraoperatively could be treated via the anterior approach alone successfully. Depending on the situation, the anterior approach can be an option.

Responses of cytokines and coagulation-fibrinolytic states to surgical stress following esophagectomy.

BACKGROUND/AIMS: Surgery for esophageal cancer is one of the most invasive treatments in gastrointestinal surgery. The aim of this study was to analyze perioperative kinetics of coagulation-fibrinolytic states in comparison with cytokines in order to investigate biological responses to surgical stress in patients undergoing esophagectomy. METHODOLOGY: Serum or plasma samples of 20 patients with esophageal cancer who had undergone esophagectomy were collected during the perioperative period. Serial concentrations of cytokines (IL-6, IL-8, IL-10), PMN-E, and coagulation-fibrinolytic agents (TAT and PIC) were measured and analyzed. RESULTS: There were significant increases in concentrations of both inflammatory and anti-inflammatory cytokines during the operative and postoperative courses. TAT and PIC levels also increased significantly intra- and postoperatively. The TAT/PIC ratio was elevated simultaneously with a predominance of inflammatory cytokines over anti-inflammatory ones. CONCLUSIONS: In addition to the profile of cytokines, the TAT/PIC ratio seems to be a sensitive and useful indicator in evaluating biological responses to surgical stress.

Bcl-2 and Bax expression for hepatocellular apoptosis in a murine endotoxin shock model.

BACKGROUND/AIMS: Endotoxin-induced liver failure is characterized by necrosis and apoptosis of hepatocytes. The aim of this study was to establish the relation of the time-course of hepatic parenchymal cell apoptosis and necrosis in a murine endotoxin shock model and to characterize the role of the gene products of Bcl-2 and Bax in endotoxin-mediated hepatocellular apoptosis. METHODOLOGY: Male Wistar rats were treated with 5 mg/kg body weight endotoxin, and the necrosis and apoptosis of hepatocytes were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and enzyme-linked immunosorbent assay for DNA fragmentation. Furthermore, Bcl-2 and Bax were analyzed by Western blotting. RESULTS: Endotoxin treatment led to liver dysfunction, and increased hepatic parenchymal cell apoptosis. Necrotic changes in hepatic tissues were found after the appearance of apoptosis. The apoptotic index increased up to 12 hours after endotoxin treatment. Western blot analysis revealed that the apoptosis was accompanied by a decrease of Bcl-2 protein and a relative increase of Bax protein. The apoptotic index decreased at 24 hours after the treatment synchronously with an increase in the ratio of Bcl-2 and Bax. CONCLUSIONS: These results demonstrate a significant role of hepatocellular apoptotic processes in the later development of necrosis in the liver. The kientics of this apoptosis are directly proportionate to the disturbed ratio of Bcl-2 and Bax.