Motohiro Hirao

Patient-controlled Dietary Schedule Improves Clinical Outcome after Gastrectomy for Gastric Cancer

Although studies have shown that early oral feeding after abdominal surgery is feasible, the optimal dietary schedule has not been established. This study was conducted prospectively to compare the clinical outcome of patient-controlled dietary schedule with that of conventional dietary schedule after gastric resection for early cancer. Patients in the patient-controlled diet (PC) group (n = 53) received a solid diet on demand; patients in the conventional regimen (CR) group (n = 50) received a solid diet from postoperative day (POD) 10. All patients underwent distal gastrectomy for early gastric cancer. A liquid diet was tolerated by the PC group on POD 2, and a solid diet was taken on POD 6 after gastrectomy, earlier than in the CR group. The postoperative hospital stay was 18.5 ± 5.9 days (10–40) in the PC group, versus 21.7 ± 8.8 days (14–57) in the CR group (p = 0.02). Patients in the PC group had a higher daily oral intake of calories on POD 10 than those in the CR group (p = 0.02). Changes in body weight and serum albumin during the postoperative period and after discharge, and the incidence of complications and variances from clinical pathways did not show significant differences between the two groups. The PC schedule was feasible after distal gastrectomy for early gastric cancer. It improved the clinical outcome, with a shorter postoperative hospital stay and a higher oral energy intake on early phase, compared with the CR schedule. Moreover, the PC approach was useful for establishing the optimal dietary schedule and improving the clinical pathway.

Survival analysis of patients with duodenal gastrointestinal stromal tumors.

Goals To evaluate the survival characteristics of patients with duodenal gastrointestinal stromal tumors (GISTs). Background GISTs represent the most common mesenchymal neoplasms. However, duodenal GISTs are relatively rare, and few studies have been performed with a focus on duodenal GISTs. Study We collected the data of 41 GIST patients including 7 duodenal cases. Clinicopathologic findings and recurrence-free survival (RFS) of duodenal GIST patients were analyzed. Results The proportion of having any symptoms was 86% in duodenum, 32% in stomach, and 56% in other GISTs (P=0.034), and the most common symptoms of duodenal GISTs were melena and anemia. The 2-year RFS rates were 51.4% in duodenal GISTs, 78.4% in stomach GISTs, and 100% in other GISTs, and duodenal GISTs showed poorer RFS than nonduodenal GISTs (hazard ratio, 5.1; log-rank P=0.019). Particularly, in low-risk and intermediate-risk group, the hazard ratio of recurrence was 12.3 (log-rank P=0.010). Multivariate Cox analysis showed symptom (P=0.007), mitotic index (P=0.011), and tumor location (P=0.043) were significant prognostic factors of recurrence. Conclusions RFS of duodenal GISTs was worse than nonduodenal GISTs.

Comparison of Perioperative and Long-term Outcomes of Total and Proximal Gastrectomy for Early Gastric Cancer: A Multi-institutional Retrospective Study

BackgroundVarious surgical procedures are used to treat early gastric cancers in the upper third of the stomach (U-EGCs). However, there is no general agreement regarding the optimal surgical procedure.MethodsThe medical records of 203 patients with U-EGC were collected from 13 institutions. Surgical procedures were classified as Roux-en-Y esophagojejunostomy after total gastrectomy (TG-RY), esophagogastrostomy after proximal gastrectomy (PG-EG), or jejunal interposition after PG (PG-JI). Patient clinical characteristics and perioperative and long-term outcomes were compared among these three groups.ResultsTG-RY, PG-EG, and PG-JI were performed in 122, 49, and 32 patients, respectively. Tumors were larger in TG-RY patients than in PG-EG and PG-JI patients, and undifferentiated-type gastric adenocarcinoma tended to be more frequent in TG-RY than in PG-EG. The operative time was shorter for PG-EG than for PG-JI and TG-RY. Hospital stay and early postoperative complications were not different for the three procedures. With respect to gastrectomy-associated symptoms, a “stuck feeling” and heartburn tended to be more frequent in PG-EG patients, while dumping syndrome and diarrhea were more frequent in TG-RY patients. Post-surgical weight loss was not different among the three groups, however, serum albumin and hemoglobin levels tended to be lower in TG-RY patients.ConclusionThree surgical procedures for U-EGC did not result in differences in weight loss, but PG-EG and PG-JI were better than TG-RY according to some nutritional markers. In U-EGC, where patients are expected to have long survival times, PG-EG and PG-JI should be used rather than TG-RY.

Metallothionein Expression Correlates with the Pathological Response of Patients with Esophageal Cancer Undergoing Preoperative Chemoradiation Therapy

Immunohistochemical staining for metallothionein (MT) and p53 was performed on biopsy specimens of 30 patients with esophageal squamous cell carcinoma who had received curative resection following preoperative chemoradiation. The pathologic response to chemoradiation was a partial response in 19 cases and no change was observed in 11 cases. In 16 cases with MT-positive tumor, 10 (62.5%) showed no change. In 14 cases with MT-negative tumor, 13 (92.8%) showed partial response. In 8 patients with negative staining for p53 and MT, 7 were responders, whereas in 9 patients with positive staining for p53 and MT, 6 were nonresponders. The pathologic response was significantly associated with the prognosis (p = 0.0167). The survival rate of the responders was significantly better than that of the nonresponders. These findings suggest that MT might be a prognostic marker, and consequently we can select the patients who will benefit from preoperative chemoradiation.

Phase I and Pharmacokinetic Study of S-1 Combined with Weekly Paclitaxel in Patients with Advanced Gastric Cancer

Objective: A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer. Patients and Methods: Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m2 b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m2, depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD. Results: The MTD of paclitaxel was presumed to be 60 mg/m2, because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m2. Therefore, the RD of paclitaxel was estimated to be 50 mg/m2. The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m2. Conclusion: Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m2. This regimen could represent a novel and low toxic combination for advanced gastric cancer.

Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer

BACKGROUND Recently, several preoperative proinflammatory markers and nutritional factors such as neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) have been reported as significant predictor for poor prognosis of various malignant tumors. In this study, we evaluated the prognostic values of these preoperative parameters in patients with resectable pancreatic head cancer. METHODS We retrospectively reviewed consecutive patients who underwent PD for pancreatic head cancer between 2007 and 2012. A total of 46 patients were enrolled in this analysis. Preoperative parameters such as CRP, CA19-9, NLR and PNI at the time of presentation were recorded as well as overall survival. Cancer specific survival was assessed using Kaplan-Meier method. Univariate and multivariate Cox regression models were applied to evaluate the prognostic relevance of preoperative parameters. The correlations between CA19-9 values, NLR and pathological findings, first recurrence site were respectively reviewed. RESULTS In multivariable analysis preoperative high NLR (≧2.7) and high CA19-9 (≧230) were independent prognostic factors for poor survival (P value: 0.03 and 0.025, respectively). Kaplan-Meier survival analysis demonstrated the overall 2-year survival rate in patients with high NLR or high CA19-9 were 37.5% compared with 89.9% in patients with low NLR and low CA19-9. CONCLUSION Preoperative NLR and serum CA19-9 offer significant prognostic information associated with overall survival following PD in the patients with pancreatic head cancer.

Effect of Preoperative Immunonutrition on Body Composition in Patients Undergoing Abdominal Cancer Surgery

PurposePreoperative immunonutrition may induce changes that modulate stress responses and improve the outcome of patients undergoing abdominal cancer surgery. We evaluated the effectiveness of preoperative immunonutrition using an immune-enhancing diet product called Impact.MethodsForty patients aged 20–75 years, who were scheduled to undergo abdominal cancer surgery, were given Impact for 5 days preoperatively, at 1000 ml/day, in addition to a regular diet. We took various measurements before and after Impact administration.ResultsAll but two patients tolerated a daily intake >900 ml (mean: 924 ml). The serum retinol-binding protein level increased from 3.21 to 3.76 mg/dl and the arginine level increased from 91.9 to 112.0 mmol/ml after Impact intake. The urinary excretion of uracil increased significantly, from 57.6 to 88.9 mmol/g creatinine, as did the content of n-3 fatty acids and the n-3/n-6 ratio in membrane phospholipids from the white blood cells. These changes were not observed in the two patients who did not tolerate Impact. There was no significant improvement in clinical outcome.ConclusionsPreoperative immunonutrition was well tolerated by cancer patients. It induced structural changes in the white blood cell membranes and increased the body store of arginine and nucleotides. These effects may modulate the response to surgical stress.

An icteric type hepatocellular carcinoma with no detectable tumor in the liver: report of a case.

A 70-year-old man was admitted to our hospital with obstructive jaundice. Computed tomography revealed a tumor in the left intrahepatic bile duct extending to the common bile duct without any significant lesions in the liver. Cholangiography showed a filling defect due to an intraductal tumor. Cytology of the bile juice was negative and tumor markers were carcinoembryonic antigen 5.7 ng/ml, carbohydrate antigen 19-9 49 U/ml, α-fetoprotein 9 ng/dl, and PIVKA-II 19 200 AU/ml. With a preoperative diagnosis of hilar bile duct carcinoma, a laparotomy was performed. The common bile duct was filled with a tumor and it extended into the bilateral intrahepatic bile ducts. The intraductal tumor was removed together with the extrahepatic bile ducts. An intraoperative histological examination of the tumor showed a well-differentiated hepatocellular carcinoma. No lesions were detected in the liver by ultrasonography, palpation during the operation, or a computed tomography scan after the operation. At 1 year postoperatively, no recurrence has been seen in this patient.

Long-term outcomes after prophylactic bursectomy in patients with resectable gastric cancer: Final analysis of a multicenter randomized controlled trial

BACKGROUND Bursectomy, a traditional operative procedure to remove the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon, has been performed for serosa-positive gastric cancer in Japan and Eastern Asia. We conducted a multicenter, randomized, controlled trial to demonstrate the noninferiority of the omission of bursectomy. METHODS Between July 2002 and January 2007, 210 patients with cT2-3 gastric adenocarcinoma were randomized intraoperatively to D2 gastrectomy with or without bursectomy. The primary endpoint was overall survival (OS). We provide the results of the final analysis of the complete 5-year follow-up data. RESULTS After the median follow-up of 80 months, 5-year OS was 77.5% for the bursectomy group and 71.3% for the nonbursectomy group (2-sided P = .16 for superiority; 1-sided P = .99 for noninferiority). The hazard ratio for death in the nonbursectomy group was 1.40 (95% CI, 0.87-2.25). The 5-year recurrence-free survivals were 73.7% and 66.6% in the bursectomy and nonbursectomy groups, respectively (2-sided P = .33 for superiority; 1-sided P = .99 for noninferiority). Cox multivariate analysis revealed that bursectomy was an independent prognostic factor of good OS (P = .033). Subgroup analysis showed a trend toward improved survival after bursectomy for tumors in the middle or lower third of the stomach and for pathologically serosa-positive tumors. CONCLUSION The final analysis could not demonstrate the noninferiority of the omission of bursectomy. Bursectomy should not be abandoned as a futile procedure.

Pattern of surgical treatment for early gastric cancers in upper third of the stomach.

BACKGROUND/AIMS Various surgical treatments are indicated for early gastric cancers in upper third of the stomach (U-EGC) because of its anatomical property and favorable prognosis. METHODOLOGY Five hundred and eighty six cases of U-EGCs were collected for 9 years from 19 hospitals in Japan. Surgical procedures were classified as total (TG) and proximal gastrectomy (PG), and the latter was subclassified as esophagogastrostomy (PG-EG) and jejunal interposition (PG-JI) reconstruction. RESULTS TG was more frequent than PG (76.3% vs. 21.8%, p<0.0001). PG was more frequently performed in high volume hospitals than in low volume hospitals (26.8% vs. 10.2%, p<0.0001), however there were still large difference in frequency of PG even among high volume hospitals, ranging from 5.0% to 72.0%. For reconstruction after PG, PG-EG and PG-JI were representatively performed in 50 (39.1%) and 35 (27.3%) patients. Each institute tended to preferentially employ either PG-EG or PG-JI. Tumor size was significantly larger in TG than in PG (38.8mm vs. 22.3mm, p<0.0001) and diffuse type tended to be more frequent in TG as well. CONCLUSIONS There is a huge variety of surgical treatment for U-ECG in general hospitals in our country. A multi-institutional large cohort randomized trial might be urgent to establish the standard surgical procedure of this infrequent disease.