Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial).

BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.

Optimal Roux-en-Y reconstruction after distal gastrectomy for early gastric cancer as assessed using the newly developed PGSAS-45 scale.

PURPOSE: The optimal surgical procedure for distal gastrectomy with Roux-en-Y reconstruction (DGRY) remains to be determined. Recently, a self-report assessment instrument, the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45), was compiled to evaluate symptoms, the living status and the quality of life of patients who have undergone gastrectomy. We used this scale to evaluate procedures used for DGRY. METHODS: The subjects included 475 patients who underwent DGRY for stage IA/IB gastric cancer. We evaluated whether the size of the remnant stomach, length of the Roux limb, reconstruction route and anastomotic procedure affected the patients' symptoms, living status and quality of life assessed using the PGSAS-45. RESULTS: Patients with a residual stomach of more than half had significantly worse esophageal reflux scores than the patients with a smaller residual stomach (P = 0.0462); a residual stomach of one-third or one-fourth was favorable. A shorter length of the Roux limb was shown to be preferable to a longer Roux limb based on the results of the PGSAS-45. In addition, antecolic reconstruction and the anastomotic procedure using a linear stapler were found to be more favorable. CONCLUSIONS: The size of the remnant stomach and the length and route of the Roux limb significantly influence the patient-reported DGRY outcomes.

Evaluation of QOL after proximal gastrectomy using a newly developed assessment scale (PGSAS-45).

BACKGROUND: Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG. METHODS: In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach. RESULTS: The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre-operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had. CONCLUSION: These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL.

Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 and changes in body weight are useful tools for evaluation of reconstruction methods following distal gastrectomy.

BACKGROUND: Billroth-I (BI) and Roux-en-Y (RY) are well-known reconstruction methods that are conducted following distal gastrectomy. However, the relative merits of these 2 methods are not well documented. The newly developed Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 is an integrated questionnaire consisting of 45 items, including 8 items from the 8-Item Short-Form Health Survey (SF-8), 15 items from the Gastrointestinal Symptom Rating Scale, and 22 items selected by gastric surgeons. Postoperative QOL ratings were evaluated for each reconstruction method using PGSAS-45. METHODS: The PGSAS-45 questionnaire was distributed to 2,922 patients who underwent gastrectomies at 52 medical institutions. Among the questionnaires distributed, 2520 (86 %) were retrieved and 2368 (81 %) met eligibility requirements. Statistical analyses were conducted to compare 1,384 of the eligible questionnaires, including responses from patients who underwent BI (n = 909) and RY (n = 475) procedures. RESULTS: BI procedures were associated with significantly longer postoperative periods, a significantly greater size of gastric remnants, and a higher frequency of laparoscopic approaches and celiac branch preservation. Postoperative QOL analysis indicated that BI procedures resulted in significantly lower postoperative weight loss and significantly higher esophageal reflux symptoms than RY procedures. There was no significant difference between the two groups on other outcome measures. CONCLUSIONS: Although weight loss was significantly lower following BI procedures, esophageal reflux symptoms were significantly higher. Either BI or RY procedures may be recommended based on the individual patient's condition after distal gastrectomy. The newly developed QOL questionnaire, PGSAS-45 and changes in body weight proved useful for evaluation of QOL following gastrectomy.

D2-lymphadenectomy improves the survival of patients with peritoneal cytology-positive gastric cancer.

BACKGROUND: According to the current Japanese Classification of Gastric Cancer, patients with peritoneal cytology-positive (CY1) gastric cancer are classified as stage IV and the curative potential of resection for these patients is regarded as non-curative. MATERIALS AND METHODS: We compared the clinical outcome of CY1 patients (n=55) with those of patients with other non-curative factors (n=87), to clarify the optimal surgical strategy for CY1 patients. RESULTS: The 5-year survival rate of CY1 patients was 10.8%, which was significantly better than that observed in the patients with the other non-curative factors. Among CY1 cases, survival outcome of the patients with lymph node metastasis limited to within group 2 was significantly better than the patients with group 3 lymph node metastasis. CONCLUSION: These results suggested that gastrectomy combined with extended lymphadenectomy should be recommended for patients with gastric cancer who have positive peritoneal cytology as the only non-curative factor.

Phase II study of mitomycin C, cisplatin and 5-fluorouracil for advanced and recurrent gastric cancer.

In this study, we assessed the efficacy and feasibility of a 5-FU, MMC and cisplatin combination in patients with advanced or recurrent gastric cancer. 5-FU was administered at a dose of 360 mg/m2 on days 1 through 5 and days 8 through 12. CDDP was administered at a dose of 7 mg/m2 on days 1 through 5 and days 8 through 12. MMC was given at a dose of 13 mg/m2 on day 1. Twenty-seven patients with non-resectable or recurrent gastric cancer were entered. The most common toxicity was leukopenia. Nausea/vomiting was generally mild and no patient suffered severe diarrhea, mucositis or renal insufficiency. While a complete response was not observed, 13 patients showed a PR giving an overall response rate of 48.1% (95%CI, 28.0 to 68.3%). Our regimen may have advantages in terms of reduced toxicity with moderate efficacy that is comparable with results using the ECF regimen.

Long-term postoperative survival of a gastric cancer patient with numerous para-aortic lymph node metastases.

A56-year-old man with advanced gastric cancer was referred to our hospital. Preoperative abdominal computed tomography revealed numerous enlarged lymph nodes, including the lymph nodes of the paraaortic region. The patient underwent total gastralectomy, splenectomy, left-adrenalectomy and resection of the body and tail of the pancreas by Appleby's method, along with paraaortic lymph node dissection. Microscopic examination revealed that the tumor was a solid type, poorly differentiated adenocarcinoma, which displayed invasion of the serosal surface. There were apparently many lymph node metastases. We identified 31 cancer-positive paraaortic nodes, while the total number of lymph node metastases was 81. It was not possible to administer sufficient postoperative adjuvant chemotherapy, as the patient experienced postoperative complications, including pancreatic fistula and watery diarrhea. Despite the lack of sufficient chemotherapy, the patient has subsequently remained disease-free for 9 years and 3 months, and continues to visit our hospital as an outpatient. In conclusion, we wish to emphasize the need for a critical application of paraaortic lymph node dissection as one modality of multidisciplinary treatment in patients with advanced gastric cancer in whom paraaortic lymph node metastasis is strongly suspected preoperatively.