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.     

A novel sustained release system for aqueous cis-platinum

The authors devised a novel sustained release system for aqueous cis-platinum (CDDP) to study in vitro the degradability of the carrier materials and the release profile of the CDDP. We first prepared fibrin hydrogels with clinically used biomedical materials, and irradiated the gels with ultraviolet (UV)-rays to form gradually degradable drug carriers. We then loaded aqueous CDDP into the carriers under negative pressure. These prepared materials were incubated in fibrinolytic test medium at 37 degrees C for the in vitro studies. The UV-irradiated materials slowly degraded and dissolved within 10-15 days, while non-UV-treated carriers disintegrated in 4-5 days. Each carrier showed a sustained release of CDDP. Most of the CDDP delivered was revealed to be the protein-binding (larger than 10 kDa) form. Free-CDDP was almost nil. The antineoplastic efficacies of this new drug delivery system developed using an original technique are now being investigated.     

Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer

Background Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents. Methods Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m² dose of CDDP. Results In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18mg/m², with CDDP 3mg/m², to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16mg/m² with CDDP, 3mg/m². In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%). Conclusion The RD was determined to be TXL 14mg/m², with CDDP 3mg/m².     

Injectable drug carriers with sustained release of cis-platinum

The authors devised injectable drug carriers with sustained release of cis-platinum (CDDP). We formed the carriers using biodegradable medical materials applied clinically: namely, fibrin hydrogel clot (FC) made from tissue adhesive, and gelatin powder (Gp) for hemostasis. Two different types of carriers were prepared: plain fibrin hydrogel clots (FCs) and Gp-containing FCs. Each carrier was dehydrated and crushed into granules, then irradiated with ultraviolet (UV) rays. These modified materials were saturated with a CDDP solution to prepare CDDP-loaded injectable sol, which were incubated at 37 degrees C in our experimental fibrinolytic systems. We examined the in vitro release profile of the CDDP and antineoplastic activities with the drug delivered from the sol. The UV-treated materials gradually released the CDDP over more than 20-30 days. Non-UV-treated carriers released the drug within 3-5 days. More than 90% of the released CDDP was revealed to be a protein-binding type, which favorably inhibited the growth of cultured cancer cells. Conversely, the CDDP incubated with human plasma showed no inhibiting functions against the growth of cancer cells. Our newly devised material appears to have great potential for loco-regional cancer chemotherapy based on the principle of local drug delivery.     

Ideal Reconstruction after Total Gastrectomy by the Interposition of a Jejunal Pouch Considered by Emptying Time

To establish the ideal form of the pouch for jejunal pouch interposition reconstruction (JPI) after total gastrectomy, the postoperative gastrointestinal function and symptoms were investigated in comparison with jejunal interposition reconstruction (JI). A total of 20 patients who underwent curative surgery for gastric cancer were enrolled in this study. In the JI group (n = 9), an isoperistaltic jejunum about 40 cm in length was interposed between the esophagus and the duodenum. In the JPI group (n = 11), a proximal pouch about 15 cm in length with a 10-cm conduit was also interposed between the esophagus and the duodenum. At follow-up 6 months postoperatively, food transit was evaluated using a radiolabeled semisolid test meal. The half-emptying time was 6.9 minutes in the JI group and 46 minutes in the JPI group. The reservoir function influenced the recovery of the patients body weight and development of the serum total protein in the early postoperative period. An early half-emptying time caused dumping symptoms in JI group. In the JPI group, there were no dumping symptoms; however, extended food clearance of pouch causes postprandial symptoms such as reflux (1 patient), vomiting (2 patients), and discomfort (2 patients). In those patients with symptoms, half-emptying times were longer than 60 minutes. There was a statistically significant correlation between the pouch length and the half-emptying time of the gastric substitute in JPI group (p = 0.0039, r = 0.789). If we estimate that the appropriate half-emptying time is 20 to 60 minutes, correlation of the pouch length and the half-emptying time shows that the ideal pouch length is about 12–15 cm in JPI. In jejunal pouch interposition reconstruction after total gastrectomy, an adequate procedure leads to nutritional advantage and prevents postoperative symptoms.     

Intraperitoneal administration of a combined CDDP, 5-FU and MMC therapy for pseudomyxoma peritonei

Pseudomyxoma peritonei, which is the seeding of the peritoneum by mucin-secreting metastatic deposits and the filling of the peritoneal cavity by these secretions, is a malignancy that even after excision of the metastatic areas has a poor prognosis, since no effective therapy has yet been established. Herein, we report five cases of pseudomyxoma peritonei that responded to a combined postsurgical therapy consisting of CDDP, 5-FU and MMC. A 59-year-old women had a complete response who underwent an appendectomy, a right ovariectomy, and an omentectomy due to pseudomyxoma peritonei, and was postoperatively given a 50 mg intraperitoneal administration of CDDP. Further, a subcutaneous implant-type reservoir was positioned intraperitoneally for postoperative chemotherapy. At 14 days after surgery, therapy was begun which consisted of CDDP (70 mg/m2/day 1), 5-FU (350 mg/m2/day 1) and MMC (6 mg/m2/day 1) administered intraperitoneally, and 5-FU (350 mg/m2/day 1-3) that was continuously infused by an intravenous drip. She received 4 courses of postoperative chemotherapy. As a result of this therapy, the serum CEA values, which had elevated postoperatively, fell to within their respective normal ranges, and at 44 months postoperatively, this patient remains alive. Given the results above, intraperitoneal administrations of this combined CDDP, 5-FU, MMC therapy may be effective for patients with pseudomyxoma peritonei.     

A case of advanced gastric cancer successfully treated with TS-1/CDDP combination chemotherapy, able to maintain CR for more than two years against multiple liver metastases

INTRODUCTION: In recent years, a high success rate of combination chemotherapy with TS-1/CDDP has been reported against advanced gastric carcinoma. We, this time, experienced a case of advanced hemorrhagic gastric cancer with multiple hepatic metastases for which total gastrectomy was performed, followed by postoperative combination chemotherapy with TS-1/CDDP which culminated in achieving CR for the liver metastases. CASE REPORT: The patient was a 59-year-old woman who was hospitalized for a type IV gastric carcinoma in the upper part of the gastric body. Further examination revealed liver (S 2, S 5, S 7) and lymph node metastases. Due to hemorrhage from the tumorous lesion, the treatment strategy selected was total gastrectomy followed by postoperative chemotherapy. Operative and clinicopathological findings revealed a mass lesion of MLU, type IV, 16.0x14.0 cm, sT 3 (SE), sH 1 (bilobular multiple metastases) and CY 0, and por 1, pT 2 (SS), pN 1 (+) [23/38], int, INF beta, ly 3 and v 1, respectively. Combination chemotherapy with TS-1/CDDP was instituted after surgery. As for the dosing method of combination chemotherapy,the patient was treated with a course of TS-1 80 mg daily divided into two doses over 21 days continuously, followed by a 14-day cessation of the drug,together with a dose of CDDP 70 mg on day 8. The patient received a total of four courses. At the completion of the third chemotherapy course, her multiple hepatic metastases disappeared. Further, the preoperative CA 19-9 level of 370 U/mL returned to normal after chemotherapy. Adverse events observed were leukopenia and thrombocytopenia, both of which were judged to be grade 2. At two years and nine months, the patient is being followed on an outpatient basis without any sign of postoperative recurrent disease. CONCLUSION: We experienced a patient who was successfully treated with combination chemotherapy and demonstrated disappearance of her multiple hepatic metastases, showing a clinical response of CR lasting for more than two years against the metastases. It was inferred that this regimen of TS-1/CDDP is an effective treatment modality not only as preoperative but also postoperative chemotherapy after surgery for advanced gastric carcinoma.     

Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis

To seek for a candidate gene that would regulate tumour progression and metastasis in gastric cancer, we investigated gene expression profiles by using DNA microarray. Tumour tissue and adjacent normal tissue were obtained from 21 patients with gastric cancer and then examined for their gene expression profiles by the Gene Chip Human U95Av2 array, which includes 12 000 human genes and EST sequences. A total of 25 genes were upregulated and two genes were downregulated by at least four-fold in the tumour tissue. In a further analysis according to lymph node metastasis, the expressed levels of maspin, as well as carcinoembryonic antigen and nonspecific crossreacting antigen were significantly higher in tumours with lymph node metastasis than in those without it. Maspin expression in 85 gastric cancer patients was further investigated by using immunohistochemistry. Maspin expression was not observed in normal gastric epithelia without intestinal metaplasia. In contrast, maspin was expressed in 74 of 85 tumour tissues. There was a significant correlation between the incidence of maspin-positive tumour staining and lymph node metastasis. These results suggest that maspin has a potential role for tumour metastasis in gastric cancer.     

Catalase expression of Propionibacterium acnes may contribute to intracellular persistence of the bacterium in sinus macrophages of lymph nodes affected by sarcoidosis

Immunologic Research - Bacterial catalase is important for intracellular survival of the bacteria. This protein of Propionibacterium acnes, one of possible causes of sarcoidosis, induces...